bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable high frequencies of sulfadoxine-pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine-pyrimethamine in Ujjain, Madhya Pradesh, India
Authors: Pathak Ashish , Mårtensson Andreas , Gawariker Sudhir , Sharma Ashish , Diwan Vishal , Purohit Manju , Ursing Johan 
Published: April 2020

Abstract
Background Artesunate plus sulfadoxine-pyrimethamine (ASP) are first line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimathamine were 9% and >80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015-2016 after 3-4 years of ASP use, are reported. Methods Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16-185, pfdhps 436-632 and K13 407-689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism. Results Sulfadoxine-pyrimethamine resistance-associated pfdhfr 108N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R+108N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively. Conclusion The frequency of P. falciparum with reduced susceptibility to sulfadoxine-pyrimethamine remained high but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use.
Strain pattern of each ligamentous band of the superficial deltoid ligament: a cadaver study
Authors: Takao Masato , Ozeki Satoru , Oliva Xavier Martin , Inokuchi Ryota , Yamazaki Takayuki , Takeuchi Yoshitaka , Kubo Maya , Lowe Danielle , Matsui Kentaro , Katakura Mai , Glazebrook Mark 
Published: April 2020

Abstract
BackgroundThere are few reports on the detailed biomechanics of the deltoid ligament, and no studies have measured the biomechanics of each ligamentous band because of the difficulty in inserting sensors into the narrow ligaments. This study aimed to measure the strain pattern of the deltoid ligament bands directly using a Miniaturization Ligament Performance Probe (MLPP) system.MethodsThe MLPP was sutured into the ligamentous bands of the deltoid ligament in 6 fresh-frozen lower extremity cadaveric specimens. The strain was measured using a round metal disk (clock) fixed on the plantar aspect of the foot. The ankle was manually moved from 15° dorsiflexion to 30° plantar flexion, and a 1.2-N-m force was applied to the ankle and subtalar joint complex. Then the clock was rotated every 30° to measure the strain of each ligamentous band at each endpoint.ResultsThe tibionavicular ligament (TNL) began to tense at 10° plantar flexion, and the tension becomes stronger as the angle increased; the TNL worked most effectively in plantar flex-abduction. The tibiospring ligament (TSL) began to tense gradually at 15° plantar flexion, and the tension became stronger as the angle increased. The TSL worked most effectively in abduction. The tibiocalcaneal ligament (TCL) began to tense gradually at 0° dorsiflexion, and the tension became stronger as the angle increased. The TCL worked most effectively in pronation (dorsiflexion-abduction). The superficial posterior tibiotalar ligament (SPTTL) began to tense gradually at 0° dorsiflexion, and the tension became stronger as the angle increased, with the SPTTL working most effectively in dorsiflexion.ConclusionOur results show the biomechanical function of the superficial deltoid ligament and may contribute to determining which ligament is damaged during assessment in the clinical setting.
An investigation of genetic polymorphisms in Heparan Sulfate Proteoglycan core proteins and key modification enzymes in an Australian Caucasian multiple sclerosis population
Authors: Okolicsanyi Rachel K , Bluhm Julia , Miller Cassandra , Griffiths Lyn R , Haupt Larisa M 
Published: April 2020

Abstract
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system in young adults. Heparan sulfate proteoglycans (HSPGs) are ubiquitous to the cell surface and the extracellular matrix. HSPG biosynthesis is a complex process involving enzymatic attachment of heparan sulfate (HS) chains to a core protein. HS side chains mediate specific ligand and growth factor interactions directing cellular processes including cell adhesion, migration and differentiation. Two main families of HSPGs exist, the syndecans (SDC1-4) and glypicans (GPC1-6). The SDCs are transmembrane proteins, while the GPC family are GPI-linked to the cell surface. SDC1 has well-documented interactions with numerous signalling pathways. Genome wide association studies (GWAS) have identified regions of the genome associated with MS including a region on chromosome 13 containing GPC5 and GPC6. International studies have revealed significant associations between this region and disease development. The exostosin-1 (EXT1) and sulfatase-1 (SULF1) are key enzymes contributing to the generation of HS chains. EXT1, with documented tumour suppressor properties, is involved in initiation and polymerisation of the growing HS chain. SULF1 removes 6- O -sulfate groups from HS chains, affecting protein-ligand interactions and subsequent downstream signalling with HS modification potentially having significant effects on MS progression. In this study we identified significant associations between single nucleotide polymorphisms in SDC1, GPC5 and GPC6 and MS in an Australian Caucasian case control population. Further significant associations in these genes were identified when the population was stratified by sex and disease subtype. No association was found for EXT1 or SULF1.
Bacterial Typing and Identification Based on Fourier Transform Infrared Spectroscopy
Authors: Yang Huayan , Wu Fangling , Xu Fuxin , Tang Keqi , Ding Chuanfan , Shi Haimei , Yu Shaoning 
Published: April 2020

Abstract
Fourier transform infrared (FT-IR) spectroscopy is a label-free and highly sensitive technique that provides complete information on the chemical composition of biological samples. The bacterial FT-IR signals are extremely specific and highly reproducible fingerprint-like patterns, making FT-IR an efficient tool for bacterial typing and identification. Due to the low cost and high flux, FT-IR has been widely used in hospital hygiene management for infection control, epidemiological studies, and routine bacterial determination of clinical laboratory values. However, the typing and identification accuracy could be affected by many factors, and the bacterial FT-IR data from different laboratories are usually not comparable. A standard protocol is required to improve the accuracy of FT-IR-based typing and identification. Here, we detail the principles and procedures of bacterial typing and identification based on FT-IR spectroscopy, including bacterial culture, sample preparation, instrument operation, spectra collection, spectra preprocessing, and mathematical data analysis. Without bacterial culture, a typical experiment generally takes <2 h.
The anti-inflammatory mechanism of berberine on lipopolysaccharide-induced IEC-18 models based on comparative transcriptomics
Authors: Xu xiaofan , Zhang Le , Zhao Ya , Xu Baoyang , Qin Wenxia , Yan Yiqin , Yin Boqi , Xi Chuyu , Ma Libao 
Published: April 2020

Abstract
Background Intestinal surface epithelial cells (IECs) have long been considered an effective barrier for maintaining water and electrolyte balance and participating in the absorption of nutrients. When intestinal inflammation occurs, IECs tend to malfunction. Berberine (BBR) is an isoquinoline alkaloid found as the major alkaloid in many medicinal plants, which has been clinically used in China to treat gastrointestinal pathogenic bacterial infection, especially bacteria-induced diarrhea and inflammation. Methods We treated rat intestinal epithelial cells IEC-18 with lipopolysaccharide to establish an in vitro model of epithelial cell inflammation and used berberine to treat the cells in order to explore the anti-inflammatory mechanism of berberine. We then used transcriptome data to find the differentially expressed genes (DEGs) in each group, and analyzed DEGs by GO, KEGG, WGCNA and IPATH to find the functions and pathways enriched by DEGs. Finally, we used q-pcr to vertify our transcriptome dates. Results We found DEGs between LPS and LPS+BBR groups are enriched in DNA replication, cell cycle, apoptosis, leukocyte migration, NF-κB and Ap-1pathway. The results showed berberine can restrict DNA replication, inhibits cell cycle and promote apoptosis. It can also inhibit the traditional inflammatory pathways such as NF-κB, Ap-1 and the expression of various chemokines to prevent the migration of leukocyte. Conclusion According to our transcriptomics dates, berberine can exert anti-inflammatory effect by regulating a variety of cellular physiological activities like cell cycle, apoptosis, inflammation pathways and leukocyte migration.
Effect of psychological characteristics and malocclusion severity on compliance of removable orthodontic appliances by 10-12-year-old orthodontic patients: A research article
Authors: Naseri Navid , Bassagh Niloofar , Baherimoghadam Tahereh , Hashemi Zahra , Bassagh Elmira 
Published: April 2020

Abstract
Background : Treatment compliance plays fundamental roles in achieving the best results in orthodontic treatment. Some psychological characteristics such as general self-efficacy (GSE) are correlated with the level of tolerance of individuals. This study aimed to assess the correlation of psychological characteristics such as GSE and level of malocclusion with compliance of removable orthodontic appliances. Methods : The Index of Orthodontic Treatment Need (IOTN) of 50 patients between 10-12 years who required removable orthodontic appliances was determined prior to the onset of treatment. They were also requested to fill out the GSE scale (GSES). The removable orthodontic appliance compliance questionnaire was also filled out by patients at 1 (T1), 3 (T2), and 6 (T3) months after the delivery of the removable orthodontic appliance. Results : The GSES score had significant correlations with the total score of the compliance questionnaire, and subscale score of satisfaction with the appliance during eating and oral hygiene practice, duration of usage of the appliance, and interest in using it (P<0.05). The IOTN had no significant correlation with the compliance questionnaire. Conclusions: The level of compliance of removal orthodontic appliances by patients can be predicted using the GSES. The IOTN is not efficient for prediction of the compliance level of removal orthodontic appliances by patients.
Cardio-metabolic risk factors among patients with tuberculosis attending tuberculosis treatment centers in Nepal
Authors: Poudyal Indra Prasad , Khanal Pratik , Mishra Shiva Raj , Malla Milan , Poudel Prakash , Jha Raj Kumar , Phuyal Anil , Barakoti Abiral , Adhikari Bipin 
Published: April 2020

Abstract
Background The co-morbidity of cardio-metabolic diseases in patients with Tuberculosis adds a significant burden in current health systems in developing countries including Nepal. The main objective of this study was to explore cardio-metabolic risk factors among patients with Tuberculosis. Methods This was a cross-sectional study conducted in 12 tuberculosis centers from eight districts of Nepal between May and July 2017. A total of 238 patients with tuberculosis who visited Tuberculosis centers for Directly Observed Treatment Short-course therapy participated in this study. Interviews with participants were conducted using a structured questionnaire and were supplemented by anthropometric measurements and on site blood glucose tests. Data were analyzed using descriptive and inferential statistics. Results Among 221 study participants, 138 (62.4%) had new smear positive pulmonary tuberculosis, 24 (10.9%) had new smear negative pulmonary tuberculosis and 34 (15.4%) had new extra pulmonary tuberculosis. Overall, 43.1% of the patients with tuberculosis had at least one cardio-metabolic risk factor. The prevalence of at least one cardio-metabolic risk factor was more in male than female (47.8% versus 33.8%). Prevalence of tobacco (18.9% versus 4.8%), and alcohol (12.6% versus 6.5%) use was proportionately higher in male compared to female. The prevalence of hypertension (17% vs. 21%) and obesity (11.9% vs. 12.9%) was lower in male compared to females. Female (AOR=0.47; CI: 0.23-0.94), those from Gandaki Province (AOR=0.32; CI: 0.13-0.79) and literate (AOR=0.49; CI: 0.25-0.96) had reduced risk of cardio-metabolic disease risk factors. Conclusions This study highlights the role of gender and socio-demographic characteristics associated with the risk of cardio-metabolic diseases in patients with Tuberculosis. The findings from this study can guide medical practitioners and policy makers to consider clinical suspicion, diagnosis and treatment. National treatment guideline can benefit by integrating the management of non-communicable diseases in Tuberculosis treatment centers.
Trends and seasonality in cause-specific mortality among children under 15 years in Guangzhou, China, 2008-2018
Authors: Xu Xiao-Han , Dong Hang , Li Li , Liu Wen-Hui , Lin Guo-Zhen , Ou Chun-Quan 
Published: April 2020

Abstract
Background: This study analyzed the trends and seasonality in mortality among children aged 0-14 years in Guangzhou, China during 2008-2018. Understanding the epidemiology of this public health problem can guide policy development for children mortality prevention.Methods: A population-based epidemiological retrospective study was conducted. 7,265 individual data of children mortality were obtained from the Guangzhou Centre for Disease Control and Prevention. The Poisson regression was used to quantify the annual average reduction rate and the difference in mortality rate between gender and age groups. Incidence ratios with 95% confidence intervals (CI) were calculated to determine the ratio of the observed number of deaths to the expected deaths (i.e. the average assuming no variations) by month, season, school term, weeks and holidays deaths.Results: Between 2008 and 2018, the children mortality rate in Guangzhou decreased from 54.0 to 34.3 per 100,000 children, with an annual reduction rate of 4.6% (95%CI: 1.1%-8.1%), especially the under-5 mortality rate decreased by 8.3% (95%CI: 4.8%-11.6%) per year. The decline trend varied by causes of death, even with an upward trend for the mortality of asphyxia and neurological diseases. The risk of death among male children was 1.78 times (95%CI: 1.61-1.98) that of females. The distribution of causes of death differed by age groups. Maternal and perinatal, congenital and pneumonia were the top three causes of death in infants and cancer accounted for 17% of deaths in children aged 1-14 years. Moreover, the injury-related mortality showed significant temporal variations with higher risk during the weekend. And there was a summer peak for drowning and a winter peak for asphyxia. Conclusions: Guangzhou has made considerable progress in reducing mortality over the last decade. The findings of characteristics of children mortality would provide important information for the development and implementation of integrated interventions targeted specific age groups and causes of death.
Analyses of the clinical features and contributing factors in 13 fatal cases of Coronavirus Disease 2019
Authors: Liu Haichao , Hu Zhenhong , Mao Chongzheng , Xu Ruijuan , Zhang Fangqi , Li Long , Song Qing 
Published: April 2020

Abstract
Objective To investigate the clinical features of and contributing factors in 13 fatal cases of Coronavirus Disease 2019 (COVID-19).Methods The clinical data of 13 patients who died of COVID-19 in Central Theater General hospital, China, between January 4, 2020, and February 24, 2020, were analyzed retrospectively. The data reviewed included clinical manifestations, laboratory test results and radiographic features. The cellular immune function and the expression of inflammatory factors in deceased patients at different stages of the disease were analyzed, and the clinical data and laboratory test results between the deceased group and the moderate group (20 patients), severe group (20 patients) and the critical group (10 patients) were compared.Results Of those who died, the patients consisted of 10 men and 3 women. The average age of those who died was (74±19) years, and 10 patients were over 70 years old (76.9%), which was significantly higher than the ages of patients in the moderate group, severe group and critical group. There were no significant differences in sex ratio and clinical manifestations among the 4 groups. For the patients who died, 9presented with underlying diseases,6 of whom had more than 2 diseases, which was significantly higher than the number of underlying disease in the other groups. On admission, the chest computed tomography (CT) for 8 patients (61.5%) mainly showed multiple patchy ground-glass opacities. When the disease progressed, the ground-glass opacities rapidly developed into diffuse lesions in both lungs. The lymphocyte and CD3 + ,CD4 + , and CD8 + T lymphocyte counts in the peripheral blood of 13 patients were significantly lower than normal levels and decreased more substantially during the disease course based on the levels when admitted (P<0.01). Additionally, the IL-6, D-dimer, C-reactive protein (CRP), lactic acid levels gradually increased, and most peaked before death. There were statistically significant differences in IL-6 expression, lymphocyte count and T lymphocyte subset count between the deceased group and the moderate group, severe group and critical group (P<0.01). However, there were no statistically significant differences in serum CRP lactic acid levels among the 4 groups (P>0.05).The cause of death for most patients was acute respiratory distress syndrome (ARDS) with type I respiratory failure. Three patients eventually developed multiorgan deficiency syndrome (MODS).Conclusion The risk factors of death for COVID-19 patients included older men, more underlying diseases, poor cellular immune function and overexpression of inflammatory factors. The main cause of death in patients with COVID-19 was ARDS, which led to respiratory failure and MODS.
Usefulness of Tissue Doppler-derived Atrial Electromechanical Delay for Identifying Patients with Paroxysmal Atrial Fibrillation
Authors: Akamatsu Kanako , Ito Takahide , Miyamura Masatoshi , Kanzaki Yumiko , Sohmiya Koichi , Hoshiga Masaaki 
Published: April 2020

Abstract
Background: Tissue Doppler imaging (TDI)-derived atrial electromechanical delay (AEMD), has been reported to be useful for predicting development of atrial fibrillation (AF). However, its usefulness remains unknown when analyzed along with patients seemingly at high-risk for AF as controls. From this standpoint, we investigated whether AEMD would be of use for identifying patients with paroxysmal AF (PAF). Methods: We analyzed TDI recordings to obtain AEMD in 73 PAF patients. Thirty-nine patients with multiple cardiovascular risk factors (MRFs) but without history of AF and 61 healthy individuals served as disease and healthy controls, respectively. AEMD was defined as the time-interval between the electrocardiogram P-wave and the beginning of the spectral TDI-derived A’ for the septal (septal EMD) and lateral (lateral EMD) sides of the mitral annulus. Results: There was no significant difference in the left atrial volume index between PAF patients and disease controls (28 ± 5 mL/m2 vs. 27 ± 5 mL/m2). PAF patients had longer AEMD, particularly for the lateral EMD (78 ± 26 ms), compared with disease (62 ± 21 ms, P = 0.003) and healthy (53 ± 24 ms, P <0.001) controls. Multivariate logistic regression analysis revealed that the lateral EMD (OR 1.42, 95%CI 1.16 – 1.75, P <0.001), along with the left atrial volume index (OR 2.86, 95%CI 1.70 – 4.80, P <0.001), was one of the significant independent associates of identifying PAF　patients. Conclusions: According to our data, analyzed along with MRFs patients, AEMD seems to be a useful index of identifying patients at risk for AF.
IFI6 depletion inhibits esophageal squamous cell carcinoma progression through reactive oxygen species accumulation via mitochondrial dysfunction and endoplasmic reticulum stress
Authors: Liu Zhenchuan , Lu Tiancheng , Wu Kaiqin , Gu Shaorui , Li Lei , Dong Cunlai , zhou yongxin 
Published: April 2020

Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal forms of adult cancer with poor prognosis. Substantial evidence indicates that reactive oxygen species (ROS) are important modulators of aggressive cancer behavior. However, the mechanism by which ESCC cells integrate redox signals to modulate carcinoma progression remains elusive. Methods: The expression of interferon alpha inducible protein 6 (IFI6) in clinical ESCC tissues and cell lines was detected by RT-PCR and Western blotting. The correlation between IFI6 expression levels and aggressive ESCC disease stage was examined by immunohistochemistry. Bioinformatic analysis was conducted to explore the potential function of IFI6 in ESCC. ESCC cell lines stably depleted of IFI6 and ectopically expressing IFI6 were established using lentiviruses expressing shRNAs and an IFI6 expression plasmid, respectively. The effects of IFI6 on ESCC cells were determined by cell-based analyses, including EdU assay, apoptotic assay, cellular and mitochondria-specific ROS detection, seahorse extracellular flux, and mitochondrial calcium flux assays. Blue native-polyacrylamide gel electrophoresis was used to determine mitochondrial supercomplex assembly. Transcriptional activation of NADPH oxidase 4 (NOX4) via ATF3 was confirmed by dual luciferase assay. In vivo tumor growth was determined in mouse xenograft models. Results: We find that the expression of IFI6, an IFN-stimulated gene localized in the inner mitochondrial membrane, is markedly elevated in ESCC patients and a panel of ESCC cell lines. High IFI6 expression correlates with aggressive disease phenotype and poor prognosis in ESCC patients. IFI6 depletion suppresses proliferation and induces apoptosis by increasing ROS accumulation. Mechanistically, IFI6 ablation induces mitochondrial calcium overload by activating mitochondrial Ca 2+ uniporter and subsequently ROS production. Following IFI6 ablation, mitochondrial ROS accumulation is induced by mitochondrial supercomplex assembly suppression and oxidative phosphorylation dysfunction, while IFI6 overexpression produces the opposite effects. Furthermore, energy starvation induced by IFI6 inhibition drives endoplasmic reticulum stress, which upregulates NOX4-derived ROS production in an ATF3-dependent manner. Finally, the results in xenograft models of ESCC further corroborate the in vitro findings. Conclusion: Our study unveils a novel redox homeostasis signaling pathway that regulates ESCC pathobiology and identifies IFI6 as a potential druggable target in ESCC.