bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy
Authors: Assumpção José Antônio Fagundes , Pasquarelli-do-Nascimento Gabriel , Duarte Mariana Saldanha Viegas , Bonamino Martín Hernan , Magalhães Kelly Grace 
Published: February 2022

AbstractObesity is nowadays considered a pandemic which prevalence’s has been steadily increasingly in western countries. It is a dynamic, complex, and multifactorial disease which propitiates the development of several metabolic and cardiovascular diseases, as well as cancer. Excessive adipose tissue has been causally related to cancer progression and is a preventable risk factor for overall and cancer-specific survival, associated with poor prognosis in cancer patients. The onset of obesity features a state of chronic low-grade inflammation and secretion of a diversity of adipocyte-derived molecules (adipokines, cytokines, hormones), responsible for altering the metabolic, inflammatory, and immune landscape. The crosstalk between adipocytes and tumor cells fuels the tumor microenvironment with pro-inflammatory factors, promoting tissue injury, mutagenesis, invasion, and metastasis. Although classically established as a risk factor for cancer and treatment toxicity, recent evidence suggests mild obesity is related to better outcomes, with obese cancer patients showing better responses to treatment when compared to lean cancer patients. This phenomenon is termed obesity paradox and has been reported in different types and stages of cancer. The mechanisms underlying this paradoxical relationship between obesity and cancer are still not fully described but point to systemic alterations in metabolic fitness and modulation of the tumor microenvironment by obesity-associated molecules. Obesity impacts the response to cancer treatments, such as chemotherapy and immunotherapy, and has been reported as having a positive association with immune checkpoint therapy. In this review, we discuss obesity’s association to inflammation and cancer, also highlighting potential physiological and biological mechanisms underlying this association, hoping to clarify the existence and impact of obesity paradox in cancer development and treatment.
Diabetes and restenosis
Authors: Wilson Scott , Mone Pasquale , Kansakar Urna , Jankauskas Stanislovas S. , Donkor Kwame , Adebayo Ayobami , Varzideh Fahimeh , Eacobacci Michael , Gambardella Jessica , Lombardi Angela , Santulli Gaetano 
Published: February 2022

AbstractRestenosis, defined as the re-narrowing of an arterial lumen after revascularization, represents an increasingly important issue in clinical practice. Indeed, as the number of stent placements has risen to an estimate that exceeds 3 million annually worldwide, revascularization procedures have become much more common. Several investigators have demonstrated that vessels in patients with diabetes mellitus have an increased risk restenosis. Here we present a systematic overview of the effects of diabetes on in-stent restenosis. Current classification and updated epidemiology of restenosis are discussed, alongside the main mechanisms underlying the pathophysiology of this event. Then, we summarize the clinical presentation of restenosis, emphasizing the importance of glycemic control in diabetic patients. Indeed, in diabetic patients who underwent revascularization procedures a proper glycemic control remains imperative.
Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer
Authors: Wang Fang , Li Jingruo , Li Lin , Chen Zhuo , Wang Nan , Zhu Mingzhi , Mi Hailong , Xiong Youyi , Guo Guangcheng , Gu Yuanting 
Published: February 2022

AbstractBackgroundBreast cancer (BC) threatens the health of women around the world. Researchers have proved that hsa_circ_0005505 (circ_IRAK3) facilitates BC cell invasion and migration, but the regulatory mechanisms of circ_IRAK3 in BC remain mostly unknown. We aim to explore a new mechanism by which circ_IRAK3 promotes BC progression.MethodsLevels of circ_IRAK3, microRNA (miR)-603, and kinesin family member 2A (KIF2A) mRNA in BC tissues and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, colony formation, and proliferation of BC cells were evaluated by flow cytometry, plate clone, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays. The migration, invasion, and apoptosis of BC cells were determined by transwell or flow cytometry assays. Several protein levels were detected using western blotting. The targeting relationship between circ_IRAK3 or KIF2A and miR-603 was verified via dual-luciferase reporter assay. The role of circ_IRAK3 in vivo was verified by xenograft assay.ResultsWe observed higher levels of circ_IRAK3 in BC tissues and cell lines than their respective controls. Functional experiments presented that circ_IRAK3 silencing induced BC cell apoptosis, curbed cell proliferation, migration, and invasion in vitro, and decreased tumor growth in vivo. Mechanistically, circ_IRAK3 could modulate kinesin family member 2A (KIF2A) expression through acting as a microRNA (miR)-603 sponge. miR-603 silencing impaired the effects of circ_IRAK3 inhibition on the malignant behaviors of BC cells. Also, the repressive effects of miR-603 mimic on the malignant behaviors of BC cells were weakened by KIF2A overexpression.Conclusionscirc_IRAK3 exerted a promoting effect on BC progression by modulating the miR-603/KIF2A axis, providing a piece of novel evidence for circ_IRAK3 as a therapeutic target for BC.
Dry-season transmission and determinants of Plasmodium infections in Jawi district, northwest Ethiopia
Authors: Amare Andualem , Eshetu Tegegne , Lemma Wossenseged 
Published: February 2022

AbstractBackgroundMalaria remains a serious global public health problem, and continues to have a devastating impact on people’s health worldwide. Continuous monitoring and evaluation of current malaria transmission status in different seasons is a mainstay for the success of ongoing intervention strategies for malaria. The purpose of this study was to assess the dry-season transmission and determinants of malaria in Jawi district, northwest Ethiopia.MethodsA community-based cross-sectional study was conducted from January 13 to February 11, 2020; among selected Kebeles in the Jawi district. A multistage sampling technique was used in this study. Random and systematic sampling techniques were carried out to selectKebelesand each household, respectively. Light microscopy and CareStart™ Malaria HRP2/pLDH (Pf/Pv) Combo RDT were implemented to determine the prevalence of malaria. Moreover, associated risk factors in the prevalence of malaria were assessed by using a bivariate and multivariate logistic regression model.ResultsA total of 219 study participants were enrolled in this study. Of the total enrolled individuals, malaria cases were found among 36 individuals with a positivity rate of 16.4% (95% CI 11.4–21.5).Plasmodium falciparumwas the predominant species with an estimated prevalence of 87.0% in the study areas. Interrupted utilization of ITN (AOR = 4.411, 95% CI 1.401–13.880), using over 3 years older ITNs (AOR = 9.622, 95% CI 1.881–49.214), travel history (AOR = 12.703, 95% CI 2.441–66.114), living in a house with holes on the wall (AOR = 3.811, 95% CI 1.010–14.384), and living in a house with an eave (AOR = 4.23, 95% CI 1.065–16.801) significantly increased the probability of malaria positivity rate.ConclusionMalaria is still an important public health burden among individuals in the Jawi district. Interrupted utilization of ITNs, using over 3 years older ITNs, living in a house with holes on the wall, living in a house with an eave, and travel history were identified as the risk factors of malaria. Therefore, the District health office and Health extension workers should promote daily utilization of good ITNs and improve housing conditions to reduce malaria prevalence.
The impact of Covid-19 on malaria services in three high endemic districts in Rwanda: a mixed-method study
Authors: Hakizimana Dieudonne , Ntizimira Christian , Mbituyumuremyi Aimable , Hakizimana Emmanuel , Mahmoud Hani , Birindabagabo Pascal , Musanabaganwa Clarisse , Gashumba Diane 
Published: February 2022

Abstract
Background
Rwanda has achieved impressive reductions in malaria morbidity and mortality over the past two decades. However, the disruption of essential services due to the current Covid-19 pandemic can lead to a reversal of these gains in malaria control unless targeted, evidence-based interventions are implemented to mitigate the impact of the pandemic. The extent to which malaria services have been disrupted has not been fully characterized. This study was conducted to assess the impact of Covid-19 on malaria services in Rwanda.

Methods
A mixed-methods study was conducted in three purposively selected districts in Rwanda. The quantitative data included malaria aggregated data reported at the health facility level and the community level. The data included the number of malaria tests, uncomplicated malaria cases, severe malaria cases, and malaria deaths. The qualitative data were collected using focus group discussions with community members and community health workers, as well as in-depth interviews with health care providers and staff working in the malaria programme. Interrupted time series analysis was conducted to compare changes in malaria presentations between the pre-Covid-19 period (January 2019 to February 2020) and Covid-19 period (from March 2020 to November 2020). The constant comparative method was used in qualitative thematic analysis.

Results
Compared to the pre-Covid-19 period, there was a monthly reduction in patients tested in health facilities of 4.32 per 1000 population and a monthly increase in patients tested in the community of 2.38 per 1000 population during the Covid-19 period. There was no change in the overall presentation rate for uncomplicated malaria. The was a monthly reduction in the proportion of severe malaria of 5.47 per 100,000 malaria cases. Additionally, although healthcare providers continued to provide malaria services, they were fearful that this would expose them and their families to Covid-19. Covid-19 mitigation measures limited the availability of transportation options for the community to seek care in health facilities and delayed the implementation of some key malaria interventions. The focus on Covid-19-related communication also reduced the amount of health information for other diseases provided to community members.

Conclusion
The Covid-19 pandemic resulted in patients increasingly seeking care in the community and poses challenges to maintaining delivery of malaria services in Rwanda. Interventions to mitigate these challenges should focus on strengthening programming for the community and home-based care models and integrating malaria messages into Covid-19-related communication. Additionally, implementation of the interrupted interventions should be timed and overlap with the malaria transmission season to mitigate Covid-19 consequences on malaria.
Protothecosis in the mucosa of the pharynx mimicking pharyngeal cancer in an immunocompetent individual: a case report
Authors: Yamashita Marie , Ikeda Mahoko , Kato Ito , Ohama Yuki , Ando Mizuo , Ikemura Masako , Jubishi Daisuke , Kanno Yoshiaki , Okamoto Koh , Umeyama Takashi , Nakamura Shigeki , Miyazaki Yoshitsugu , Okugawa Shu , Moriya Kyoji 
Published: February 2022

Abstract
Background
Protothecosis is a rare infection in humans and animals caused by the achlorophyllic algae Prototheca species. More than half of the protothecosis cases are cutaneous infections, and most cases are observed in immunocompromised individuals.

Case presentation
We report a case of Prototheca wickerhamii infection in the mucosa of the pharynx in a 53-year-old immunocompetent woman with an incidentally found mass lesion at the left tongue base. Histopathological findings of the mass lesion suggested cryptococcosis, but P. wickerhamii was identified from the oropharynx scrape culture based on DNA sequencing. After surgical resection, fosfluconazole treatment was initiated, and subsequently, treatment was switched to topical amphotericin B. The residual mass lesion did not deteriorate during the 4-month antifungal treatment and 1-year observational period.

Conclusions
Prototheca species can be easily misdiagnosed as yeasts because of their morphological and pathological similarities. Prototheca, in addition to Cryptococcus should be considered if slow-growing, large Gram-positive organisms are encountered. Lactophenol cotton blue staining of the colony helps distinguish these organisms. Further study is needed to determine the appropriate treatment according to the infection focus.
Exosomal circLPAR1 functions in colorectal cancer diagnosis and tumorigenesis through suppressing BRD4 via METTL3–eIF3h interaction
Authors: Zheng Rui , Zhang Ke , Tan Shanyue , Gao Fang , Zhang Yajie , Xu Wenxia , Wang Huabin , Gu Dongying , Zhu Lingjun , Li Shuwei , Chu Haiyan , Zhang Zhengdong , Liu Lingxiang , Du Mulong , Wang Meilin 
Published: February 2022

Abstract
Background
Exosomes have emerged as vital biomarkers of multiple cancers and contain abundant circular RNAs (circRNAs). However, the potential for exosomal circRNAs to be used in diagnostics and their molecular mechanism of action in colorectal cancer (CRC) remain unclear.

Methods
CRC-specific exosomal circRNAs were identified by RNA sequencing, exoRBase database and a tissue microarray. The diagnostic performance of plasma exosomal circRNAs was evaluated among cancer-free controls, precancer individuals, CRC patients, and patients with other types of cancer. The corresponding biological functions were mainly assessed using circRNA pull-down, proteomic analysis, and RNA immunoprecipitation assay underlying cellular and mouse models.

Results
CircLPAR1 was encapsulated in exosomes with high stability and detectability, and its expression in plasma exosomes was remarkably decreased during CRC development but recovered after surgery. Exosomal circLPAR1 showed cancer specificity in CRC diagnosis and increased the diagnostic performance to an area under the receiver operating characteristic curve of 0.875, as determined by analysing its performance in combination with common clinical biomarkers CEA and CA19–9. Additionally, circLPAR1 was downregulated in CRC tissues and was associated with overall survival. Mechanistically, exosomal circLPAR1 was internalized by CRC cells, and it suppressed tumor growth, likely because exosomal circLPAR1 directly bound with eIF3h specifically suppressed the METTL3-eIF3h interaction, decreasing the translation of oncogene BRD4.

Conclusions
This comprehensive study highlights plasma exosomal circLPAR1 as a promising predictor in CRC diagnosis and describes its biological regulation of colorectal tumorigenesis. This study provides a new perspective on early diagnosis in the clinic and pathogenesis in disease development.
m6A modification: recent advances, anticancer targeted drug discovery and beyond
Authors: Deng Li-Juan , Deng Wei-Qing , Fan Shu-Ran , Chen Min-Feng , Qi Ming , Lyu Wen-Yu , Qi Qi , Tiwari Amit K. , Chen Jia-Xu , Zhang Dong-Mei , Chen Zhe-Sheng 
Published: February 2022

AbstractAbnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs.

Graphical abstract
Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.
METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis
Authors: Fan Hui-Ning , Chen Zhao-Yu , Chen Xiao-Yu , Chen Ming , Yi You-Cai , Zhu Jin-Shui , Zhang Jing 
Published: February 2022

AbstractBackgroundN6-methyladenosine (m6A) RNA methylation and circular RNAs (circRNAs) have been shown to act vital roles in multiple malignancies including gastric cancer (GC). However, there is little knowledge about how m6A modification of circRNAs contributes to GC progression.MethodsThe association of METTL14 expression with the clinicopathological characteristics and prognosis in patients with GC was assessed by Western blot, Immunohistochemistry and public datasets. In vitro and vivo function experiments were conducted to investigate the role of METTL14 in GC. Furthermore, m6A-circRNA epitranscriptomic microarray was utilized to identify METTL14-mediated m6A modification of circRNAs, which were validated by methylated RNA immunoprecipitation (Me-RIP), RT-qPCR and rescue experiments in GC cells. The sponge of circORC5 with miR-30c-2-3p was confirmed by luciferase gene report and RNA immunoprecipitation assays. The expression, localization and prognosis of circORC5 in GC were evaluated by fluorescence in situ hybridization. The effects of METTL14 and (or) circORC5 on miR-30c-2-3p-mediated AKT1S1 and EIF4B were estimated by RT-qPCR and Western blot analyses.ResultsWe found that METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC. Ectopic expression of METTL14 markedly repressed growth and invasion of GC cellsin vitroandin vivo, whereas knockdown of METTL14 harbored the opposite effects. Mechanically, m6A-circRNA epitranscriptomic microarray and Me-RIP identified circORC5 as the downstream target of METTL14. Silencing of METTL14 reduced the m6A level of circORC5, but increased circORC5 expression. Moreover, circORC5 could sponge miR-30c-2-3p, and reverse METTL14-caused upregulation of miR-30c-2-3p and downregulation of AKT1S1 and EIF4B. In addition, circORC5 possessed a negative correlation with miR-30c-2-3p and indicated a poor survival in GC.ConclusionOur findings demonstrate that METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis.
The effects and mechanism of paeoniflorin in promoting osteogenic differentiation of MC3T3-E1
Authors: Guo Wei , Yang Xiao-guang , Shi Yu-lin , Wang Hong 
Published: February 2022

Abstract
Background
The incidence of osteoporosis and osteoporotic fractures is increasing every year. Traditional Chinese Medicine (TCM) can shed new light on the treatment of osteoporosis. This study aimed to explore the role and mechanism of paeoniflorin in promoting osteogenic differentiation of an osteoblast precursor cell line (MC3T3-E1).

Methods
MC3T3-E1 cells were cultured in osteogenic induction medium (OIM) and OIM combined with different concentrations of paeoniflorin. The optimal dose of paeoniflorin was assessed by a cell counting kit-8 (CCK-8) assay. Then, alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining were performed to assess the osteogenic capacity of paeoniflorin. The transcription of osteogenic genes and the expression of osteogenic proteins were assessed by RT-PCR and Western blotting, respectively. The transcription of Wnt/β-catenin signaling pathway genes and proteins was assessed by RT-PCR and Western blotting, respectively. Finally, Dickkopf-1 (DKK-1), a Wnt/β-catenin signaling pathway inhibitor, was used to identify whether the Wnt/β-catenin signaling pathway was involved in the osteogenic differentiation of paeoniflorin. Osteoclastogenesis in RAW264.7 cells was identified by tartrate-resistant acid phosphatase (TRAP) staining.

Results
At concentrations ranging from 0.1 to 100 μM, paeoniflorin was not cytotoxic to MC3T3-E1 cells. Paeoniflorin significantly increased the osteogenic differentiation of MC3T3-E1 cells in a dose-dependent manner. Moreover, paeoniflorin significantly increased osteogenic differentiation gene and protein expression. Through bioinformatic analysis, paeoniflorin-affected genes were found to be involved in different signaling pathways, such as the Wnt/β-catenin signaling pathway. Paeoniflorin enhanced β-catenin and CyclinD1 expression compared with that of the control groups. DKK-1 partially reversed the promoting effects of paeoniflorin in promoting osteogenic differentiation of MC3T3-E1 cells. Moreover, paeoniflorin inhibited the osteoclastogenesis of RAW264.7 cells.

Conclusion
Paeoniflorin promotes osteogenic differentiation in MC3T3-E1 cells by regulating the Wnt/β-catenin pathway. Paeoniflorin is a potential therapeutic agent for the treatment of osteoporosis.