bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teaching evolution in U.S. public schools: a continuing challenge
Authors: Plutzer Eric , Branch Glenn , Reid Ann 
Published: June 2020

AbstractBackgroundOver a decade ago, the first nationally representative probability survey concerning the teaching of evolution revealed disquieting facts about evolution education in the United States. This 2007 survey found that only about one in three public high school biology teachers presented evolution consistently with the recommendations of the nation’s leading scientific authorities. And about 13% of the teachers emphasized to their students that creationism was a valid scientific alternative to modern evolutionary biology. In this paper, we investigate how the quality of evolution teaching, as measured by teachers’ reports of their teaching practices with regard to evolution and creationism, has changed in the intervening 12 years.ResultsWe find substantial reductions in overtly creationist instruction and in the number of teachers who send mixed messages that legitimate creationism as a valid scientific alternative to evolutionary biology. We also report a substantial increase in the time that high school teachers devote to human evolution and general evolutionary processes. We show that these changes reflect both generational replacement—from teachers who are new to the profession—and changes in teaching practices among those who were teaching in the pre-Kitzmillerera.ConclusionAdoption of the Next Generation Science Standards, along with improvements in pre-service teacher education and in-service teacher professional development, appears to have contributed to a large reduction in both creationist instruction and mixed messages that could lead students to think that creationism is a scientific perspective. Combined with teachers devoting more hours to evolution—including human evolution—instruction at the high school level has improved by these measures since the last national survey in 2007.
Tolfenamic acid inhibits GSK-3β and PP2A mediated tau hyperphosphorylation in Alzheimer’s disease models
Authors: Zhang Huiming , Wang Xiaojuan , Xu Pu , Ji Xuefei , Chi Tianyan , Liu Peng , Zou Libo 
Published: June 2020

AbstractTolfenamic acid, a nonsteroidal anti-inflammatory drug, alleviated learning and memory deficits and decreased the expression of specificity protein 1 (SP1)-mediated cyclin-dependent kinase-5 (CDK5), a major protein kinase that regulates hyperphosphorylated tau, in Alzheimer’s disease (AD) transgenic mice. However, whether tolfenamic acid can regulate the major tau protein kinase, glycogen synthase kinase-3β (GSK-3β), or tau protein phosphatase, protein phosphatase 2A (PP2A), further inhibiting hyperphosphorylation of tau, remains unknown. To this end, tolfenamic acid was administered i.p. in a GSK-3β overactivation postnatal rat model and orally in mice after intracerebroventricular (ICV) injection of okadaic acid (OA) to develop a PP2A inhibition model. We used four behavioural experiments to evaluate memory function in ICV-OA mice. In this study, tolfenamic acid attenuated memory dysfunction. Tolfenamic acid decreased the expression of hyperphosphorylated tau in the brain by inhibiting GSK-3β activity, decreasing phosphorylated PP2A (Tyr307), and enhancing PP2A activity. Tolfenamic acid also increased wortmannin (WT) and GF-109203X (GFX) induced phosphorylation of GSK-3β (Ser9) and prevented OA-induced downregulation of PP2A activity in PC12 cells. Altogether, these results show that tolfenamic acid not only decreased SP1/CDK5-mediated tau phosphorylation, but also inhibited GSK-3β and PP2A-mediated tau hyperphosphorylation in AD models.
Substance P enhances the local activation of NK1R-expressing c-kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart
Authors: Jeong Yun-Mi , Cheng Xian Wu , Lee Kyung Hye , Lee Sora , Cho Haneul , Kim Weon 
Published: June 2020

Abstract
Background
Localization of neurokinin 1 receptor (NK1R), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NK1R signal pathways in the RA remains unclear.
Sprague-Dawley rats were randomly divided into 4 groups (n = 22 each); subjected to sham, ischemia/reperfusion-injury (I/R), I/R with 5 nmole/kg SP injection (SP + I/R), and SP + I/R with 1 mg/kg RP67580 injection (RP, a selective non-peptide tachykinin NK1R antagonist) (RP/SP + I/R). The left anterior descending coronary artery was occluded for 40 min followed by 1 day reperfusion with SP or SP + RP or without either. After 1 day, both atria and ventricles as well as the heart apexes were collected.

Results
SP promoted the expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 in only the RA of the SP + I/R rats via NK1R activation. In agreement with these observations, NK1R-expressing c-Kit+ Nkx2.5+GATA4+ cardiac progenitor cells (CPCs) in the ex vivo RA explant outgrowth assay markedly migrated out from RA1 day SP + I/R approximately 2-fold increase more than RA1 day I/R. Treatment of SP promoted proliferation, migration, cardiosphere formation, and potential to differentiate into cardiomyocytes. Using RP inhibitor, NK1R antagonist not only inhibited cell proliferation and migration but also reduced the formation of cardiosphere and differentiation of c-Kit+ CPCs.

Conclusion
SP/NK1R might play a role as a key mediator involved in the cellular response to c-Kit+ CPC expansion in RA of the heart within 24 h after I/R.
Core competencies for health headquarters: a systematic review and meta-synthesis
Authors: Fattahi Hamed , Abolghasem Gorji Hasan , Bayat Mahboubeh 
Published: June 2020

Abstract
Background
The availability of human resources for the health sector is not enough requirement for addressing health needs. Instead, it is necessary to take effective steps to meet the requirements of the health care system in case the system has the necessary competencies. This study was performed to identify the competencies of health headquarters in meeting the needs of the health system.

Methods
This thematic synthesis was performed to develop a set of central themes that summarize all the topics raised in the articles reviewed in this study. The quality of the articles was assessed by the Standards for Reporting Qualitative Research.

Results
We included 12 articles from seven countries. Seven central themes were inductively developed from the analysis: (1) Leadership and management, (2) Analyzing, interpreting, and reporting, (3) Public health knowledge, (4) Interpersonal relationship, (5) Personality competencies, (6) Cultural and community competencies, and (7) International/Global health competencies.

Conclusion
The findings of this review may help to address how to recruit and retain health headquarters, optimize the headquarters ability and expertise, and develop some approaches to promote their scientific, practical, and professional levels. These issues can drive the organization toward their visions, strategies, and great objectives.
Giant recurrent left inguinal hernia with femoral nerve injury: a report of a rare case
Authors: Lin Manzhou , Long Guojie , Chen Ming , Chen Weice , Mo Jian , Chen Nianping 
Published: June 2020

Abstract
Background
Giant inguinal hernia(GIH), a rare disease, has brought great challenges to surgeons. GIH is defined as an inguinal hernia that extends below the midpoint of the inner thigh in standing position. However, a giant recurrent inguinal hernia resulting from previous operations that destroy the anatomical structure of the inguinal region is extremely rare. Nerve injury, a complication following inguinal hernia repair, is mostly found in ilioinguinal nerve and iliohypogastric nerve, which often presents as numbness and acute or chronic pain, while postoperative muscular dysfunction results from femoral nerve injury is rare.

Case presentation
A 77-years-old woman presented with a complaint of a reducible mass in the left inguinal of duration 1 year. The patient had three previous inguinal hernia repairs. Physical examination and auxiliary examination indicated a giant inguinal hernia with femoral nerve injury. After preoperative evaluation and preparation, a transabdominal partial extraperitoneal(TAPE) repair have performed. Finally, the patient recovered and was discharged.

Conclusions
In conclusion, we reported a rare case of a giant recurrent inguinal hernia with femoral nerve injury and made a successful treatment for the patient via transabdominal partial extraperitoneal(TAPE) repair.
Duration of immunity against heterologous porcine parvovirus 1 challenge in gilts immunized with a novel subunit vaccine based on the viral protein 2
Authors: Garcia-Morante Beatriz , Noguera Marta , Klocke Sonja , Sommer Kathrin , Bridger Philip 
Published: June 2020

Abstract
Background
Porcine parvovirus 1 (PPV1) is widespread in commercial pig farms worldwide and has a significant impact to the swine industry. Long-lasting immunity achieved by means of vaccination is the main tool to prevent PPV1 infection and its associated clinical signs. Here we evaluated the duration of immunity (DOI) conferred by a novel subunit vaccine based on the viral protein (VP) 2 of PPV1, named ReproCyc® ParvoFLEX. The DOI was assessed at 6 months post-vaccination following the standard vaccination scheme (phase I) or after re-vaccination (phase II) with a single injection administered 24 weeks after the basic vaccination scheme. A total of 46, five to six-month-old gilts, free of PPV1 and porcine reproductive and respiratory syndrome virus (PRRSV), were randomly assigned to 6 groups (three in each phase): the negative control groups were inoculated with sodium chloride (NaCl), the vaccinated groups were immunized with the PPV1 subunit vaccine and the strict controls were neither treated nor challenged. Subsequently, the negative control and vaccinated groups from each phase were challenged with a heterologous PPV1 strain. Infection of fetuses was the primary outcome parameter for efficacy, though other supportive parameters were PPV1 viremia and serological status of the gilts and the condition of their fetuses (i.e. normal, autolytic, or mummified).

Results
All gilts vaccinated against PPV1 tested seropositive at challenge and viremia after challenge was detectable only in the non-vaccinated animals. In this regard, fetuses positive to PPV1 by PCR were only found in litters from non-vaccinated sows.

Conclusions
These results point out that the immunity developed by the PPV1 subunit vaccine is effective in terms of preventing viremia, transplacental infection of fetuses and fetal death caused by PPV1 infection. ReproCyc® ParvoFLEX was demonstrated to protect fetuses against heterologous PPV1 challenge with a DOI of 6 months after vaccination.
Compared to plasma, bronchial washing fluid shows higher diagnostic yields for detecting EGFR-TKI sensitizing mutations by ddPCR in lung cancer
Authors: Lee Sang Hoon , Kim Eun Young , Kim Taehee , Chang Yoon Soo 
Published: June 2020

Abstract
Background
The rate of diagnosis of advanced lung adenocarcinoma must be improved. In this study, we compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference.

Methods
Paired blood and BWF specimens were collected from 73 patients with lung cancer. The tumor EGFR mutation status was determined by genotyping of the plasma and BWF samples using droplet digital PCR (ddPCR).

Results
The study cohort included 26, 10, 10, and 27 patients with stage I, II, III, and IV disease. Of the 73 cases, 35 had a wild-type EGFR, and 19 had the L858R substitution and exon 19 deletion mutations. The areas under the receiver operator characteristic curves for sensitivity vs. specificity of ddPCR were 0.895 [95% confidence interval (CI): 0.822–0.969] for BWF and 0.686 (95% CI: 0.592–0.780) for plasma (p < 0.001). The fractional abundance was higher in BWF of the mEGFR-positive cases than in the plasma (p = 0.004), facilitating easy threshold setting and discrimination between mEGFR-positive and negative cases. When genotyping results obtained using plasma and BWF were compared for early lung cancer (stages I–IIIA), the diagnostic yields were significantly higher for BWF ddPCR, and the same tendency was observed for the advanced stages, suggesting that the BWF data may reflect the genotype status in early-stage patients.

Conclusions
The mEGFR genotyping results obtained using BWF showed a higher diagnostic efficacy than did those obtained using the plasma. Thus, BWF-based genotyping may be a useful substitute for that using plasma in lung cancer.
A critical review to grading systems and recommendations of traditional Chinese medicine guidelines
Authors: Li Juan , Li Bin , Zhao Xin-ke , Tu Jia-yin , Li Yingdong 
Published: June 2020

Abstract
Objectives
To investigate how many traditional Chinese medicine (TCM) guidelines adopted a grading system and the differences among them, and the distribution of level of evidence used to support TCM recommendations.

Methods
A comprehensive search of relevant guideline webpages and literature databases were undertaken from inception to August 2018 to identify guidelines including TCM interventions. Two independent reviewers extracted the information about grading systems and recommendations.

Results
One hundred forty-two TCM guidelines were included, among which, 68 (47.9%) adopted a total of eight grading systems. The definitions, letters, and codes among these systems varied significantly. A total of 1284 recommendations were extracted from included TCM guidelines. More than 60% recommendations were based on a low and very low level of evidence (level C:33.4% and level D: 30.2%). Only 7.8% recommendations were rated as strong recommendation (grade I), while 76.2% recommendations were rated as conditional recommendation (grade II).

Conclusions
Various grading systems were used in TCM guidelines, which might confuse guideline users. The low proportion of high level of evidence in TCM recommendations might downgrade the confidence to TCM interventions.
Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells
Authors: Kim Yukeyoung , Ghil Sungho 
Published: June 2020

Abstract
Background
Protease-activated receptor 4 (PAR4) is a seven transmembrane G-protein coupled receptor (GPCR) activated by endogenous proteases, such as thrombin. PAR4 is involved in various pathophysiologies including cancer, inflammation, pain, and thrombosis. Although regulators of G-protein signaling (RGS) are known to modulate GPCR/Gα-mediated pathways, their specific effects on PAR4 are not fully understood at present. We previously reported that RGS proteins attenuate PAR1- and PAR2-mediated signaling through interactions with these receptors in conjunction with distinct Gα subunits.

Methods
We employed a bioluminescence resonance energy transfer technique and confocal microscopy to examine potential interactions among PAR4, RGS, and Gα subunits. The inhibitory effects of RGS proteins on PAR4-mediated downstream signaling and cancer progression were additionally investigated by using several assays including ERK phosphorylation, calcium mobilization, RhoA activity, cancer cell proliferation, and related gene expression.

Results
In live cells, RGS2 interacts with PAR4 in the presence of Gαq while RGS4 binding to PAR4 occurs in the presence of Gαq and Gα12/13. Co-expression of PAR4 and Gαq induced a shift in the subcellular localization of RGS2 and RGS4 from the cytoplasm to plasma membrane. Combined PAR4 and Gα12/13 expression additionally promoted translocation of RGS4 from the cytoplasm to the membrane. Both RGS2 and RGS4 abolished PAR4-activated ERK phosphorylation, calcium mobilization and RhoA activity, as well as PAR4-mediated colon cancer cell proliferation and related gene expression.

Conclusions
RGS2 and RGS4 forms ternary complex with PAR4 in Gα-dependent manner and inhibits its downstream signaling. Our findings support a novel physiological function of RGS2 and RGS4 as inhibitors of PAR4-mediated signaling through selective PAR4/RGS/Gα coupling.
Remodelling of the bone marrow microenvironment by stromal hyaluronan modulates the malignancy of breast cancer cells
Authors: Chen Xiaoyan , Shi Xiaoxing , Liu Yiwen , He Yiqing , Du Yan , Zhang Guoliang , Yang Cuixia , Gao Feng 
Published: June 2020

Abstract
Background
Hyaluronan (HA) is an abundant component of the bone marrow (BM) extracellular matrix. Here, we investigated the abnormal deposition of HA in the BM microenvironment and its remodelling in mediating the malignancy of breast cancer cells (BCCs).

Methods
BCCs were transplanted into nude mice by intracardiac injection. The BCCs were cocultured with BM-derived stromal HS5 cells. Then, the abnormal metabolism of HA and its correlation with the malignant growth and the intracellular signalling pathways of the BCCs were investigated. After knockdown/out of the HA receptor CD44 in cancer cells by shRNA and CRISPR/Cas9, the mechanism was investigated in vivo through intratibial inoculation and in vitro by coculture with HS5 cells.

Results
The malignancy of cancer cells was highly related to the degree of accumulation of HA in the BM. Further, stromal cell-derived HA, especially the mixed complex, significantly promoted the growth of BCCs and osteolysis by binding to the CD44 receptor. Additionally, the investigation of the underlying mechanism revealed that the PI3K, Cyclin D1, and CDK4 pathways were involved in the effect of bone stromal cell-derived HA on the BCC activities.

Conclusion
These data suggested that HA in abnormal BM stroma might be a therapeutic candidate for bone metastasis of breast cancer.

Graphical abstract
Extracellular vesicles in diabetes mellitus induce alterations in endothelial cell morphology and migration
Authors: Wu Sharon F. , Noren Hooten Nicole , Freeman David W. , Mode Nicolle A. , Zonderman Alan B. , Evans Michele K. 
Published: June 2020

AbstractBackgroundInflammation-related atherosclerotic peripheral vascular disease is a major end organ complication of diabetes mellitus that results in devastating morbidity and mortality. Extracellular vesicles (EVs) are nano-sized particles that contain molecular cargo and circulate in the blood. Here, we examined EV protein cargo from diabetic individuals and whether these EVs cause functional changes in endothelial cells.MethodsWe quantified inflammatory protein levels in plasma-derived EVs from a longitudinal cohort of euglycemic and diabetic individuals and used in vitro endothelial cell biological assays to assess the functional effects of these EVs with samples from a cross-sectional cohort.ResultsWe found several significant associations between EV inflammatory protein levels and diabetes status. The angiogenic factor, vascular endothelial growth factor A (VEGF-A), was associated with diabetes status in our longitudinal cohort. Those with diabetes mellitus had higher EV VEGF-A levels compared to euglycemic individuals. Additionally, EV levels of VEGF-A were significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B). To test whether EVs with different inflammatory cargo can demonstrate different effects on endothelial cells, we performed cell migration and immunofluorescence assays. We observed that EVs from diabetic individuals increased cell lamellipodia formation and migration when compared to EVs from euglycemic individuals.ConclusionsHigher levels of inflammatory proteins were found in EVs from diabetic individuals. Our data implicate EVs as playing important roles in peripheral vascular disease that occur in individuals with diabetes mellitus and suggest that EVs may serve as an informative diagnostic tool for the disease.
Collapsing the list of myocardial infarction-related differentially expressed genes into a diagnostic signature
Authors: Osmak German , Baulina Natalia , Koshkin Philipp , Favorova Olga 
Published: June 2020

Abstract
Background
Myocardial infarction (MI) is one of the most severe manifestations of coronary artery disease (CAD) and the leading cause of death from non-infectious diseases worldwide. It is known that the central component of CAD pathogenesis is a chronic vascular inflammation. However, the mechanisms underlying the changes that occur in T, B and NK lymphocytes, monocytes and other immune cells during CAD and MI are still poorly understood. One of those pathogenic mechanisms might be the dysregulation of intracellular signaling pathways in the immune cells.

Methods
In the present study we performed a transcriptome profiling in peripheral blood mononuclear cells of MI patients and controls. The machine learning algorithm was then used to search for MI-associated signatures, that could reflect the dysregulation of intracellular signaling pathways.

Results
The genes ADAP2, KLRC1, MIR21, PDGFD and CD14 were identified as the most important signatures for the classification model with L1-norm penalty function. The classifier output quality was equal to 0.911 by Receiver Operating Characteristic metric on test data. These results were validated on two independent open GEO datasets. Identified MI-associated signatures can be further assisted in MI diagnosis and/or prognosis.

Conclusions
Thus, our study presents a pipeline for collapsing the list of differential expressed genes, identified by high-throughput techniques, in order to define disease-associated diagnostic signatures.
High-salt diet decreases mechanical thresholds in mice that is mediated by a CCR2-dependent mechanism
Authors: Fan Anni , Oladiran Oladayo , Shi Xiang Qun , Zhang Ji 
Published: June 2020

Abstract
Background
Though it is well-known that a high-salt diet (HSD) is associated with many chronic diseases, the effects of long-term high-salt intake on physiological functions and homeostasis remain elusive. In this study, we investigated whether and how an HSD affects mouse nociceptive thresholds, and myeloid cell trafficking and activation.

Methods
Healthy C57BL/6 male and female mice were fed an HSD (containing 4% NaCl in chow and 1% NaCl in water) from the time of weaning for 3 to 4 months. Circulating monocytes, nerve macrophages, spinal microglia, and associated inflammatory responses were scrutinized using flow cytometry, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR) approaches. Mouse pain sensitivity to mechanical stimuli was monitored with von Frey tests along the experimental duration.

Results
Mice on an HSD have reduced mechanical thresholds. They feel more pain than those on a normal diet (ND), e.g., regular laboratory chow (0.3% NaCl in chow). An HSD induced not only a remarkable expansion of circulating monocytes, CCR2+Ly6Chi inflammatory monocytes in particular, but also an accumulation of CD11b+F4/80+ macrophages in the peripheral nerves and an activation of Iba-1+ spinal microglia. Replacing an HSD with a ND was unable to reverse the HSD-induced mechanical hypersensitivity or rescue the altered immune responses. However, treating HSD-fed mice with a chemokine receptor CCR2 antagonist effectively normalized the pain thresholds and immune cell profile in the periphery and spinal cord. An HSD failed to alter pain thresholds and myeloid cell activation in CCR2-deficient mice. Spinal microglial activation is required for HSD-induced mechanical hypersensitivity in male, but not in female mice.

Conclusion
Overall, this study provides evidence that an HSD has a long-term impact on physiological function. CCR2-mediated cellular response, including myeloid cell trafficking and associated inflammation, plays pivotal roles in salt-dietary modulation of pain sensitivity.