bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of ultra-rapid real-time PCR for detection and prevalence of Rickettsia spp. in ticks
Authors: Truong A-Tai , Yun Bo-Ram , Yoo Mi-Sun , Lim Jiyeon , Min Subin , Yoon Soon-Seek , Yun Young-Min , Kim Jong-Taek , Cho Yun Sang 
Published: May 2022

AbstractBackgroundRickettsiaspp. are important tick-borne pathogens that cause various human and animal diseases worldwide. A tool for rapid and accurate detection of the pathogens from its vectors is necessary for prevention of Rickettsioses propagation in humans and animals, which are infested by ticks. Therefore, this study was conducted to evaluate a molecular tool, ultra-rapid real-time PCR (UR-qPCR), for rapid and accurate detection ofRickettsiaspp. from 5644 ticks in 408 pools collected from livestock and their surrounding environments in Gangwon and Jeju province in South Korea.ResultsThe UR-qPCR ofRickettsiaDNA showed a limit of detection of 2.72 × 101copies ofRickettsiaDNA and no cross reaction with other tick-borne pathogens, namelyAnaplasma phagocytophilum,Ehrlichia chaffeensis,E. canis,Toxoplasma gondii, andBorrelia burgdorferi. In addition, the PCR assay also showed possibility of variousRickettsiaspecies detection includingR. monacensis,“CandidatusR. longicornii”, R. japonica, R. roultii,andR. tamurae.The collected ticks were identified with major species belonged toHaemaphysalis longicornis(81.62%), followed byH. flava(15.19%),andIxodes nipponensis(3.19%).Rickettsiadetection from tick samples using the UR-qPCR showed that the minimum infection rate (MIR) ofRickettsiain collected ticks was 1.24‰ and that all positive pools containedH. longicornis,equal to the MIR of 1.39‰ of this species. Additionally, MIR ofRickettsiaspp. detected in ticks collected in Gangwon and Jeju was 1.53‰ and 0.84‰, respectively. Furthermore, the sequencing results of the 17 kDa protein antigen gene andompAgene showed thatRickettsiaspp. sequences from all pools were related to “CandidatusR. longicornii” and “CandidatusR. jingxinensis”.ConclusionsThe UR-qPCR system was demonstrated to be useful tool for accurate and rapid detection ofRickettsiafrom its vector, ixodid ticks, within 20 min. The data onRickettsiaspp. in ticks detected in this study provide useful information on the distribution ofRickettsiain previously unstudied Korean provinces, which are important for the prevention and control of the spread of rickettsioses in both animals and humans in the country.
Predicting EGFR mutation, ALK rearrangement, and uncommon EGFR mutation in NSCLC patients by driverless artificial intelligence: a cohort study
Authors: Tan Xueyun , Li Yuan , Wang Sufei , Xia Hui , Meng Rui , Xu Juanjuan , Duan Yanran , Li Yan , Yang Guanghai , Ma Yanling , Jin Yang 
Published: May 2022

Abstract
Background
Timely identification of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement status in patients with non-small cell lung cancer (NSCLC) is essential for tyrosine kinase inhibitors (TKIs) administration. We aimed to use artificial intelligence (AI) models to predict EGFR mutations and ALK rearrangement status using common demographic features, pathology and serum tumor markers (STMs).

Methods
In this single-center study, demographic features, pathology, EGFR mutation status, ALK rearrangement, and levels of STMs were collected from Wuhan Union Hospital. One retrospective set (N = 1089) was used to train diagnostic performance using one deep learning model and five machine learning models, as well as the stacked ensemble model for predicting EGFR mutations, uncommon EGFR mutations, and ALK rearrangement status. A consecutive testing cohort (n = 1464) was used to validate the predictive models.

Results
The final AI model using the stacked ensemble yielded optimal diagnostic performance with areas under the curve (AUC) of 0.897 and 0.883 for predicting EGFR mutation status and 0.995 and 0.921 for predicting ALK rearrangement in the training and testing cohorts, respectively. Furthermore, an overall accuracy of 0.93 and 0.83 in the training and testing cohorts, respectively, were achieved in distinguishing common and uncommon EGFR mutations, which were key evidence in guiding TKI selection.

Conclusions
In this study, driverless AI based on robust variables could help clinicians identify EGFR mutations and ALK rearrangement status and provide vital guidance in TKI selection for targeted therapy in NSCLC patients.
Sodium‑glucose co-transporter‑2 inhibitors in the treatment of diabetes with heart failure
Authors: Liang Bo , Gu Ning 
Published: May 2022

Abstract2022 AHA/ACC/HFSA guideline for the management of heart failure, which is valuable for clinical decision-making, was recently released. This guideline recommended patients with heart failure with type 2 diabetes sodium‑glucose co-transporter‑2 inhibitors for the management of hyperglycemia and to reduce heart failure-related morbidity and mortality (Class 1, Level A). It is important to note that the source of evidence based on this recommendation is from EMPEROR-Reduced, DAPA-HF, and DECLARE-TIMI 58 and does not include newly published PRESERVED-HF, CHIEF-HF, and EMPEROR-Preserved. Here we reviewed these important trials in order to provide more clinical references for patients with diabetes and heart failure, especially heart failure with preserved ejection fraction.
The circSPON2/miR-331-3p axis regulates PRMT5, an epigenetic regulator of CAMK2N1 transcription and prostate cancer progression
Authors: Yao Bing , Zhu Sha , Wei Xiyi , Chen Ming-Kun , Feng Yangkun , Li Zhimin , Xu Xinyu , Zhang Yuwei , Wang Yang , Zhou Jingwan , Tang Ningyuan , Ji Chengjian , Jiang Peng , Zhao Shan-Chao , Qin Chao , Feng Ninghan 
Published: May 2022

Abstract
Background
Prostate cancer (PCa) is the most frequently diagnosed malignancy in men, and its mechanism remains poorly understood. Therefore, it is urgent to discover potential novel diagnostic biomarkers and therapeutic targets that can potentially facilitate the development of efficient anticancer strategies.

Methods
A series of functional in vitro and in vivo experiments were conducted to evaluate the biological behaviors of PCa cells. RNA pulldown, Western blot, luciferase reporter, immunohistochemistry and chromatin immunoprecipitation assays were applied to dissect the detailed underlying mechanisms. High-throughput sequencing was performed to screen for differentially expressed circRNAs in PCa and adjacent normal tissues.

Results
Upregulation of protein arginine methyltransferase 5 (PRMT5) is associated with poor progression-free survival and the activation of multiple signaling pathways in PCa. PRMT5 inhibits the transcription of CAMK2N1 by depositing the repressive histone marks H4R3me2s and H3R8me2s on the proximal promoter region of CAMK2N1, and results in malignant progression of PCa both in vitro and in vivo. Moreover, the expression of circSPON2, a candidate circRNA in PCa tissues identified by RNA-seq, was found to be associated with poor clinical outcomes in PCa patients. Further results showed that circSPON2 induced PCa cell proliferation and migration, and that the circSPON2-induced effects were counteracted by miR-331-3p. Particularly, circSPON2 acted as a competitive endogenous RNA (ceRNA) of miR-331-3p to attenuate the repressive effects of miR-331-3p on its downstream target PRMT5.

Conclusions
Our findings showed that the epigenetic regulator PRMT5 aggravates PCa progression by inhibiting the transcription of CAMK2N1 and is modulated by the circSPON2/miR-331-3p axis, which may serve as a potential therapeutic target for patients with aggressive PCa.
Intermittent fasting reduces neuroinflammation in intracerebral hemorrhage through the Sirt3/Nrf2/HO-1 pathway
Authors: Dai Shuhui , Wei Jialiang , Zhang Hongchen , Luo Peng , Yang Yuefan , Jiang Xiaofan , Fei Zhou , Liang Wenbin , Jiang Jianli , Li Xia 
Published: May 2022

Abstract
Background
Inflammation contributes to the poor prognosis of intracerebral hemorrhage (ICH). Intermittent fasting (IF) has been shown to be protective against inflammation in multiple pathogenic processes. In the present study, we aimed to investigated the beneficial effects of IF in attenuating neuroinflammation and neurological deficits in a mouse model of ICH and to investigate the underlying mechanism.

Methods
ICH was modeled by intrastriatal injection of autologous blood and IF was modeled by every-other-day feeding in male control mice (C57BL/6), mice with and microglia specific knockout Sirt3f/f;Cx3cr1-Cre (Sirt3 cKO), and Sirt3f/f (wild-type) mice. Brain tissues and arterial blood were harvested at 1, 3, 7 and 28 days after ICH for immunohistochemistry analysis of Iba-1, DARPP-32 and HO-1, morphological analysis by HE staining and inflammatory factor release tests by ELISA. Neurological functions were approached by corner test and cylinder test. Fluorescent double-labeled staining of Iba-1 with CD16, Arg1 or Sirt3 was used to provide direct image of co-expression of these molecules in microglia. TUNEL, cleaved caspase-3 and Nissl staining was performed to evaluate cellular injuries.

Results
IF alleviated neurological deficits in both acute and chronic phases after ICH. Morphologically, IF enhanced hematoma clearance, reduced brain edema in acute phase and attenuated striatum atrophy in chronic phase. In addition, IF decreased the numbers of TUNEL+ cells and increased Nissl+ neuron number at day 1, 3 and 7 after ICH. IF suppressed CD16+Iba-1+ microglia activation at day 3 after ICH and reduced inflammatory releases, such as IL-1β and TNF-α. The above effects of IF were attenuated by microglia Sirt3 deletion partly because of an inhibition of Nrf2/HO-1 signaling pathway. Interestingly, IF increased Iba-1+ microglia number at day 7 which mainly expressed Arg1 while decreased the proinflammatory factor levels. In mice with microglia-specific Sirt3 deletion, the effects of IF on Iba-1+ microglia activation and anti-inflammatory factor expressions were attenuated when compared with wild-type Sirt3f/f mice.

Conclusions
IF protects against ICH by suppressing the inflammatory responses via the Sirt3/Nrf2/HO-1 pathway.
Strawberry notch homolog 2 regulates the response to interleukin-6 in the central nervous system
Authors: Syme Taylor E. , Grill Magdalena , Hayashida Emina , Viengkhou Barney , Campbell Iain L. , Hofer Markus J. 
Published: May 2022

AbstractBackgroundThe cytokine interleukin-6 (IL-6) modulates a variety of inflammatory processes and, context depending, can mediate either pro- or anti-inflammatory effects. Excessive IL-6 signalling in the brain is associated with chronic inflammation resulting in neurodegeneration. Strawberry notch homolog 2 (Sbno2) is an IL-6-regulated gene whose function is largely unknown. Here we aimed to address this issue by investigating the impact ofSbno2disruption in mice with IL-6-mediated neuroinflammation.MethodsMice with germline disruption ofSbno2(Sbno2−/−) were generated and crossed with transgenic mice with chronic astrocyte production of IL-6 (GFAP-IL6). Phenotypic, molecular and transcriptomic analyses were performed on tissues and primary cell cultures to clarify the role of SBNO2 in IL-6-mediated neuroinflammation.ResultsWe foundSbno2−/−mice to be viable and overtly normal. By contrast GFAP-IL6 ×Sbno2−/−mice had more severe disease compared with GFAP-IL6 mice. This was evidenced by exacerbated neuroinflammation and neurodegeneration and enhanced IL-6-responsive gene expression. Cell culture experiments on primary astrocytes fromSbno2−/−mice further showed elevated and sustained transcript levels of a number of IL-6 stimulated genes. Notably, despite enhanced disease in vivo and gene expression both in vivo and in vitro, IL-6-stimulated gp130 pathway activation was reduced whenSbno2is disrupted.ConclusionBased on these results, we propose a role for SBNO2 as a novel negative feedback regulator of IL-6 that restrains the excessive inflammatory actions of this cytokine in the brain.
Melatonin, an endogenous hormone, modulates Th17 cells via the reactive-oxygen species/TXNIP/HIF-1α axis to alleviate autoimmune uveitis
Authors: Huang Jun , Li Zhuang , Hu Yunwei , Li Zuoyi , Xie Yanyan , Huang Haixiang , Chen Qian , Chen Guanyu , Zhu Wenjie , Chen Yuxi , Su Wenru , Chen Xiaoqing , Liang Dan 
Published: May 2022

AbstractBackgroundMelatonin, an indoleamine produced by the pineal gland, plays a pivotal role in maintaining circadian rhythm homeostasis. Recently, the strong antioxidant and anti-inflammatory properties of melatonin have attracted attention of researchers. We evaluated the therapeutic efficacy of melatonin in experimental autoimmune uveitis (EAU), which is a representative animal model of human autoimmune uveitis.MethodsEAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 1–20 (IRBP1–20). Melatonin was then administered via intraperitoneal injection to induce protection against EAU. With EAU induction for 14 days, clinical and histopathological scores were graded to evaluate the disease progression. T lymphocytes accumulation and the expression of inflammatory cytokines in the retinas were assessed via flow cytometry and RT-PCR, respectively. T helper 1 (Th1), T helper 17 (Th17), and regulatory T (Treg) cells were detected via flow cytometry for both in vivo and in vitro experiments. Reactive-oxygen species (ROS) from CD4 + T cells was tested via flow cytometry. The expression of thioredoxin-interacting protein (TXNIP) and hypoxia-inducible factor 1 alpha (HIF-1α) proteins were quantified via western blot.ResultsMelatonin treatment resulted in notable attenuation of ocular inflammation in EAU mice, evidenced by decreasing optic disc edema, few signs of retinal vasculitis, and minimal retinal and choroidal infiltrates. Mechanistic studies revealed that melatonin restricted the proliferation of peripheral Th1 and Th17 cells by suppressing their transcription factors and potentiated Treg cells. In vitro studies corroborated that melatonin restrained the polarization of retina-specific T cells towards Th17 and Th1 cells in addition to enhancing the proportion of Treg cells. Pretreatment of retina-specific T cells with melatonin failed to induce EAU in naïve recipients. Furthermore, the ROS/ TXNIP/ HIF-1α pathway was shown to mediate the therapeutic effect of melatonin in EAU.ConclusionsMelatonin regulates autoimmune T cells by restraining effector T cells and facilitating Treg generation, indicating that melatonin could be a hopeful treatment alternative for autoimmune uveitis.
Thrombin acts as inducer of proinflammatory macrophage migration inhibitory factor in astrocytes following rat spinal cord injury
Authors: Yang Ting , Jiang Haiyan , Luo Xinye , Hou Yuxuan , Li Aicheng , He Bingqiang , Zhang Xingyuan , Hao Huifei , Song Honghua , Cai Rixin , Wang Xudong , Wang Yingjie , Yao Chun , Qi Lei , Wang Yongjun 
Published: May 2022

Abstract
Background
The danger-associated molecular patterns (DAMPs) are critical contributors to the progressive neuropathology and thereafter affect the functional outcomes following spinal cord injury (SCI). Up to now, the regulatory mechanisms on their inducible production from the living cells remain elusive, aside from their passive release from the necrotic cells. Thrombin is immediately activated by the damaged or stressed central nervous system (CNS), which potently mediates inflammatory astrocytic responses through proteolytic cleavage of protease-activated receptors (PARs). Therefore, SCI-activated thrombin is conceived to induce the production of DAMPs from astrocytes at lesion site.

Methods
Rat SCI model was established by the cord contusion at T8–T10. The expression of thrombin and macrophage migration inhibitory factor (MIF) was determined by ELISA and Western blot. The PAR1, PAR3, and PAR4 receptors of thrombin were examined by PCR and immunohistochemistry. Primary astrocytes were isolated and purified from the spinal cord, followed by stimulation with different concentrations of thrombin either for transcriptome sequencing or for analysis of thrombin-mediated expression of MIF and related signal pathways in the presence or absence of various inhibitors. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale.

Results
MIF protein levels were significantly elevated in parallel with those of thrombin induced by SCI. Immunostaining demonstrated that PAR1 receptor, together with MIF, was abundantly expressed in astrocytes. By transcriptome sequencing and bioinformatical analysis of thrombin-stimulated primary astrocytes, MIF was identified to be dynamically regulated by the serine protease. Investigation of the underlying mechanism using various inhibitors revealed that thrombin-activated PAR1 was responsible for the MIF production of astrocytes through modulation of JNK/NFκB pathway. Administration of PAR1 inhibitor at lesion sites following SCI significantly reduced the protein levels of MIF and ameliorated functional deficits of rat locomotion.

Conclusion
SCI-activated thrombin is a robust inducer of MIF production from astrocytes. Exploring the roles of thrombin in promoting the production of DAMPs from astrocytes at lesion site will provide an alternative strategy for the clinical therapy of CNS inflammation.
Stability of enveloped and nonenveloped viruses in hydrolyzed gelatin liquid formulation
Authors: Kadji Francois Marie Ngako , Kotani Kazuki , Tsukamoto Hiroshi , Hiraoka Yosuke , Hagiwara Katsuro 
Published: May 2022

Abstract
Background
The thermal stability of viruses in gelatin liquid formulations for medical research and application is poorly understood and this study aimed to examine the thermal stability of 4 enveloped and nonenveloped DNA and RNA viruses in hydrolyzed gelatin liquid formulations.

Methods
Bovine herpesvirus (BHV) was used as a model virus to examine the molecular weight (MW), concentration and gelatin type and to optimize virus stability in liquid formulations at 25 °C and 4 °C. Using the model virus liquid formulation, the stability of multiple enveloped and nonenveloped RNA and DNA viruses, including parainfluenza virus, reovirus (RV), BHV, and adenovirus (AdV), was monitored over up to a 30-week storage period.

Results
The BHV model virus was considered stable after 3 weeks in hydrolyzed gelatin (MW: 4000) with a 0.8 LRV (log10 reduction value) at 25 °C or a 0.2 LRV at 4 °C, compared to the stabilities observed in higher MW gelatin (60,000 and 160,000) with an LRV above 1. Based on the gelatin type, BHV in alkaline-treated hydrolyzed gelatin samples were unexpectantly more stable than in acid-treated hydrolyzed gelatin sample. All four viruses exhibited stability at 4 °C for at least 8 weeks, BHV or AdV remained stable for over 30 weeks of storage, and at 25 °C, AdV and RV remained stable for 8 weeks.

Conclusion
The results demonstrated that 5% of 4000 MW hydrolyzed gelatin formulation can act as a relevant stabilizer for the thermal stability of viruses in medical research and application.
Breastfeeding, nutrition and type 1 diabetes: a case-control study in Izmir, Turkey
Authors: Çiçekli İpek , Durusoy Raika 
Published: May 2022

Abstract
Background
The relationship between infant breastfeeding and type 1 diabetes mellitus (DM) is unclear but it has been suggested that there may be a link between many environmental factors, including dietary antigens affecting diabetes epidemiology.
The main objective of this study is to investigate nutritional risk factors, especially breastfeeding early in life that may be associated with the development of type 1 DM and to determine the relationship these factors have with the disease.

Methods
This research is a case-control study and was carried out in Ege University Children’s Hospital in İzmir, Turkey between 13 January 2020 and 5 March 2020. A total of 246 children aged between 4 and 14 years were included in the study. The case group consisted of patients diagnosed with type 1 DM followed-up by Ege University Children’s Hospital’s Endocrinology Unit and the control group included non-diabetic children attending the same hospital’s General Pediatric Outpatient Clinic. A structured questionnaire was created by the researchers after reviewing the literature related to nutritional and other risk factors for type 1 DM. The questionnaire was administered by interviewing the parents and it was related to the child, mother and family of the child. In this study, breastfeeding duration was defined as the total duration of breastfeeding and exclusive breastfeeding meant that the child received only breast milk from the mother.

Results
The mean age at diagnosis was 6.30 ± 4.03 years for cases and 7.48 ± 2.56 years for controls. We found that each monthly increase in exclusive breastfeeding duration provided a 0.83-fold (95% CI 0.72, 0.96) decrease in the risk of type 1 DM. Introduction of cereals in the diet at the sixth month or earlier was associated with a 2.58-fold (95% CI 1.29, 5.16) increased risk.

Conclusions
Determining the contribution of exclusive breastfeeding to the disease is important in establishing preventive policies. A longer duration of exclusive breastfeeding may be an important role in preventing the disease. This free intervention that truly works will be cost-effective. Future studies are needed to clarify the role of both exclusive and non-exclusive breastfeeding on the development of type 1 DM.
Prevalence of iodine deficiency among Moroccan women of reproductive age
Authors: Rami Anass , Saeid Naima , El Mzibri Mohammed , El Kari Khalid , Idrissi Mohamed , Lahmam Houria , Mouzouni Fatima Zahra , Mounach Samir , El Ammari Laila , Benkirane Hasnae , Al Jawaldeh Ayoub , Zimmermann Micheal Bruce , Aguenaou Hassan 
Published: May 2022

Abstract
Background
Iodine deficiency disorders (IDD) affects nearly 1.9 million people worldwide. Iodine deficiency (ID) remains a public health concern not only for pregnant women, but for women of reproductive age (WRA) as well. This study was planned to evaluate the iodine status and the prevalence of iodine deficiency in a nationally representative sample of Moroccan WRA according to their socio-economic data and living areas.

Methods
This study is a cross-sectional national survey conducted on 1652 WRA aged between 18 and 49 years. Iodine status was assessed by the evaluation of the urinary iodine concentration (UIC) on spot urinary samples, using the Sandell-Kolthoff reaction, and by the estimation of iodine-rich food consumption, using a food frequency questionnaire. The World Health Organization cutoff of a median UIC of < 100 μg/l was used to define ID in the population.

Results
The median UIC [20th- 80th] was 71.3 μg/l [37.5–123.1] and 71% of participants had UIC < 100 μg/L, indicating insufficient iodine status and mild iodine deficiency. WRA from urban and rural areas showed an UIC median of 75.94 μg/l [41.16–129.97] and 63.40 μg/l [33.81–111.68], respectively. Furthermore, ID prevalence was significantly higher in rural areas (75.6%) as compared to urban areas (67.9%) (p < 0.05). Food frequency questionnaires analyses highlighted that dairy products are the most commonly consumed iodine-rich food, reported to be consumed daily by 43.1% of WRA. Of particular interest, 83.5% of WRA reported a weekly consumption of fish.

Conclusion
ID is still a public health problem in Morocco highlighting the necessity to implement effective national program, including efficient salt iodization, effective nutritional education and awareness, to control iodine deficiency and prevent IDD development.