bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing capacity of health facilities to provide routine maternal and newborn care in low-income settings: what proportions are ready to provide good-quality care, and what proportions of women receive it?
Authors: Tomlin Keith , Berhanu Della , Gautham Meenakshi , Umar Nasir , Schellenberg Joanna , Wickremasinghe Deepthi , Marchant Tanya
Published: April 2020

Background Good quality maternal and newborn care at primary health facilities is essential, but in settings with high maternal and newborn mortality the evidence for the protective effect of facility delivery is inconsistent. We surveyed samples of health facilities in three settings with high maternal mortality to assess their readiness to provide routine maternal and newborn care, and proportions of women using facilities that were ready to offer good quality care. Surveys were conducted in 2012 and 2015 to assess changes over time. Methods Surveys were conducted in Ethiopia, the Indian state of Uttar Pradesh and Gombe State in North-Eastern Nigeria. At each facility the staffing, infrastructure and commodities were quantified. These formed components of four “signal functions” that described aspects of routine maternal and newborn care. A facility was considered ready to perform a signal function if all the required components were present. Readiness to perform all four signal functions classed a facility as ready to provide good quality routine care. From facility registers we counted deliveries and calculated the proportions of women delivering in facilities ready to offer good quality routine care. Results In Ethiopia the proportion of deliveries in facilities classed as ready to offer good quality routine care rose from 40% (95% confidence interval (CI) 26-57) in 2012 to 43% (95% CI 31-56) in 2015. In Uttar Pradesh these estimates were 4% (95% CI 1-24) in 2012 and 39% (95% CI 25-55) in 2015, while in Nigeria they were 25% (95% CI 6-66) in 2012 and zero in 2015. Improved facility readiness in Ethiopia and Uttar Pradesh arose from increased supplies of commodities, while in Nigeria facility readiness fell due to depleted commodity supplies and fewer Skilled Birth Attendants. Conclusions This study quantified the readiness of health facilities to offer good quality routine maternal and newborn care, and may help explain inconsistent outcomes of facility care in some settings. Signal function methodology can provide a rapid and inexpensive measure of such facility readiness. Incorporating data on facility deliveries and repeating the analyses highlighted adjustments that could have greatest impact upon routine maternal and newborn care.
A comparison of the Indian Diet with the EAT-Lancet Reference Diet
Authors: Sharma Manika , Kishore Avinash , Roy Devesh , New Kuhu Joshi
Published: April 2020

Background The 2019 EAT-Lancet Commission report recommends healthy diets that can feed 10 billion people by 2050 from environmentally sustainable food systems. This study compares food consumption patterns in India, from different income groups and regions and sectors(rural/urban), with the EAT-Lancet reference diet and highlights the deviations. Methods The analysis was done using data from consumption expenditure survey of a nationally representative sample of 0.102 million households from 7469 villages and 5268 urban blocks of India by the National Sample Survey Organization (NSSO) in 2011-12. This is the most recent nationally representative data on household consumption in India. Calorie intake (kcal/capita/day) of food groups was calculated using quantity of consumption and nutritional values of food items from the NSSO report. Diet across rural and urban, poor and rich households across different regions were compared with EAT-Lancet reference diet. Results Average daily calorie consumption in India is below the recommended 2503 kcal/capita/day across all groups compared, except for the richest 5% of the population. Calorie share of whole grains is significantly higher than the EAT-Lancet recommendations while those of fruits, vegetables, legumes, and meat, fish & eggs are significantly lower. The share of calories from protein sources is only 6-8% in India compared to 29% in the reference diet. The imbalance is highest for the households in the lowest decile of consumption expenditure, but even the richest households in India do not consume adequate amounts of fruits, vegetables and non-cereal proteins in their diets. An average Indian household consumes more calories from processed foods than fruits. Conclusions Indian diets, across states and income groups, are unhealthy. Indians also consume excessive cereals and not enough proteins, fruits and vegetables. Importantly, unlike many countries, excess consumption of animal protein is not a problem in India. Indian policy-makers need to accelerate food system wide efforts to make healthier and sustainable diets more affordable, accessible and acceptable.
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

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

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

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

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

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

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

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

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

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

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

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.
RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human Laryngeal squamous cell carcinoma
Authors: shi xinli , Li Shenghao , Wang Li , Li Hui , Li Zhen , Wang Weiyi , Bai Jing , Sun Yajing , Li Jianchun , Li Xiaoming
Published: April 2020

Background Interferon-inducible 16 (IFI16) /caspase-1 inflammasome activates and secretes IL-1β. However, whether the IFI16 inflammasome involved in human Laryngeal squamous cell carcinoma is still unclear. Autophagy directly removed inflammasome components and limited early IL-1β production. RalB is required for the crosstalk between inflammasome and autophagy in macrophages. Dihydroartemisinin (DHA), the main derived ingredient of artemisinin, has a variety of biological activities. The mechanism of DHA in regulation the crosstalk between IFI16 inflammasome and autophagy by inhibiting RalB expression was analyzed in order to provide clues for new therapeutic methods in laryngeal cancer. Methods The expression of IFI16 was analyzed by Oncomine and GEPIA databases and detected by Western blot and immunohistochemistry. The relationship between IFI16 inflammasome and autophagy was investigated by transmission electron microscopy, immunofluorescence assay, etc. in Hep-2, Cal-27 and HeLa cells with DHA treatment. Hep-2 cell xenograft tumor in nude mice were used to assess the effect of DHA on laryngeal cancer. Results The study was firstly reported that IFI16 was overexpressed and positively correlated with caspase-1 in laryngeal carcinoma tissues. DHA alone or in combination with cisplatin significantly inhibited inflammasome activation and reduced IL-1β production in the xenograft tumor microenvironment of Hep-2 cell xenograft tumor in nude mice. Mechanistically, we found that DHA degraded RalB by inhibiting USP33 expression, leading to triggered autophagy. Meanwhile, enhanced autophagy can reduce the expression of RalB and USP33. Therefore, DHA depresses RalB, resulting in formation a positive feedback loop between USP33 and autophagy. Further, DHA promotes autophagy, which suppresses the IFI16/caspase-1 inflammasome activation and IL-1β production. Conclusions Therefore, our findings demonstrate that DHA may act as a RalB inhibitor to regulate the crosstalk between autophagy and IFI16/caspase-1 inflammasome, which inhibits IL-1β production in tumor microenvironment.
Physical activity measures in patients with myalgic encephalomyelitis/chronic fatigue syndrome: correlations between peak oxygen consumption, the physical functioning scale of the SF-36 questionnaire, and the number of steps from an activity meter
Authors: Campen C (Linda) MC van , Rowe Peter C , Verheugt Freek WA , Visser Frans C
Published: April 2020

Background most studies to assess effort intolerance in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have used questionnaires. Few studies have compared questionnaires with objective measures like an actometer or an exercise test. Therefore three measures of physical activity in ME/CFS patients, being the physical functioning scale (PFS) of the SF-36, the number of steps/day (Steps) of an actometer and the %peak VO 2 of a cardiopulmonary stress test were compared. Methods female ME/CFS patients were selected from a clinical database if the three types of measurements were available, and the interval between measurements was ≤ three months. Data of the three measures were compared by linear regression. Results in 99 female patients the three different measures were linearly, significantly and positively correlated (PFS vs Steps, PFS vs %peak VO 2 and Steps vs %peak VO 2 : all P<0.001). Subgroup analysis showed that the relations between the three measures were not different in patients with versus without fibromyalgia and with versus without a maximal exercise effort (RER≥1.1). In 20 patients re-evaluated for symptom worsening, the mean of all three measures was significantly lower (P<0.0001), strengthening the observation of the relations between them. Despite the close correlation a large variation was observed between the three measures in individual patients. Conclusions given the large variation in ME/CFS patients, the use of only one type of measurement is inadequate. Integrating the three modalities may be useful for patient care by detecting overt discrepancies and may aid study designs aimed at improving exercise capacity.
Proficiency testing for identifying underperforming students before postgraduate education: a longitudinal study
Authors: Andreou Vasiliki , Eggermont Jan , Gielis Guy , Schoenmakers Birgitte
Published: April 2020

Background

Cognitive competencies are widely used to evaluate medical students’ performance in postgraduate education. However, non-cognitive competencies equally play an important role in medical students’ future career. Efficient selection of medical students in GP training plays an important role in improving healthcare quality. The aim of this study was to examine quantitatively and qualitatively the validity of a multicomponent proficiency assessment tool for identifying underperforming students in cognitive and non-cognitive competencies, prior to entering postgraduate GP education.

Design

Longitudinal cohort study with quantitative and qualitative data.

Setting

894 medical GP students from 2016 to 2018 in four Flemish universities in Belgium registered to take a multicomponent proficiency-test before admission to postgraduate education.

Method

Data on students were obtained from a proficiency-test as a test-score and from traineeship mentors’ reports qualitatively. A thematic analysis was performed to analyze mentors’ reports. The lowest and highest score quartiles were compared. The relationship between test score and whether a student was labelled as underperforming was calculated with chi-square tests, and the effect estimate was calculated with odds ratios.

Results

In total, 849 students took the multicomponent proficiency-test during 2016-2018. Test scores were normally distributed. Five different descriptive labels were extracted from mentors’ reports considering both cognitive and non-cognitive competences.

Conclusion

Students that ranked in the lowest score quartile had a higher likelihood of being signaled as underperforming than students ranking in the highest score quartile. Therefore, a low score in the multicomponent proficiency-test could indicate the need for early remediating actions. This present study did not address reliability.
Integrated regulatory-metabolic network model reveals critical mechanism and potential targets for Hepatocellular Carcinoma
Authors: Xu Yi-Zhou , Zhang Hang , Yang Qiang-Zhen , Sun Ren-Liang , Wang Ke , Shi Yong-Yong , Wang Zhuo
Published: April 2020

Background HCC (Hepatocellular carcinoma), the predominant form of liver cancer, has long been the top three leading cause of death in cancer worldwide. Although researchers have spent lot of effort to identify molecular targets available for treatment, the high tumor heterogeneity makes it difficult to develop effective therapy options and the drug response remains low. Under this circumstance, the precise stratification strategies are more than required. However, previous researches generally focused on single biological level, such as genome, transcriptome, or proteome, and are not able to discover effective therapeutic targets, so the systematic study of both regulation and metabolism of HCC is needed. Methods In this paper, we use two different algorithms to reconstruct regulatory networks for both HCC and normal liver cells, then integrate them with corresponding metabolic models in order to discover TFs (transcriptional factors) affecting tumorigenesis. Furthermore, a machine learning algorithm is utilized to classify HCC samples, differentially expressed genes, altered metabolic reactions and biological pathways are identified in lowest overall survival (OS) rate sub-type compared to others. Results We classify TCGA-LIHC samples into three sub-types with significantly different OS rate, and this stratification strategy is validated in another independent dataset LIRI-JP. Then, we identify 5 key TFs affecting cancer cell growth and CREB3L3 is believed to be associated with poor prognosis. The comprehensive metabolic analysis on personalized metabolic models highlight 18 metabolic genes essential for tumorigenesis in all three sub-types of patients, besides, ACADSB and CMPK1 are highly possible to be strongly correlated with lower OS. Conclusions Among 20 metabolic genes identified through metabolic analysis, 15 of them have already been targeted by approved drugs according to DrugBank. In addition, miRNAs targeting key TFs and genes are also involved in well-known cancer related pathways. The multi-scale regulatory-metabolic model reveals the critical mechanism of HCC cell proliferation and suggests potential targets.
RNF180 mediates STAT3 activity by regulating the expression of RhoC via the proteasomal pathway in gastric cancer cells
Authors: Wu Zizhen , Liu Huifang , Sun Weilin , Du Yingxin , He Wenting , Guo Shiwei , Chen Liqiao , Zhao Zhenzhen , Wang Pengliang , Liang Han , Deng Jingyu
Published: April 2020

Background Ring finger protein 180 (RNF180) is an important member of the E3 ubiquitin ligase family. As a tumor suppressor gene, RNF180 is significantly associated with the prognosis of patients with gastric cancer (GC) and can inhibit the proliferation, invasion, and migration of GC cells. Signal transducer and activator of transcription 3 (STAT3) is considered one of the most common oncogenes in human cancers with a key role in GC progression. In this study, we explored the relationship between RNF180 and STAT3 in GC cells. Methods The RNF180 gene was significantly overexpressed to observe its regulatory activity on STAT3 and pSTAT3 in GC cells. We then explored the molecular signaling pathways by which RNF180 could potentially regulate STAT3 through transcriptomics and proteomics experiments. Results RNF180 overexpression could suppress STAT3 phosphorylation in GC cells. Ubiquitin label-free experiments showed that the ubiquitination level of Ras homolog gene family member C (RhoC) is significantly increased in GC cells transfected with an RNF180 expression vector (RNF180-GFP vector) compared with cells transfected with an empty vector (vehicle vector). We subsequently demonstrated that RNF180 could directly combine with RhoC and promote the ubiquitination and degradation of RhoC protein in GC cells. The phosphorylation level of STAT3 significantly decreased in GC cells after RhoC knockdown using small hairpin RNA(shRNA). Conclusions RNF180 could inhibit GC progression by reducing the phosphorylation of STAT3 via the ubiquitination and degradation of RhoC protein in GC cells. Thus, the protein may be considered a novel therapeutic target for patients with GC.
CircNOLC1 promotes epithelial ovarian cancer tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression
Authors: Chen Shuo , Wu Wu , Li Qian-hui , Xie Bu-min , Shen Fan , Du Yu-ping , Zong Zhi-hong , Wang Li-li , Wei Xiao-qing , Zhao Yang
Published: April 2020

Background: Circular RNAs (circRNAs) play important roles in cancer tumorigenesis and progression, and could represent prognostic biomarkers and therapeutic targets. Herein, we demonstrated the role of circNOLC1 in epithelial ovarian cancer (EOC). Methods: CircNOLC1 expression was quantified in ovarian cancer tissues and normal ovarian tissues using quantitative real-time reverse transcriptase. After circNOLC1 overexpression or downregulation using a circNOLC1 overexpression plasmid or circNOLC1 short hairpin RNA (shRNA) transfection, respectively, ovarian cancer cell phenotypes and molecular mechanisms were examined in vivo and in vitro. Results: Circ-NOLC1 expression was higher in EOC tissues than in normal tissues, and was positively associated with FIGO stage, differentiation. Among ovarian cancer cell lines, circ-NOLC1 expression was highest in A2780, and lowest in CAOV3. Overexpression of circ-NOLC1 in CAOV3 cells increased cell proliferation, migration, and invasion, while silencing of circ-NOLC1 in A2780 cells had the opposite effect: however, neither circ-NOLC1 downregulation nor overexpression influenced nucleolar and coiled-body phosphoprotein 1 ( NOLC1 ) mRNA expression. In nude mice with subcutaneous tumors, circ-NOLC1 downregulation decreased tumor growth . Bioinformatic analysis and RNA binding protein immunoprecipitation showed that circNOLC1 could bind to epithelial splicing regulatory protein 1 (ESRP1). In addition, circ-NOLC1 overexpression significantly increased ESRP1 protein levels, and those of ras homolog family member A (RhoA) and cyclin dependent kinase 1 (CDK1); circNOLC1 downregulation had the opposite effects. The tumor-promoting effect of circNOLC1 was inhibited by knockdown of ESRP1 expression in circ-NOLC1 overexpressing cells, which might act by modulating RhoA and CDK1 expression. Conclusion: CircNOLC1 might promote EOC tumorigenesis and development by binding ESRP1 and modulating CDK1 and RhoA expression.
Catechin and Curcumin interact with corona (2019-nCoV/SARS-CoV2) viral S protein and ACE2 of human cell membrane: insights from Computational study and implication for intervention
Authors: Jena Atala B. , Kanungo Namrata , Nayak Vinayak , Chainy G.B.N. , Dandapat Jagneshwar
Published: April 2020

The recent outbreak of the coronavirus (2019n-CoV) is an unprecedented threat for human health throughout the globe. In this regards development of a suitable intervention is the need of the hour. The viral spike protein (S-Protein) and the cognate host cell receptor ACE2 can prove to be effective. Here, through computational approaches we have reported two polyphenols, Catechin and Curcumin which have dual binding affinity i.e both the molecule binds to viral S-protein and as well as ACE2. Catechin binds with S-protein and ACE2 with binding energy of -10.5 Kcal/mol and -8.9 Kcal/mol, respectively. Catechin binds with a greater affinty than that of curcumin which has a binding energy of -7.9Kcal/mol and - 7.8Kcal/mol for S-protein and ACE2, respectively. While curcumin gets bound directly to receptor binding domain (RBD) of viral S-protein, catechin binds to near proximity of RBD sequence of S-protein. Molecular simulation study demonstrates that curcumin directly binds with RBD site of S-protein during 40-100ns. In contrast, catechin binds with S-protein near the RBD site and causes fluctuation in the amino acids present in the RBD and it’s near proximity. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols, for therapeutic/preventive intervention.
Contact network analysis of patients with Novel Coronavirus Pneumonia - Based on 237 cases in Shaanxi Province
Authors: Zhangbo Yang
Published: April 2020

The spread of novel coronavirus is closely related to the structure of human social networks. Based on 237 cases in Shaanxi Province, using epidemiological retrospective statistics, data visualization, and social network analysis methods, this paper summarized characteristics of patients with new coronary pneumonia in Shaanxi Province, and analyzes these patients’ dynamic contact network structure. The study found that there are many clustered infections through strong ties, about one-third cases are caused by relatives' infection. In the early stages of the epidemic, it was mainly imported cases, and in the later stages, it was mainly local infection cases. The infected people were mainly middle-aged men. Symptoms of imported cases occurred on average 3 days after they arrived, and medical measures were taken on average 5 days later. All cases showed symptoms in less than 2 days on average and were then taken to medical treatment. The virus contact network can be divided into multiple disconnected components. The largest component has 12 patients. The average degree centrality in the network is 0.987. The average betweenness degree is 0. The average closeness degree is 0.452. The average PageRank index is 0.0042. The number of contacts of patients is unevenly distributed in the network.
Study on spatial distribution of pollutants and total amount reduction in the Duliujian River (Tianjin, China)
Authors: Liu Qiongqiong , Liu Dan , Zhang Yan , Wang Yanxi , Xing Meinan
Published: April 2020

The Duliujian River is the largest river in the downstream area of the Haihe River. In order to further clarify the main pollutant load and load contribution of the basin, and analyze the watershed pollution control unit, key pollution sources and their spatial distribution characteristics, this study divides the control unit of the basin, which is based on the digital elevation model (DEM), and applies the expansion template of Arc Map–Arc Hydro tools software. On the basis of water environment capacity and total maximum daily load (TMDL) theory, water quality standards are set in accordance with the requirements of the water body function. Considering seasonal influence and the pollution load contribution rate, a total pollution load control plan and a load optimization allocation plan are proposed, in order to realize the distribution of pollution load among point source, non-point source and safety margin. According to the calculations, TMDL of chemical oxygen demand (COD) and NH3-N in the flood season (June–September) in the Duliujian River is the largest, about 27,005 kg/d and 2,296 kg/d, respectively. During the dry season (December–March), the reduction of COD and NH3-N is the largest, reaching 50.74% and 90.14%, respectively. And Duliujian River is dominated by non-point source pollution.