bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative transcriptome analysis suggests convergent evolution of desiccation tolerance in Selaginella species
Authors: Alejo-Jacuinde Gerardo , González-Morales Sandra Isabel , Oropeza-Aburto Araceli , Simpson June , Herrera-Estrella Luis
Published: October 2020

Background

Desiccation tolerant Selaginella species evolved to survive extreme environmental conditions. Studies to determine the mechanisms involved in the acquisition of desiccation tolerance (DT) have focused on only a few Selaginella species. Due to the large diversity in morphology and the wide range of responses to desiccation within the genus, the understanding of the molecular basis of DT in Selaginella species is still limited.

Results

Here we present a reference transcriptome for the desiccation tolerant species S. sellowii and the desiccation sensitive species S. denticulata. The analysis also included transcriptome data for the well-studied S. lepidophylla (desiccation tolerant), in order to identify DT mechanisms that are independent of morphological adaptations. We used a comparative approach to discriminate between DT responses and the common water loss response in Selaginella species. Predicted proteomes show strong homology, but most of the desiccation responsive genes differ between species. Despite such differences, functional analysis revealed that tolerant species with different morphologies employ similar mechanisms to survive desiccation. Significant functions involved in DT and shared by both tolerant species included induction of antioxidant systems, amino acid and secondary metabolism, whereas species-specific responses included cell wall modification and carbohydrate metabolism.

Conclusions

Reference transcriptomes generated in this work represent a valuable resource to study Selaginella biology and plant evolution in relation to DT. Our results provide evidence of convergent evolution of S. sellowii and S. lepidophylla due to the different gene sets that underwent selection to acquire DT
Massive iron overload and acute-on-chronic liver failure in a patient with Diamond–Blackfan anaemia: a case report
Authors: Assis-Mendonça Guilherme Rossi , Cunha-Silva Marlone , Fernandes Mariana Franson , Torres Luiza Dias , de Almeida Verissimo Monica Pinheiro , Okano Marcelo Trevisan Neves , Mazo Daniel Ferraz , Lalli Cristina Alba , Sevá-Pereira Tiago , Stelini Rafael Fantelli , da Costa Larissa Bastos Eloy
Published: October 2020

Background

Genetic anaemias lead us to reflect on the classic ‘trolley dilemma’, when there are two choices but neither one is satisfactory. Either we do not treat anaemia and the patient suffers from chronic tiredness and fatigue, or we do treat it through blood transfusions, leading to iron overload, which is a quite harmful consequence.

Case presentation

We present the case of a 34-year-old woman with Diamond–Blackfan anaemia (DBA). Bone marrow stem cell transplantation had not been accessible during her childhood, so she had been submitted to monthly blood transfusions throughout her life, leading to a hepatitis C virus infection (which was treated, achieving a sustained virological response when she was 18 years old), and secondary haemochromatosis. Despite chelation therapy, diffuse iron deposition was occurring in multiple organs, markedly in the heart and liver. Her serum ferritin was higher than 21,000 ng/mL and transferrin saturation reached 102%. When she faced heart decompensation, this congestive condition led to an acute liver injury overlapping pre-existing hepatic fibrosis. She progressed to haemodynamic and hepatic failure, with clinical features of acute-on-chronic liver failure (ACLF). Despite therapeutic optimisation, she died of respiratory insufficiency. An autopsy was performed and revealed the macroscopic and microscopic findings of a massive iron deposition in the liver, heart, lungs, spleen, bone marrow, thyroid and adrenal glands. We found marked advance of liver fibrosis (chronic damage), as well as necrosis of hepatocytes in zone 3 of the Rappaport acinus (acute damage), supporting the hypothesis of ACLF. The main feature responsible for acute liver decompensation seemed to be heart insufficiency.

Conclusion

This is the first case reporting the sequence: DBA, multiple blood transfusions, secondary haemochromatosis, advanced liver fibrosis, heart failure, ACLF and death. A multidisciplinary team is essential to care for DBA patients, since there is a significant emotional burden related to the disease, which might impair an effective chelation therapy and lead to severe consequences due to iron deposition.
KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas
Authors: Catic Aida , Kurtovic-Kozaric Amina , Sophian Ardis , Mazur Lech , Skenderi Faruk , Hes Ondrej , Rohan Stephen , Rakheja Dinesh , Kogan Jillene , Pins Michael R.
Published: October 2020

Background

Metanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell carcinoma in adults and Wilms̕ tumor in children. Despite recent advancements in tumor genomics, there is limited data available regarding the genetic alterations characteristic of MA. The purpose of this study is to determine the frequency of metanephric adenoma cases exhibiting cytogenetic aberration t (9;15)(p24;q24), and to investigate the association between t (9,15) and BRAF mutation in metanephric adenoma.

Methods

This study was conducted on 28 archival formalin fixed paraffin-embedded (FFPE) specimens from patients with pathologically confirmed MA. Tissue blocks were selected for BRAF sequencing and fluorescent in situ hybridization (FISH) analysis for chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3), which was previously characterized and described in two MA cases.

Results

BRAFV600E mutation was identified in 62% of our cases, 9 (38%) cases were BRAFWT, and 4 cases were uninformative. Of the 20 tumors with FISH results, two (10%) were positive for KANK1-NTRK3 fusion. Both cases were BRAFWT suggesting mutual exclusivity of BRAFV600E and KANK1-NTRK3 fusion, the first such observation in the literature.

Conclusions

Our data shows that BRAF mutation in MA may not be as frequent as suggested in the literature and KANK-NTRK3 fusions may account for a subset of BRAFWT cases in younger patients. FISH analysis for KANK1-NTRK3 fusion or conventional cytogenetic analysis may be warranted to establish the diagnosis of MA in morphologically and immunohistochemically ambiguous MA cases lacking BRAF mutations.
Recognition of stroke-related knowledge among community residents and the improvement after intensive health education: a cross-sectional study
Authors: Zhong Xuemin , Wang Jian , He Lanying , Xu Ronghua
Published: October 2020

Background

The high morbidity, mortality, and disability rates of stroke constitute a heavy burden to the society. The level of understanding about stroke warning symptoms and first aid systems among community residents was generally low. The aim of our work is to investigate stroke-related knowledge in community residents of Jinjiang district of Chengdu and to raise public awareness about stroke through an intensive educational program.

Methods

Nine communities in Jinjiang district were sampled and a questionnaire about stroke-related knowledge was applied before and after stroke educational activities. We analyzed the impact of such activities in stroke recognition and management.

Results

We collected 1685 valid questionnaires. The awareness about stroke risk before educational activities was 11.4%. The recognition of stroke warning signs among community residents was 29.8–59.5%. Among them, the recognition of major signs, such as limb weakness, language disorder, and imbalance was more than 50%. When faced with five stroke warning signs, the proportion of participants who chose to make an emergency call was 41.5%. Less than 10% of the participants chose to consult a doctor, take medicine, or wait. After strengthening publicity and educational activities regarding stroke, there was a significant improvement in the identification of stroke risk factors, warning signs, and stroke management. The percentage of participants who chose to make an emergency call increased from 53.2 to 82.7%.

Conclusions

The knowledge about stroke among community residents in Jinjiang District of Chengdu was low. Strengthening publicity and educational activities may raise awareness about stroke prioritizing call emergency after the onset of stroke signs.
Burden, associated risk factors and adverse outcomes of gestational diabetes mellitus in twin pregnancies in Al Ain, UAE
Authors: Alkaabi Juma , Almazrouei Raya , Zoubeidi Taoufik , Alkaabi Fatema M. , Alkendi Fatima Rashid , Almiri Amel Eisa , Sharma Charu , Souid Abdul-Kader , Ali Nasloon , Ahmed Luai A.
Published: October 2020

Background

Gestational diabetes mellitus (GDM) in singleton pregnancies represent a high-risk scenario. The incidence, associated factors and outcomes of GDM in twin pregnancies is not known in the UAE.

Methods

This was five years retrospective analysis of hospital records of twin pregnancies in the city of Al Ain, Abu Dhabi, UAE. Relevant data with regards to the pregnancy, maternal and birth outcomes and incidence of GDM was extracted from two major hospitals in the city. Regression models assessed the relationship between socio-demographic and pregnancy-related variables and GDM, and the associations between GDM and maternal and fetal outcomes at birth.

Results

A total of 404 women and their neonates were part of this study. The study population had a mean age of 30.1 (SD: 5.3), overweight or obese (66.5%) and were majority multiparous (66.6%). High incidence of GDM in twin pregnancies (27.0%). While there were no statistical differences in outcomes of the neonates, GDM mothers were older (OR: 1.09, 95% CI: 1.06–1.4) and heavier (aOR: 1.02, 95% CI: 1.00 -1.04). They were also likely to have had GDM in their previous pregnancies (aOR: 7.37, 95% CI: 2.76–19.73). The prognosis of mothers with twin pregnancies and GDM lead to an independent and increased odds of cesarean section (aOR: 2.34, 95% CI: 1.03–5.30) and hospitalization during pregnancy (aOR: 1.60, 95% CI: 1.16–2.20).

Conclusion

More than a quarter of women with twin pregnancies were diagnosed with GDM. GDM was associated with some adverse pregnancy outcomes but not fetal outcomes in this population. More studies are needed to further investigate these associations and the management of GDM in twin pregnancies.
Unexpectedly high prevalence of asthenopia in Australian school children identified by the CISS survey tool
Authors: Junghans Barbara M. , Azizoglu Serap , Crewther Sheila G.
Published: October 2020

Background

To date there have been few systematic attempts to establish the general prevalence of asthenopia in unselected populations of school-aged children. Thus, the aim of this study was to determine whether the incorporation of Borsting et al’s 2003 Revised Convergence-Insufficiency Symptom Survey (CISS) into a general school vision screening could aid in the identification of children with visual discomfort and indicate the need for further investigation.

Methods

Vision screening of an unselected middle school population investigated and analysed the incidence of self-reported nearwork-related visual discomfort via the CISS along with distance and near visual acuities plus non-cycloplegic autorefraction using a Shin-Nippon NVision-K 5001.

Results

Of the 384 unselected students approached in Grades 6–9, 353 participated (92.2%, mean 13.2 ± 1.4 years). The mean CISS score for the population without amblyopia and/or strabismus (96.0% of all students) was 16.8 ± 0.6, i.e., 45% of students in this cohort had CISS scores greater than one standard deviation above the mean found by Borsting et al. in 2003 during their validation study of the CISS on 9 to 18 year old children without binocular anomalies. Regression analyses indicated significantly higher (p < 0.001) mean CISS scores for the 3.2% who were hyperopes ≥ + 2.00D by non-cycloplegic autorefraction (27.7 ± 14.7) and for those who were amblyopic (24.3 ± 6.6) or strabismic (34.0 ± 9.8). The mean CISS score of 31.6 ± 9.0 for non-amblyopic/strabismic students having near vision poorer than 0.1 LogMAR was significantly higher (p < 0.001) than for those with good acuity.

Conclusion

The most important finding of this study was the high incidence of asthenopia in an unselected population and that refractive status per se was not a major contributor to CISS scores. The results highlight the usefulness of the CISS questionnaire for assessment of visual discomfort in school vision screenings and the need for future exploration of near binocular vision status as a potential driver of asthenopia in school students, especially given current trends for frequent daily use of computers and handheld devices and necessarily prolonged accommodative-convergence effort at near, both at school and at home.
Distinct effects of over-general autobiographical memory on suicidal ideation among depressed and healthy people
Authors: Jiang Wen , Hu Guangtao , Zhang Jingxuan , Chen Ken , Fan Dongni , Feng Zhengzhi
Published: October 2020

Background

Childhood trauma and over-general autobiographical memory (OGM) are crucial risk factors of suicide. This study aimed to investigate whether suicidal ideation was predicted by one’s childhood trauma and OGM and the mechanism of OGM underlying suicidal ideation in depression patients and healthy controls.

Methods

A total of 180 depression patients and 176 matched healthy individuals were recruited in this study. Data were analyzed using descriptive statistics, and Pearson’s correlation coefficient was obtained. Path analysis was conducted to test a meditational model. The multigroup comparison was applied to find differences between groups.

Results

Significant differences were detected between depression patients and healthy controls with respect to childhood trauma, OGM, suicidal ideation, and suicidal behavior. OGM was positively correlated with both current and worst-point suicidal ideation in the depression group and significantly correlated with worst-point suicidal ideation in the healthy control group. The path model showed that childhood trauma had a direct impact on the current suicidal ideation directly, and an indirect influence through OGM and worst-point suicidal ideation. Multigroup analysis further demonstrated that OGM affected and mediated the current suicidal ideation due to childhood trauma in depression patients, whereas only worst-point suicidal ideation was affected in healthy controls.

Conclusions

The OGM mediates suicidal ideation in depression patients, but only affects the worst-point suicidal ideation in the healthy controls. As it is one of the major risk factors of suicidal ideation in depression, amelioration of OGM might be an useful method to reduce or prevent suicidal ideation in depression patients.
ADHD subtype-specific cognitive correlates and association with self-esteem: a quantitative difference
Authors: Molavi Parviz , Nadermohammadi Mehriar , Salvat Ghojehbeiglou Habibeh , Vicario Carmelo M. , Nitsche Michael A. , Salehinejad Mohammad Ali
Published: October 2020

Background

Attention-deficit hyperactivity disorder (ADHD) is a major neurodevelopmental disorder with heterogeneous symptoms, subtypes, and cognitive deficits. Cognitive deficits are central to ADHD pathophysiology and one potential source of heterogeneity in ADHD. Subtype-specific cognitive correlates are not, however, well-studied. We explored cognitive correlates of ADHD subtypes based on the Wechsler Intelligence Scale for Children (WISC-IV) scores. We also assessed subtype-specific self-esteem rating in ADHD subtypes and explored its association with cognitive correlates.

Methods

One hundred thirty-nine children with ADHD (80.6% boy, 19.4% girl) were categorized into the predominantly “hyperactive (ADHD-H)”, “inattentive (ADHD-I)” and “combined (ADHD-C)” subtype based on their symptoms and scores on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL) and Conners Parent-Rating Scale (CPRS-RS). They were then individually administrated the WISC-IV and completed a self-esteem inventory. Group differences in the WISC-IV indices and their predictability in discriminating ADHD subtypes were analyzed.

Results

We found a quantitative differentiation of cognitive abilities among ADHD subtypes with “working memory” as the most compromised cognitive domain. ADHD-I had the poorest cognitive profile while ADHD-H scored highest in all cognitive domains. Importantly, cognitive abilities were negatively correlated with inattention and positively correlated with hyperactive symptoms. Moreover, self-esteem ratings were positively correlated with the cognitive domains and were rated differently based on the subtypes. ADHD-H, with the highest cognitive strength, reported the highest level of self-esteem among all subtypes.

Conclusions

ADHD subtype-specific symptoms, cognitive deficits, and self-esteem problems should be considered for precise diagnosis and effective and personalized treatment in ADHD in light of further supporting evidence and assessments. Cognitive interventions might be more compatible with and effective in inattentive and combined subtypes of ADHD. Working memory improving-based interventions can benefit all ADHD subtypes. A supportive educational system in school and providing adjunct supportive interventions should be considered for children with ADHD as well.
Pretreatment with atorvastatin ameliorates cobra venom factor-induced acute lung inflammation in mice
Authors: Guo Jing , Li Min , Yang Yi , Zhang Lin , Zhang Li-wei , Sun Qian-yun
Published: October 2020

Background

The complement system plays a critical role as the pathogenic factor in the models of acute lung injury due to various causes. Cobra venom factor (CVF) is a commonly used complement research tool. The CVF can cause acute inflammation in the lung by producing complement activation components. Atorvastatin (ATR) is a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor approved for control of plasma cholesterol levels. This inhibitor can reduce the acute pulmonary inflammatory response. However, the ability of ATR in treating acute lung inflammation caused by complement activation is still unknown. Therefore, we investigated the effect of ATR on lung inflammation in mice induced by activation of the complement alternative pathway in this study.

Methods

ATR (10 mg/kg/day via oral gavage) was administered for 7 days before tail vein injection of CVF (25 μg/kg). On the seventh day, all mice were sacrificed 1 h after injection. The lung lobe, bronchoalveolar lavage fluid (BALF), and blood samples were collected. The myeloperoxidase (MPO) activity of the lung homogenate, the leukocyte cell count, and the protein content of BALF were measured. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), P-selectin, and Intercellular cell adhesion molecule-1 (ICAM-1) in BALF and serum were determined by enzyme-linked immunosorbent assay. The pathological change of the lung tissue was observed by hematoxylin and eosin staining. The deposition of C5b-9 in the lung tissue was detected by immunohistochemistry. The phosphorylation of NF-κB p65 in the lung tissues was examined by immunohistochemistry and western blotting.

Results

The lung inflammation levels were determined by measuring the leukocyte cell numbers and protein content of BALF, the lung MPO activity, and expression and staining of the inflammatory mediators (IL-6 and TNF-α), and adhesion molecules (P-selectin and ICAM-1) for lung lesion. A significant reduction in the lung inflammation levels was observed after 7 days in ATR pre-treated mice with a CVF-induced lung disease. Deposition of C5b-9 was significantly alleviated by ATR pretreatment. Early intervention with ATR significantly reduced the development of acute lung inflammation on the basis of phosphorylation of NF-κB p65 in the lung.

Conclusion

These findings suggest the identification of ATR treatment for the lung inflammation induced by activating the complement system on the basis of its anti-inflammatory response. Together with the model replicating the complement activating characteristics of acute lung injury, the results may be translatable to the overactivated complement relevant diseases.
Correction to: Content validation of the EORTC QLQ-C15-PAL with advanced cancer patients and health care professionals from palliative care services in Chile
Authors: Rojas-Concha Leslye , Hansen Maiken Bang , Petersen Morten Aagaard , Groenvold Mogens
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Development and validation of the cancer symptoms discrimination scale: a cross-sectional survey of students in Yunnan, China
Authors: Feng Lin-sen , Dong Zheng-jiao , Yan Ruo-yu , Tu Chang-ling , Zhang Lan-yu , Shen Jiang-yun , Zhang Shi-yu
Published: October 2020

Background

This study aimed to devise a Cancer symptoms Discrimination Scale (CSDS) suitable for China based on a cross-sectional survey.

Methods

The CSDS was developed using the classical measurement theory. A total of 3610 students from Yunnan province, China, participated in the cross-sectional survey. The test version of the scale was modified by the item analysis method, and after the official version of CSDS was developed, its reliability and validity were verified. A univariate analysis of variance and a multiple linear regression model were used to analyze the influencing factors of cancer symptoms discrimination among the university/college students.

Results

There were 21 items in total for the CSDS, including 3 subscales --- common clinical manifestations (11 items), physical appearance defects (6 items), and drainage tube(s) wearing (4 items). This CSDS had good validity (GFI = 0.930, AGFI = 0.905, RMR = 0.013, I-CVIs> 0.80, and the Pearson correlation coefficient was satisfactory.) and reliability (Cronbach’s alpha = 0.862, spearman-brown coefficient = 0.875). The multiple linear regression showed that certain factors may affect the students’ discrimination level against cancer symptoms (P < 0.05), including gender, major, current education degree, guardian’s highest record of formal schooling, self-rated health status, history of care for cancer patients, family relationship, ways of cancer knowledge acquisition, good/poor understanding of cancer-related information, degree of cancer fear, and their perception of cancer infectiousness.

Conclusion

This CSDS, with good reliability and validity, can be used for the evaluation of the discrimination risk and levels against cancer symptoms among healthy students.
A german-language competency-based multisource feedback instrument for residents: development and validity evidence
Authors: Hennel Eva K. , Subotic Ulrike , Berendonk Christoph , Stricker Daniel , Harendza Sigrid , Huwendiek Sören
Published: October 2020

Background

In medical settings, multisource feedback (MSF) is a recognised method of formative assessment. It collects feedback on a doctor’s performance from several perspectives in the form of questionnaires. Yet, no validated MSF questionnaire has been publicly available in German. Thus, we aimed to develop a German MSF questionnaire based on the CanMEDS roles and to investigate the evidence of its validity.

Methods

We developed a competency-based MSF questionnaire in German, informed by the literature and expert input. Four sources of validity evidence were investigated: (i) Content was examined based on MSF literature, blueprints of competency, and expert-team discussions. (ii) The response process was supported by analysis of a think-aloud study, narrative comments, “unable to comment” ratings and evaluation data. (iii) The internal structure was assessed by exploratory factor analysis, and inter-rater reliability by generalisability analysis. Data were collected during two runs of MSF, in which 47 residents were evaluated once (first run) or several times (second and third run) on 81 occasions of MSF. (iv) To investigate consequences, we analysed the residents’ learning goals and the progress as reported via MSF.

Results

Our resulting MSF questionnaire (MSF-RG) consists of 15 items and one global rating, which are each rated on a scale and accompanied by a field for narrative comments and cover a construct of a physician’s competence. Additionally, there are five open questions for further suggestions. Investigation of validity evidence revealed that: (i) The expert group agreed that the content comprehensively addresses clinical competence; (ii) The response processes indicated that the questions are understood as intended and supported the acceptance and usability; (iii) For the second run, factor analysis showed a one-factor solution, a Cronbach’s alpha of 0.951 and an inter-rater reliability of 0.797 with 12 raters; (iv) There are indications that residents benefitted, considering their individual learning goals and based on their ratings reported via MSF itself.

Conclusions

To support residency training with multisource feedback, we developed a German MSF questionnaire (MSF-RG), which is supported by four sources of validity evidence. This MSF questionnaire may be useful to implement MSF in residency training in German-speaking regions.
Comparative analysis of resource utilization in integrative anthroposophic and all German pediatric inpatient departments
Authors: Fetz Katharina , Längler Alfred , Schwermer Melanie , Carvalho-Hilje Clara , Vagedes Jan , Zuzak Tycho Jan , Ostermann Thomas
Published: October 2020

Background

Integrative Medicine (IM) combines conventional and complementary therapies. It aims to address biological, psychological, social, spiritual and environmental aspects of patients’ health. During the past 20 years, the use and request of IM in children and adults has grown.

Anthroposophic Medicine (AM) is an IM approach frequently used in children in Germany. From both public health and health economic perspectives, it is relevant to investigate whether there are differences in the resource utilization between integrative pediatric departments (IPD) and the entirety of all pediatric departments.

Methods

Standard ward documentation data from all German integrative anthroposophic pediatric departments (2005–2016;N = 29,956) is investigated and systematically compared to data of the entirety of all pediatric departments in Germany derived from the Institute for the Hospital Reimbursement System (2005–2016,N = 8,645,173). The analyses focus on: length of stay, Diagnosis Related Groups (DRG), Major Diagnosis Categories (MDC), and effective Case Mix Index (CMI).

Results

The length of stay in the IPD (M = 5.38 ± 7.31) was significantly shorter than the DRG defined length of stay (M = 5.8 ± 4.71;p < .001; d = − 0.07) and did not exceed or undercut the DRG covered length of stay. Compared to the entirety of all pediatric departments (M = 4.74 ± 6.23) the length of stay was significantly longer in the in the IPD (p<. 001; d = 0.12). The effective CMI in IPD and all pediatric departments were identical (M = 0.76). The frequencies of DRG and MDC differed between IPD and all pediatric departments, with higher frequencies of DRGs and MDCs associated with chronic and severe illnesses in the IPD.

Conclusions

Treatment within integrative anthroposophic pediatric departments fits well in terms of the DRG defined conditions concerning length of stay, even though integrative pediatric patients has an increased length of stay of averagely 1 day, which is most likely associated to time consuming, complex integrative treatment approaches and to a certain extend to higher amount of chronic and severe diseases.
Impact of DRGs-based inpatient service management on the performance of regional inpatient services in Shanghai, China: an interrupted time series study, 2013–2019
Authors: Feng Lvfan , Tian Yuan , He Mei , Tang Jie , Peng Ying , Dong Chenjie , Xu Wenzhong , Wang Tao , He Jiangjiang
Published: October 2020

Background

The asymmetry of information brings difficulty for government to manage public hospitals. Therefore, Jiading District of Shanghai has been establishing DRGs-based inpatient service management system (ISMS) to effectively compare the output of different hospitals through DRGs, reward desired hospital performance and enhance inpatient service capacity. However, the impact of the implementation of DRGs-based inpatient service management (ISM) policy in Jiading district is still unknow. We therefore conducted this study to evaluate the impact of DRGs-based ISM policy on the performance of inpatient service since its implementation in Jiading District, Shanghai, China in 2017.

Methods

Using an interrupted time series design, we analyzed quarterly data of seven DRGs-based performance measures from the ISMS which covered all five public hospitals in Jiading District from 2013 to 2019. We utilized the segmented linear regression model to assess the change of level and trend of performance indicators before and after ISM policy. Dickey–Fuller test was used to examine the stationary of the data. Durbin-Watson test was performed to check the series autocorrelation of indicators.

Results

Significant changes in the following indicators were observed since the implementation of ISM policy. The case-mix index (CMI) level decreased by 0.103 (P < 0.05), the trend increased by 0.008 (P < 0.05). The total weight level decreased by 3719.05 (P < 0.05), and the trend increased by 250.13 (P < 0.05). The time efficiency index (TEI) level increased by 0.12 (P < 0.05), and the trend decreased by 0.01 (P < 0.05). The cost efficiency index (CEI) level increased by 0.31 (P < 0.05), and the trend decreased by 0.02 (P < 0.05). No significant difference was found in the change of DRGs number, inpatient mortality of low-risk group cases (IMLRG) and inpatient mortality of medium-to-low risk group cases (IMMLRG).

Conclusions

Findings highlight the role of ISM policy in improving the capacity and efficiency of regional inpatient service. Three prerequisites, including a good information system, high-quality EMR data, and a management team, are needed for other countries to implement their own ISM policy to help government manage public hospitals and improve the performance of regional inpatient service.
Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis
Authors: Huang Donglan , Liu Qianqian , Zhang Weijun , Huang Chunyue , Zheng Ronghui , Xie Guofeng , Wang Hongmei , Jia Baochang , Shi Jianjun , Yuan Yawei , Deng Min
Published: October 2020

Background

Despite improvements in nasopharyngeal carcinoma (NPC) treatment, patients with recurrence and metastasis still have a poor prognosis. Thus, the identification of novel biomarkers is urgently needed to predict outcomes and tailor treatment for NPC.

Methods

Four data sets were downloaded from Gene Expression Omnibus, and one data set GSE68799 of which was applied to filtrate key modules and hub genes by construction of a co-expression network. Other data sets (GSE12452 and GSE53819) were used to verify hub genes. The data set GSE102349 was devoted to identify prognostic hub genes by survival analysis. To explored whether prognostic hub genes are related to hypoxia signatures in NPC, correlation analysis was carried out, and followed by functional verification experiments of those genes in vitro.

Results

By co-expression network analysis, blue module was regarded as a key module in the benign and malignant group, and IGSF9 of the blue module was identified as a prognostic hub gene. Moreover, IGSF9 is expected to be a innovative hypoxia-related gene in NPC based on the strong associativity between expression of IGSF9 and hypoxia scores of three signatures (99-gene, 26-gene and 15-gene). Further functional studies verified that down-regulated expression of IGSF9 could reduce the proliferation, migration and invasion ability of NPC cells, and hypoxia could induce the expression of IGSF9.

Conclusion

IGSF9 was identified to be relevant to prognosis and involved in hypoxia in NPC. IGSF9 might serve as one novel prognostic indicator of NPC in the future.
Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis
Authors: Liang Yahang , Shi Jingbo , He Qingsi , Sun Guorui , Gao Lei , Ye Jianhong , Tang Xiaolong , Qu Hui
Published: October 2020

Background

Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC.

Methods

qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo.

Results

Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB.

Conclusions

In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.
MiR-1307-5p targeting TRAF3 upregulates the MAPK/NF-κB pathway and promotes lung adenocarcinoma proliferation
Authors: Du Xinyue , Wang Shuangmiao , Liu Xingyan , He Tao , Lin Xiangui , Wu Simin , Wang Dan , Li Jiao , Huang Wenhua , Yang Huiling
Published: October 2020

Background

Non-small cell lung cancer (NSCLC) includes lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MicroRNA (miRNA) plays an important role in the regulation of post-transcriptional gene expression in animals and plants, especially in lung adenocarcinoma.

Methods

MiR-1307-5p is an miRNA with significant differences screened by the second generation of high-throughput sequencing in the early stage of our research group. In the current study, a series of in vitro and in vivo experiments were carried out. MiR-1307-5p mimic, miR-1307-5p inhibitor, and NC were transfected into A549 and H1299 lung adenocarcinoma cells. The correlation between miR-1307-5p and clinicopathological features in pathological samples was analyzed using a lung adenocarcinoma tissue microarray, and miR-1307-5p expression was detected by qPCR. CCK-8, EdU, colony formation, scratch test, and Transwell assays were used to observe cell proliferation and migration. Double luciferase assay, western blot, qPCR, and immunohistochemistry were employed in confirming the target relationship between miR-1307-5p and TRAF3. Western blotting was used to analyze the relationship between miR-1307-5p and the NF-κB/MAPK pathway. Finally, the effect of miR-1307-5p on tumor growth was studied using a subcutaneous tumorigenesis model in nude mice.

Results

Increased miR-1307-5p expression was significantly related to decreased overall survival rate of lung adenocarcinoma patients, revealing miR-1307-5p as a potential oncogene in lung adenocarcinoma. MiR-1307-5p mimic significantly promoted while miR-1307-5p inhibitor reduced the growth and proliferation of A549 and H1299 cells. MiR-1307-5p overexpression significantly enhanced the migration ability while miR-1307-5p inhibition reduced the migration ability of A549 and H1299 cells. Target binding of miR-1307-5p to TRAF3 was confirmed by double luciferase assay, western blot, qPCR, and immunohistochemistry. miR-1307-5p caused degradation of TRAF3 mRNA and protein. MiR-1307-5p targeted TRAF3 and activated the NF-κB/MAPK pathway. TRAF3 colocalized with p65 and the localization of TRAF3 and p65 changed in each treatment group. Tumor volume of the lv-miR-1307-5p group was significantly larger than that of the lv-NC group, and that of the lv-miR-1307-5p-inhibitor group was significantly smaller than that of the lv-NC group.

Conclusion

In conclusion, miR-1307-5p targets TRAF3 and activates the NF-κB/MAPK pathway to promote proliferation in lung adenocarcinoma.
Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria
Authors: Potluri Vijay , Shandil Radha K. , Gavara R. , Sambasivam Ganesh , Campo Brice , Wittlin Sergio , Narayanan Shridhar
Published: October 2020

Background

Emergence of anti-malarial drug resistance and perpetual increase in malaria incidence necessitates the development of novel anti-malarials. Histone deacetylases (HDAC) has been shown to be a promising target for malaria, despite this, there are no HDAC inhibitors in clinical trials for malaria treatment. This can be attributed to the poor pharmacokinetics, bioavailability and selectivity of the HDAC inhibitors.

Methods

A collection of HDAC inhibitors were screened for anti-malarial activity, and the best candidate was profiled in parasite-killing kinetics, growth inhibition of sensitive and multi-drug resistant (MDR) strains and against gametocytes. Absorption, distribution, metabolism and excretion pharmacokinetics (ADME-PK) parameters of FNDR-20123 were determined, and in vivo efficacy was studied in a mouse model for Plasmodium falciparum infection.

Results

A compound library of HDAC inhibitors (180 in number) was screened for anti-malarial activity, of which FNDR-20123 was the most potent candidate. The compound had been shown to inhibit Plasmodium HDAC with IC50 of 31 nM and human HDAC with IC50 of 3 nM. The IC50 obtained for P. falciparum in asexual blood-stage assay was 42 nM. When compared to atovaquone and pyrimethamine, the killing profiles of FNDR-20123 were better than atovaquone and comparable to pyrimethamine. The IC50 values for the growth inhibition of sensitive and MDR strains were similar, indicating that there is no cross-resistance and a low risk of resistance development. The selected compound was also active against gametocytes, indicating a potential for transmission control: IC50 values being 190 nM for male and > 5 µM for female gametocytes. FNDR-20123 is a stable candidate in human/mouse/rat liver microsomes (> 75% remaining post 2-h incubation), exhibits low plasma protein binding (57% in humans) with no human Ether-à-go–go-Related Gene (hERG) liability (> 100 µM), and does not inhibit any of the cytochrome P450 (CYP) isoforms tested (IC50 > 25 µM). It also shows negligible cytotoxicity to HepG-2 and THP-1 cell lines. The oral pharmacokinetics in rats at 100 mg/kg body weight shows good exposures (Cmax = 1.1 µM) and half-life (T1/2 = 5.5 h). Furthermore, a 14-day toxicokinetic study at 100 mg/kg daily dose did not show any abnormality in body weight or gross organ pathology. FNDR-20123 is also able to reduce parasitaemia significantly in a mouse model for P. falciparum infection when dosed orally and subcutaneously.

Conclusion

FNDR-20123 may be a suitable candidate for the treatment of malaria, which can be further developed.
High prevalence of asymptomatic malaria infections in adults, Ashanti Region, Ghana, 2018
Authors: Heinemann Melina , Phillips Richard O. , Vinnemeier Christof D. , Rolling Christina C. , Tannich Egbert , Rolling Thierry
Published: October 2020

Background

Ghana is among the high-burden countries for malaria infections and recently reported a notable increase in malaria cases. While asymptomatic parasitaemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce, and usually focus on children and on non-falciparum species. The present study aims to assess the prevalence of asymptomatic Plasmodium falciparum and non-falciparum infections in Ghanaian adults in the Ashanti region during the high transmission season.

Methods

Asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium species by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR. For all Plasmodium ovale infections additional sub-species identification was performed.

Results

Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with P. ovale. The sub-species P. ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with P. falciparum.

Conclusions

Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with P. malariae, P. o. curtisi and P. o. wallikeri.
Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways
Authors: He Bin , Li Qi Yue , Wu Yuan Yuan , Ruan Jing Ling , Teng Xiao Ming , Li Da Jin , Tang Chuan Ling
Published: October 2020

Background

Trophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies. Oxidative stress (OS) is an important inducer of trophoblast apoptosis. Cyclosporin A (CsA) has been shown to promote the activity of trophoblast cells and reduce OS-induced oxidative injury. We investigated the role and mechanism of CsA in oxidative stress-induced trophoblast cell apoptosis.

Methods

JEG-3 cells were cocultured with H2O2and CsA. Cell viability and morphology were measured by MTT assay and DAPI staining. Cell apoptosis was tested with annexin V/PI staining. The expression of Bcl-2-associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), cleaved poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 was assayed by western blotting. The protein expression and phosphorylation of p53 and mitogen-activated protein kinase (MAPK) kinases (JNK, ERK1/2 and p38) were examined by western blotting.

Results

CsA increased the viability, alleviated morphological injury and reduced cell apoptosis of the H2O2-treated JEG-3 cells. CsA also attenuated the activation of p53, decreased the expression of Bax and cleavage of PARP, and increased the expression of Bcl-2 and pro-caspase-3 in the JEG-3 treated with H2O2. Furthermore, CsA reduced the activation of JNK and P38 but had no significant effect on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the H2O2-treated JEG-3 cells. Promoting the activation of JNK and p38 impaired the protective effect of CsA on OS-induced trophoblast apoptosis.

Conclusions

These results suggested that CsA protected trophoblast cells from OS-induced apoptosis via the inhibition of the p53 and JNK/p38 signaling pathways.
Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis
Authors: Cao Weijie , Zheng Deqiang , Zhang Jie , Wang Anxin , Liu Di , Zhang Jinxia , Singh Manjot , Maranga Isinta Elijah , Cao Mingyang , Wu Lijuan , Song Manshu , Wang Wei , Wang Youxin
Published: October 2020

Background

Many contradictory conclusions pertaining to the telomere length in peripheral leukocyte chromosomes as a potential biomarker for ischemic stroke (IS) risk have been reported by the various observational studies in previous years. This study aims to investigate whether the leukocyte telomere length is associated with an increased IS risk or not, based on the Mendelian randomization (MR) approach.

Methods

Based on the NHGRI-EBI GWAS Catalog database, the Chinese online genetic database as well as the previous published studies, twelve single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05 were selected and the leukocyte telomere length was measured in 431 first-ever IS patients and 304 healthy controls (quantitative polymerase chain reaction). To explore linear and non-linear effect of telomere length on the IS risk, we preformed the linear MR analysis (the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method), and the non-linear MR analysis (semiparametric method with three tests for non-linearity, including the quadratic test, Cochran’s Q test, and the fractional polynomial test).

Results

Two verified SNPs (rs11125529 and rs412658) were chosen as instrumental variables. In linear MR analysis, the adjusted odds ratios and 95% confidence intervals of IS for genetically predicted telomere lengths, based on the two SNPs, were 1.312 (0.979 to 1.759), 1.326 (0.932 to 1.888) and 1.226 (0.844 to 1.781) for the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method, respectively. Three tests for nonlinearity failed to reject the null exactly, indicating that the relationship between telomere length and IS risk is unlikely to be non-linear.

Conclusion

This MR study based on individual data does not provide strong evidence for a positive linear or non-linear effect of telomere length on the IS risk.