bluuebunny/crossref_metadata_2025 huggingface dataset:
A Probabilistic Approach for Economic Evaluation of Occupational Health and Safety Interventions: A Case Study of Silica Exposure Reduction Interventions in the Construction Sector
Authors: Mofidi Amirabbas , Tompa Emile , Mortazavi SeyedBagher , Esfahanipour Akbar , Demers Paul A.
Published: January 2020

Background: Construction workers are at a high risk of exposure to various types of hazardous substances such as crystalline silica. Though multiple studies indicate the evidence regarding the effectiveness of different silica exposure reduction interventions in the construction sector, the decisions for selecting a specific silica exposure reduction intervention are best informed by an economic evaluation. Economic evaluation of interventions is subjected to uncertainties in practice, mostly due to the lack of precise data on important variables. In this study, we aim to identify the most cost-beneficial silica exposure reduction intervention for the construction sector under uncertain situation. Methods: We apply a probabilistic modeling approach that covers a large number of variables relevant to the cost of lung cancer, as well as the costs of silica exposure reduction interventions. To estimate the societal lifetime cost of lung cancer, we use an incidence cost approach. To estimate the net benefit of each intervention, we compare the expected cost of lung cancer cases averted, with expected cost of implementation of the intervention in one calendar year. Sensitivity analysis is used to quantify how different variables effects interventions net benefit. Results: A positive net benefit is expected for all considered interventions. The highest number of lung cancer cases are averted by combined use of wet method, local exhaust ventilation and personal protective equipment, about 107 cases, with expected net benefit of $45.9 million. Results also suggest that the level of exposure is an important determinant for the selection of the most cost-beneficial intervention. Conclusions: This study provides important insights for decision makers about silica exposure reduction interventions in the construction sector. It also provides an overview of the potential advantages of using probabilistic modeling approach to undertake economic evaluations, particularly when researchers are confronted with a large number of uncertain variables.
Genome-wide analysis of long non-coding RNAs (lncRNAs) in two contrasting rapeseed (Brassica napus L.) genotypes subjected to drought stress and re-watering
Authors: Tan Xiaoyu , Li Su , Hu Liyong , Zhang Chunlei
Published: January 2020

Background: Drought stress is a major abiotic factor that affects rapeseed ( Brassica napus L.) productivity. Though previous studies indicated that long non-coding RNAs (lncRNAs) play a key role in response to drought stress, a scheme for genome-wide identification and characterization of lncRNAs’ response to drought stress is still lacking, especially in the case of B . napus . In order to further understand the molecular mechanism of the response of B . napus to drought stress, we compared changes in the transcriptome between Q2 (a drought-tolerant genotype) and Qinyou8 (a drought-sensitive genotype) in response to drought stress and rehydration treatment at the seedling stage.

Results: A total of 5,546 down-regulated and 6,997 up-regulated mRNAs were detected in Q2 compared with 7,824 and 10,251 in Qinyou8, respectively; 369 down-regulated and 108 up-regulated lncRNAs were detected in Q2 compared with 449 and 257 in Qinyou8, respectively. LncRNA- mRNA interaction network analysis indicated that the co-expression network of Q2 was composed of 145 network nodes and 5,175 connections, while the co-expression network of Qinyou8 was composed of 305 network nodes and 22,327 connections. We further identified 34 TFs corresponding to 126 differentially expressed lncRNAs in Q2, and 45 TFs corresponding to 359 differentially expressed lncRNAs in Qinyou8. Differential expression analysis of lncRNAs indicated that up- and down-regulated mRNAs co-expressed with lncRNAs participated in different metabolic pathways and were involved in different regulatory mechanisms in the two genotypes . Notably, some lncRNAs were co-expressed with BnaC07g44670D, which are associated with plant hormone signal transduction. Additionally, some mRNAs which were co-located with XLOC_052298, XLOC_094954 and XLOC_012868 were mainly categorized as signal transport and defense/stress response.

Conclusions: The results of this study increased our understanding of expression characterization of rapeseed lncRNAs in response to drought stress and re-watering, which would be useful to provide a reference for the further study of the function and action mechanisms of lncRNAs under drought stress and re-watering.
Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries
Authors: Osborn Jennifer , Roberts Teri , Guillen Ethan , Bernal Oscar , Roddy Paul , Ongarello Stefano , Sprecher Armand , Page Anne-Laure , Ribeiro Isabela , Piriou Erwan , Tamrat Abiy , Tour Roberto de la , Rao V. Bhargavi , Flevaud Laurence , Jensen Tomas , McIver Lachlan , Kelly Cassandra , Dittrich Sabine
Published: January 2020

Background: Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens.

Method: A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated.

Results: The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidal Salmonella , Plasmodium species and Mycobacterium tuberculosis as the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients.

Conclusion: This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, including the actionability, can result in a broadly applicable priority list. This broad utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.
Lapatinib in combination with capecitabine versus continued use of trastuzumab in breast cancer patients with trastuzumab-resistance: a retrospective study of a Chinese population.
Authors: Yang fan , Huang Xiang , Sun Chunxiao , Li Jianbin , Wang Biyun , Yan Min , Jin Feng , Wang Haibo , Zhang Jin , Fu Peifen , Zeng Tianyu , Wang Jian , Li Wei , Li Yongfei , Yang Mengzhu , Li Jun , Wu Hao , Fu Ziyi , Yin Yongmei , jiang zefei
Published: January 2020

Background: The efficacy and safety of lapatinib plus capecitabine (LC or LX) versus trastuzumab plus chemotherapy in patients with HER-positive metastatic breast cancer who are resistant to trastuzumab is unknown.
Methods: We retrospectively analyzed data from breast cancer patients who began treatment with regimens of lapatinib plus capecitabine (LC or LX) or trastuzumab beyond progression (TBP) at eight hospitals between May 2010 and October 2017.
Results: Among 554 patients who had developed resistance to trastuzumab, the median PFS (progression free survival) was 6.77 months in the LX group compared with 5.6 months in the TBP group (hazard ratio 0.804; 95% CI, 0.67 to 0.96; P=0.019). The central nervous system progression rate during treatment was 5.9% in the LX group and 12.5% in the TBP group (P=0.018).
Conclusion: The combination of lapatinib and capecitabine showed a prolonged PFS relative to TBP in patients who had progressed on trastuzumab.
The DELLA Proteins Interact with MYB21 and MYB24 to Regulate Filament Elongation in Arabidopsis
Authors: Huang Huang , Gong Yilong , Liu Bei , Wu Dewei , Zhang Min , Xie Daoxin , Song Susheng
Published: January 2020

Background: Gibberellin (GA) and jasmonate (JA) are two essential phytohormones for filament elongation in Arabidopsis . GA and JA trigger degradation of DELLAs and JASMONATE ZIM-domain (JAZ) proteins through SCF SLY1 and SCF COI1 separately to activate filament elongation . In JA pathway, JAZs interact with MYB21 and MYB24 to control filament elongation. However, little is known how DELLAs regulate filament elongation.
Results: Here we showed that DELLAs interact with MYB21 and MYB24, and that R2R3 domains of MYB21 and MYB24 are responsible for interaction with DELLAs. Furthermore, we demonstrated that DELLA and JAZ proteins coordinately repress the transcriptional function of MYB21 and MYB24 to inhibit filament elongation .
Conclusion: We discovered that DELLAs interact with MYB21 and MYB24, and that DELLAs and JAZs attenuate the transcriptional function of MYB21 and MYB24 to control filament elongation. This study reveals a novel cross-talk mechanism of GA and JA in the regulation of filament elongation in Arabidopsis .
Keywords: Gibberellin, Jasmonate, MYB21, MYB24, Filament elongation
A survey of seasonal and perennial allergic conjunctivitis in children in southwest China: a case-control study
Authors: Gao Xu , Tang Xiaojiao , Xiang Qin
Published: January 2020

Background: Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) were the most usual types of allergic conjunctivitis. House dust mites were the most common sensitization agents for SAC and PAC. This study aimed to explore SAC and PAC risk factors in children. Methods：We recruited 176 children suffering from SAC or PAC and 131 control subjects in southwest China. A questionnaire was provided to all the subjects’ parents. Several eye exams were performed, and all the subjects received the skin prick test (SPT). We analyzed the questionnaire data, the scores of the symptoms/signs and the SPT results. Results: The percentage of children that had ever been breastfed in the case group was lower than in the control group (P<0.05). The rate of parental allergy history in the case group was higher than for the control group (P<0.01). Compared with the control group, the case group was more likely to have other systemic allergic diseases (P<0.01). Some children in case group had adenoidal hypertrophy (ATH), and incidence rate was different from control group (P<0.05). The ocular symptoms and signs scores had significant correlation to the clinical course (P<0.05), but there was no correlation to the SPT results (P>0.05). Conclusion: Allergic conjunctivitis may coexist with a variety of allergic diseases, and SAC and PAC may be a risk factor for ATH. Breastfeeding should be recommended, as it may be an alleviating factor for allergic diseases, especially for children of parents with a history of allergic diseases. The disease severity is closely related to its course. Therefore, to avoid difficulty in treatment caused by the aggravation of symptoms and signs, timely antiallergic treatment was recommended.
Clinical characteristics and blood/serum bound prognostic biomarkers in advanced pancreatic cancer treated with gemcitabine and nab-paclitaxel
Authors: Blomstrand Hakon , Green Henrik , Fredriksson Mats , Gränsmark Emma , Björnsson Bergthor , Elander Nils
Published: January 2020

Background In recent years treatment options for advanced pancreatic cancer has markedly improved, and a combination regimen of gemcitabine and nab-paclitaxel is now considered standard of care in Sweden and elsewhere. Nevertheless, a majority of patients do not respond to treatment. In order to guide the individual patient to the most beneficial therapeutic strategy, simple and easily available prognostic and predictive markers are needed. Methods The potential prognostic value of a range of blood/serum parameters, patient-, and tumour characteristics was explored in a retrospective cohort of 75 patients treated with gemcitabine/nab-paclitaxel (Gem/NabP) for advanced pancreatic ductal adenocarcinoma (PDA) in the South Eastern Region of Sweden. Primary outcome was overall survival while progression free survival was the key secondary outcome. Result Univariable Cox regression analysis revealed that high baseline serum albumin (> 37 g/L) and high age (>65) were positive prognostic markers for OS, and in multivariable regression analysis both parameters were confirmed to be independent prognostic variables (HR 0.48, p =0.023 and HR=0.47, p =0.039,). Thrombocytopenia at any time during the treatment was an independent predictor for improved progression free survival (PFS) but not for OS (HR 0.49, p =0.029 and 0.54, p =0.073), whereas thrombocytopenia developed under cycle 1 was neither related with OS nor PFS (HR 0.87 p =0.384 and HR 1.04, p =0.771). Other parameters assessed (gender, tumour stage, ECOG performance status, myelosuppression, baseline serum CA19-9, and baseline serum bilirubin levels) were not significantly associated with survival. Conclusion Serum albumin at baseline is a prognostic factor with palliative Gem/NabP in advanced PDA, and should be further assessed as a tool for risk stratification. High age was associated with improved survival, which encourages further studies on the use of Gem/NabP in the elderly.
Incidence, Clinical Profile, and Risk Factors for Serious Bacterial Infections in Children Hospitalized With Fever in Ujjain, India
Authors: Pathak Ashish , Upadhayay Radika , Mathur Aditya , Rathi Sunil , Lundborg Cecilia Stålsby
Published: January 2020

Background
Fever is a cause for concern for both parents and the treating pediatrician and a common reason for antibiotic overuse. However, the proportion of children hospitalized for fever with serious bacterial infection (SBI) is uncertain. We aimed to evaluate the epidemiological, clinical, hematological, and biochemical risks for SBI among the children admitted with fever.
Method
This prospective study was conducted in a rural teaching hospital in India on consecutive children, aged 3 months–12 years, presenting with fever 100°F (37.7°C) or higher. The presence of SBI was confirmed with one of the following criteria: (a) a positive blood culture; (b) roentgenographically confirmed pneumonia with high titres of C-reactive protein; (c) a culture-confirmed urinary tract infection; (d) enteric fever diagnosed clinically in addition to either a positive blood culture or high Widal titers; and (e) meningitis diagnosed clinically in addition to either a positive blood culture or cerebrospinal fluid culture. A predefined questionnaire was filled.
Results
A total of 302 children were included in the study, out of which 47% (95% CI 41.4%-52.7%) presented with SBI. The factors associated with confirmed SBI in bivariate analysis were history of previous hospitalization, history of chronic illness, history of medication in the previous one week, a partially immunized child, history of common cold, moderate-grade fever, toxic look, significant lymphadenopathy, absence of BCG scar, delayed development, irritability, breathlessness, respiratory distress, poor feeding, significant weight loss, suspected urinary tract infection, hyponatremia, hypokalemia, and abnormal leucocyte count. The final generalized logistic regression model revealed partially immunized child (RR 4.26), breathlessness (RR 1.80), weight loss (RR 2.28), and suspected urinary tract infection (RR 1.95) as risk factors for the increased risk of SBI.
Conclusion
The study identified multiple risk factors for SBI. Pediatricians can be made aware of these risk factors. Further studies are warranted to identify age-specific risk factors for SBI because most clinicians depend on clinical signs and symptoms to identify SBI.
Secular trends in testosterone- findings from a large state-mandate care provider
Authors: Chodick Gabriel , Epstein Shdema , Shalev Varda
Published: January 2020

Background: Several studies from the US and Europe have shown a population-level decline in serum testosterone in men from 1970's to early 2000's. However, to the best of our knowledge, no study examining population-level decline in testosterone has been published in more recent years. The study objective was therefore to examine secular trends in testosterone levels among Israeli men in the first and second decades of the 21st century, Methods: All incident total testosterone performed between1/2006 and 3/2019 among 102,334 male members of a large health organization. Results: A significant (p<0.001) and prominent trend of age-independent decline in the testosterone levels was recorded during the study period for most age groups. Conclusions: There was a highly significant age-independent decline in total testosterone in the first and second decades of the 21st century. The decline was unlikely to be explained by increasing rates of obesity.
A novel signature based on m6A related genes as the potential prognostic factor in hepatocellular carcinoma.
Authors: Mo Zhuomao , Luo Shaoju , Hu Hao , Yu Ling , Cao Zhirui , zhang shijun
Published: January 2020

Background Many different signatures and models have been established for patients with hepatocellular carcinoma (HCC), but no signature based on m6A related genes was developed. The objective of this research was to establish the signature with m6A related genes in HCC. Methods Data from 377 HCC patients from The Cancer Genome Atlas (TCGA) database was downloaded. The included m6A related genes were selected by Cox regression analysis and the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Furthermore, the nomogram was constructed and evaluated by C-index, calibration plot and ROC curve. Results The signature was established with the four m6A related genes (YTHDF2, YTHDF1, METTL3 and KIAA1429). Under the grouping from signature, patients in high risk group of showed the poor prognosis than those in low risk group. And significant difference was found in two kinds of immune cells (T cell gamma delta and NK cells activated) between two groups. The univariate and multivariate Cox regression analysis indicated that m6A related signature can be the potential independent prognosis factor in HCC. Finally, we developed a clinical risk model predicting the HCC prognosis and successfully verified it in C-index, calibration and ROC curve. Conclusion Our study identified the m6A related signature for predicting prognosis of HCC and provided the potential biomarker between m6A and immune therapy.
Healing Pattern of Thoracolumbar Burst Fracture after Posterior Short-segmental Fixation
Authors: Liang Changxiang , Liu Guihua , Liang Guoyan , Zheng Xiaoqing , Yin Dong , Xiao Dan , Zeng Shixing , Cai Honghua , Chang Yunbing
Published: January 2020

Background: Vertebral cavity sometimes occurs after posterior short-segmental fixation for thoracolumbar burst fractures, but the risk factor of its formation is unclear. We aim to investigate their vertebral healing pattern and explore the risk factor of vertebral cavities.Methods: The thoracolumbar burst fractured patient treated with posterior short segmental fixation were followed up for minimal 3 years. Healing patterns were observed and divided into 4 healing types according to the integrity status of the endplates and the morphology of the cavities. The demographic characteristics and clinical outcomes were compared between patients with and without vertebra cavities at the last follow-up.Results: The incidence of vertebral cavities in our cohort was 59.6%. Accordingly, the healing pattern of the vertebra were classified as Complete Healing type or Endplate Cavity type, Spherical Cavity type or Burst Cavity type. The proportion of men, history of smoking, severity of neurological impairment and presence of A4 type fracture were significantly higher in the Vertebral Cavity group than the Intact Vertebra group. Clinical outcomes, including ASIA scales,VAS and ODI scores, were similar between the Intact Vertebra group and the Vertebral Cavity group. Conclusions: Vertebral cavities are commonly seen after posterior short-segmental fixation for thoracolumbar burst fractures. The healing pattern can be divided into four types. The presence of vertebral cavity may be related to gender, smoking history and the severity of the fracture. Most of the vertebral cavities are asymptomatic, but the clinical significance needs further study.
Complications and Hospital Stay after Endoscopic Retrieval of Drug Baggies in Body Stuffers: An Observational Prospective Study
Authors: Shabani Mahtab , Kefayati Marzieh , Hassanian-Moghaddam Hossein , Zamani Nasim , McDonald Rebecca
Published: January 2020

Background Body stuffers routinely receive conservative treatment, i.e. administration of the laxative polyethylene glycol for the passage of ingested drug baggies and observation. Endoscopic baggie removal may offer a safe alternative that could result in shorter hospitalization. We aimed to compare complications, hospital stay, and final outcome in body stuffers assigned to endoscopy versus conservative treatment. Methods This is an observational prospective study of body stuffers presenting to a clinical toxicology center in Tehran (Iran) in 2016-2019, irrespective of the drug ingested. Eligible patients had baggies in their upper gastrointestinal tract and presented without severe poisoning. Patients received either endoscopy or conservative treatment, and clinical outcomes were compared between the groups. Results A total of 69 patients were enrolled, with a median age of 29 years (range: 18–64), among whom 1 was female (2%). Eighteen and 51 patients were endoscopically and conservatively managed, respectively. Drugs most commonly ingested were heroin in endoscopy patients (8/18 cases; 44%) and methamphetamine in the conservative group (28/51 cases; 55%). Endoscopy patients had a shorter hospital stay (median 1.5 vs. 2 days, p = 0.018). In the conservative group, one patient died, and the rate of complications was significantly higher, with more patients experiencing side effects (OR= 1.4, 95% CI = 1.2, 1.7) and requiring intubation (OR = 1.3, 95% CI = 1.1, 1.5). Conclusion Endoscopic retrieval was associated with fewer complications and shorter hospitalization. Endoscopy may be a safe treatment for body stuffers without severe toxicity on presentation.
Identification of stress repressive zinc finger gene family and its expression analysis in rice under abiotic constraints
Authors: Zhang Chao , Tan Yanning , Essemine Jemaa , Li Ni , Hu Zhongxiao , Liu Hai , Xu Qiusheng , Qu Mingnan , Fang Baohua , Wang Weiping
Published: January 2020

Background: Stress repressive zinc finger (SRZ) gene family in rice is one of the plant defense gene families that play a pivotal role in plant growth regulation and development, particularly under stressful conditions. However, there is no genome-wide survey regarding SRZ gene family in rice (OsSRZ) till date. Results: We studied, herein, this gene family by performing a genome-wide screening and we identified 25 OsSRZ gene members using Japonica cultivar as an investigating material. Their chromosome localizations, phylogenetic relationships, genomic structures, conserved domains and promoter cis-regulatory elements were analyzed. Besides, their spatio-temporal expression profiles and expression patterns under various hormones and stress treatments were also assessed. Based on the phylogeny and domain constitution, the OsSRZ gene family was classified into five groups (I-V). Conserved domains analysis demonstrates that OsSRZ proteins contain at least one highly conserved SRZ domain. The analysis of expression patterns of the SRZ gene family reveal that OsSRZ genes display tissue-specific expression patterns at various rice developmental stages and exhibit differential responses to both phytohormones and abiotic stresses. Furthermore, q-RT-PCR analysis reveals that Os SRZ genes exhibit different expression patterns under various abiotic stresses. We notice the presence of a single specific gene considerably or strongly up-regulated for each kind of abiotic stress. Over 12 OsSRZ genes analyzed with q-RT-PCR, solely 4 genes (OsSRZ 1, 2, 10 and 11) were found to be substantially or strongly up-regulated following abiotic stress. Notably, OsSRZ 10 and 11 were up-regulated under heat stress by 7 and 5 times, respectively. However, OsSRZ2 was up-regulated by 7 and 3.5 folds under salt and cold stresses, respectively. Interestingly, OsSRZ1 was up-regulated by about 3~11 times in 24 h following artificial oxidative stress application using 1 mM H2O2 . Conclusions: We deduce that some members of OsSRZ gene family function as abiotic stress marker in rice. At the genomic level and expression pattern, our genome-wide survey could provide promising and valuable insights to widen and strengthen further future investigation by leading a cutting edge research regarding the biological and molecular functions of this gene family.
Versatile physiological functions of the Nudix Hydrolase family in berry development and stress response in grapevine
Authors: Wang Zhaoke , Wang Peipei , Guan Le , Haider Muhammad Salman , Nasim Maazullah , Fang Jinggui , Liu Gengsen , Leng Xiangpeng
Published: January 2020

Background Nudix hydrolases are widely distributed across all classes of organisms and provide the potential capacity to hydrolyze a wide range of organic pyrophosphates. Although Nudix hydrolases are involved in plants detoxification processes in response to abiotic and biotic stresses, the biological functions of Nudix hydrolases remain largely unclear in grapevine. Results A total of 25 putative grapevine Nudix hydrolases ( VvNUDXs ) were identified by bioinformatics analysis and classified into eight subfamilies based to their preferred substrates. Both tandem and segmental duplications were responsible for the evolution and expansion of NUDX gene family in grapevine. To investigate into their regulatory roles of VvNUDX genes during growth and development as well as in response to abiotic and biotic stress in grapevine, the expression patterns were revealed in publicly available microarray data. The spatial and temporal expression patterns of VvNUDX genes indicated that these genes might play important roles in multiple developmental processes. Transcriptome and qRT-PCR analysis exhibited that ten VvNUDX genes were specifically expressed in grapevine berries, suggesting the potential roles in grapevine berry development. Expression and phylogenetic analysis demonstrated that VvNUDX1 and VvNUDX3 might be involved in terpenoid biosynthesis in grapevine. Futhermore, most VvNUDX genes toward the ADP-ribose/NADH were different patterns in response to various abiotic and biotic stresses, such as salinity and drought, as well as different types of biotic treatments, such as Erysiphe necator , Bois Noir phytoplasma and leaf-roll-associated virus-3 (GLRaV-3). Conclusions These results showed that VvNUDX were associated with plant detoxification processes in response to abiotic and biotic stresses, and regulate disease immunity and resistance pathways. The present informations may provide good opportunities to explore the physiological functions of VvNUDX genes in berry development and stress response networks in grapevine.
Ameliorating process parameters for zeaxanthin yield in Arthrobacter gandavensis MTCC 25325
Authors: Ram Shristi , Tirkey Sushma Rani , Kumar Madhava Anil , Mishra Sandhya
Published: January 2020

The present study aims to screen potential bacterial isolates for the production of a prophylactic agent zeaxanthin; which is considered to be an inevitable inclusion in human diet. A freshwater bacterium Arthrobacter gandavensis was isolated from Bor Talav, Bhavnagar and screened as a promising producer of zeaxanthin. The chemo-metric tools were employed to optimize the influencing factors such as pH, temperature, inoculum size, agitation speed, carbon source and harvest time on its yield. Thereafter, 6 parameters were narrowed down to 3 factors and were optimized using the central composite design (CCD) matrix. Maximum zeaxanthin (1.51 mg/g) was derived when A. gandavensis was grown under pH 6.0, 1.5% (w/v) glucose and 10% (v/v) inoculum size. A high regression coefficient ( R 2 =0.92) of the developed model indicated the accurateness with the tested parameters. To the best of our knowledge, this is the first report on tailoring of process parameters using chemo-metric optimization for escalating the zeaxanthin production by A. gandavensis.
Bloodstream Infections caused by Klebsiella pneumoniae and Serratia marcescens isolates co-harboring NDM-1 and KPC-2.
Authors: Bes Taniela , Nagano Debora , Martins Roberta , Marchi Ana Paula , Neto Lauro Perdigão , Higashino Hermes , Prado Gladys , Guimaraes Thais , Levin Anna S , Costa Silvia
Published: January 2020

Carbapenem-resistant Enterobacteriaceae is a worldwide health problem, however isolates carrying both blaKPC-2 and blaNDM-1 are unusual. Here we describe microbiological and clinical characteristics of five cases of bloodstream infection (BSI) caused by carbapenem-resistant K lebsiella pneumoniae and Serratia marcescens co-harboring blaKPC-2 and blaNDM-1.Of the five blood culture isolates, three from are from hematopoietic stem cell transplantation patients, one from a renal transplant patient, and one from a soft tissue surgical patient. All patients lived in low-income neighborhoods and had no travel history. Despite antibiotic treatment, four of five patients died. The phenotypic assays showed that Meropenem added with either EDTA, PA or both showed increased zone of inhibition in comparison to Meropenem alone. Molecular tests confirmed blaKPC-2 and blaNDM-1 genes, the K. pneumoniae were assigned as ST258 and ST340 by Whole Genome Sequencing.
Apgar Score and Umbilical Cord pH as Prognostic Predictors in Very Low Birth Weight Premature Neonates
Authors: Barzilay Bernard , Ratner Miri , Bibi Haim , Abu-Kishk Ibrahim
Published: January 2020

Objective To estimate the reliability of the Apgar score (AS) and umbilical cord pH (UCP) as prognostic tools among very low birth weight (VLBW) infants. Study Design Retrospective study based on data of 1237 VLBW neonates born between 1997 and 2013 at one tertiary medical center. For each newborn, a complication score (CS) was calculated based on common complications of prematurity. Results The AS at 1 and 5 minutes correlated well with CS (correlation coefficients -0.47 and -0.52, respectively). No significant correlation was found between UCP and CS (correlation coefficient -0.08). Multi regression analysis revealed that the variables with the greatest prognostic contribution were birth weight, gestational age and prenatal steroid administration (beta values 0.277, 0.251 and 0.087, respectively). Conclusion The AS at 1 and 5 minutes, but not UCP, combined with gestational age, birth weight, and prenatal steroids, can be significant parameters for predicting prognosis among VLBW neonates.
Opening Large-Conductance Potassium Channels Selectively Induced Cell Death of Triple-Negative Breast Cancer
Authors: Sizemore Gina , McLaughlin Sarah , Newman Mackenzie , Brundage Kathleen , Ammer Amanda , Martin Karen , Pugacheva Elena , Coad James , Mattes Malcolm , Yu Han-Gang
Published: January 2020

Background: Unlike other breast cancer subtypes that may be treated with a variety of hormonal or targeted therapies, there is a need to identify new, effective targets for triple-negative breast cancer (TNBC). It has recently been recognized that membrane potential is depolarized in breast cancer cells. The primary objective of the study is to explore whether hyperpolarization induced by opening potassium channels may provide a new strategy for treatment of TNBC.
Methods: Breast cancer datasets in cBioPortal for cancer genomics was used to search for ion channel gene expression. Immunoblots and immunohistochemistry were used for protein expression in culture cells and in the patient tissues. Electrophysiological patch clamp techniques were used to study properties of BK channels in culture cells. Flow cytometry and fluorescence microscope were used for cell viability and cell cycle studies. Ultrasound imaging was used to study xenograft in female NSG mice.
Results: In large datasets of breast cancer patients, we identified a gene, KCNMA1 (encoding for a voltage- and calcium-dependent large-conductance potassium channel, called BK channel), overexpressed in triple-negative breast cancer patients. Although overexpressed, 99% of channels are closed in TNBC cells. Opening BK channels hyperpolarized membrane potential, which induced cell cycle arrest in G2 phase and apoptosis via caspase-3 activation. In a TNBC cell induced xenograft model, treatment with a BK channel opener significantly slowed tumor growth without cardiac toxicity.
Conclusions: Our results support the idea that hyperpolarization induced by opening BK channel in TNBC cells can become a new strategy for development of a targeted therapy in TNBC.
Prevalence and risk factors for adult cataract in the Jingan district of Shanghai
Authors: Sun Yang , Ye Xiaofang , Lu Yi , Xu Jianjiang , Xu Jianming , Ji Yinghong
Published: January 2020

BackgroundTo report the prevalence of age-related cataract (ARC) in the Jingan district of Shanghai and analyze the risk factors for ARC.MethodsDuring March to June in 2010, a cross sectional study was conducted in a community selected by stratified cluster sampling in the Jingan district of Shanghai. Residents aged 40 and older were recruited and investigated by questionnaire and ophthalmic examination.ResultsA total of 2894 subjects aged 40 years and above were included in our study. 948 people (32.8%) were diagnosed with cataract including 845 with bilateral cataract and 292 with moderate and severe visual impairment (low vision). There were significant differences in the risk of cataract among different age groups and genders. The multivariable Logistic analysis suggested that the prevalence of cataract increased with age. Persons at lower risk for ARC were those with higher education status (OR=0.722), with refractive error (OR=1.352), and those who used computers for 3-8 hours every day (OR=0.592).ConclusionAge, refractive error, education level and daily time of using computers have a certain correlation with ARC.
Molecular epidemiology and antimicrobial resistance of group A streptococcus recovered from patients in Children
Authors: Li Hongxin , Zhou Lin , Zhao Yong , Ma Lijuan , Liu Xiaoyan , Hu Jin
Published: January 2020

Background: Group A streptococcus (GAS) is an important human pathogen responsible for a broad range of infections. Epidemiological surveillance has been crucial to detect changes in the geographical and temporal variation of the disease pattern. The objective of this study was to investigate the molecular epidemiological characteristics and antimicrobial resistance of GAS isolates from patients in Children’s Hospital in Beijing.Methods: From 2016 to 2017, pharyngeal swab samples were collected from the outpatients in Children’s Hospital, Capital Institute of Pediatrics, who were diagnosed as scarlet fever. Antimicrobial susceptibility test was performed according to the distribution of common antibiotics and Clinical and Laboratory Standards Institute (CLSI) recommendations. The distribution of the macrolide-resistance genes ( ermB, ermA, mefA ), emm (M protein-coding gene) typing, and superantigens (SAg) gene profiling were examined by polymerase chain reaction (PCR).Results: A total of 297 GAS strains were collected. The sensitivity of the strains to penicillin, ceftriaxone, and levofloxacin was 100%. The rate of antimicrobial resistance to erythromycin and clindamycin were 98.3% and 96.6%, respectively. The dominant emm types were emm12 (65.32%), emm1 (27.61%), emm75 (2.69%), and emm89 (1.35%). Of the 297 isolates, 290 (97.64%) carried the ermB gene, and 5 (1.68%) carried the mefA gene, while none carried the ermA gene. The most common superantigen genes identified from GAS isolates were smeZ (96.97%) , speC (92.59%), speG (91.58%), and ssa (85.52%), speI (54.55%), speH (52.19%), and speA (34.34%). Isolates with the genotype emm 1 possessed speA, speC, speG, speJ, speM, ssa, and smeZ, while emm 12 possessed speC, speG, speH, speI, speM, ssa, and smeZ superantigens. Conclusions: The prevalent strain of GAS isolates in Beijing has a high antimicrobial resistance rate to macrolides, while penicillin can still be used as the preferred treatment choice. The primary mechanism of resistance to erythromycin is related to the expression of ermB . The common emm types were e mm 12 and emm 1. A correlation was established between emm and the superantigen gene. Thus, long-term monitoring and investigation of the emm types and superantigen genes of GAS prevalence is imperative.
Quality Of Post-Abortion Care In Java, Indonesia: An Essential Services Analysis ﻿
Authors: Philbin Jesse , Soeharno Nugroho , Giorgio Margaret , Kurniawan Rico , Ingerick Meghan , Utomo Budi
Published: January 2020

Background High maternal mortality in Indonesia persists despite economic growth and a reform that extended health insurance to all Indonesians. Quality of obstetric health services, in general, has been identified as a factor for this; in addition, the country’s restrictive abortion laws merit special attention to the quality of post-abortion care (PAC) services. Methods Using data from a survey of 657 hospitals and emergency obstetric-registered public health centers in Java, Indonesia’s most populous island, we used the essential services framework to measure the health system’s capacity to offer PAC. We then used this framework to explore how Java’s capacity to offer PAC could change given two hypothetical reforms. Finally, we calculated the proportion of PAC patients treated using each of four different procedures. Results No emergency obstetric health centers (PONEDs) are adequately staffed or authorized to offer basic PAC services, while 46% of all hospitals in Java have the full set of services needed. These proportions increase in hypothetical scenarios in which PAC authorization is expanded to midwives, general physicians, and PONED facilities. Eighty-eight percent of PAC patients were treated using dilation and curettage (D&C). Conclusions Allowing clinicians other than Ob/Gyns to perform uterine evacuation and offering first-trimester PAC service in PONEDs would greatly improve the capacity of Java’s health system to serve PAC patients. Increasing the use of vacuum aspiration and misoprostol would lower the burden of treatment for patients, reduce costs to the health system, and facilitate the task-shifting efforts needed to expand access to this life-saving service.
The intention on Modern Contraceptive Use and Associated Factors among Postpartum Women in Public health institutions of Sodo Town, Southern Ethiopia 2019: Institutional Based Cross-Sectional Study.
Authors: Gebeyehu Natnael Atnafu , Abebe Kelemu
Published: January 2020

Background: The postpartum period is an important transitional time for couples to put the decision on family planning utilization. However, women in Ethiopia are usually uncertain about the use of family planning during this period. This study was aimed to assess the intention of modern contraceptive use and associated factors among postpartum women attending the immunization clinic in Sodo Town.Method: Institutional based cross-sectional study design with a sample size of 416 was conducted from May 25 to June 20, 2019. The data were collected by using a systematic random sampling technique of interviewer-administered questionnaires. Those candidate variables at Bivariate analysis with a p-value<0.2 were moved to the Multivariate logistic regression model to control potential confounding variables and P-value<0.05 at multivariate analysis was considered as a cutoff pointResults: A total of 416 postpartum women participated in the study yielding a response rate of 98.1 % and 291 (70%) of them had an intention on modern contraceptive use. The odds of intention on modern contraceptive use was higher among respondents who had secondary school education (AOR=2.052, 95%CI: 1.064-3.958) than participants with no formal education. It was also higher among antenatal care visit attendees (AOR=1.736,95%CI:1.021-2.951) than those did not attend antenatal care visit. Knowledgeable participants on modern contraceptive use were more likely intend to use (AOR=2.535, 95%CI: 1.499-4.282) than their counterparts. Besides, the odds of the intention of modern contraceptive use among postpartum women who had menses resumption were higher (AOR=2.047,95%CI:1.141-3.675)than those whose menses not resumed.Participants who had husband approval were more likely to intend to use contraceptives (AOR=2.395,95%CI:1.501-5.458) than their counterparts.Conclusion: The intention of modern contraceptives among postpartum women was low. Family planning providers should emphasize reducing barriers of intention like lack of education, knowledge, male partner approval, antenatal care visit and advise the impact of menses on fertility.
Predictors of the use of analgesic drugs 1 year after joint replacement: a single-center analysis of 13,000 hip and knee replacements
Authors: Rajamäki Tuomas , Puolakka Pia A. , Hietaharju Aki , Moilanen Teemu , Jämsen Esa
Published: January 2020

Background: Pain persists in a moderate number of patients following hip or knee replacement surgery. Persistent pain may subsequently lead to the prolonged consumption of analgesics after surgery and expose patients to the adverse drug events of opioids and NSAIDs, especially in older patients and patients with comorbidities. This study aimed to identify risk factors for the increased use of opioids and other analgesics one year after surgery and focused on comorbidities and surgery-related factors.Methods: All patients who underwent a primary hip or knee replacement for osteoarthritis from 2002 to 2013 were identified. Redeemed prescriptions for acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids (mild and strong) were collected from a nationwide Drug Prescription Register. The user rates of analgesics and the adjusted odds ratios for analgesic use one year after joint replacement were calculated.Results: Of the 6,238 hip replacement and 7,501 knee replacement recipients, 3,591 (26.1%) were still using analgesics one year after surgery. Significant predictors of overall analgesic use (acetaminophen, NSAID, or opioid) were (odds ratio (95% CI)) age 65-74.9 years (reference <65), 1.2 (1.04-1.3), age > 75 years, 1.3 (1.2-1.5), female gender, 1.3 (1.2-1.4), BMI 30-34.9 kg/m2 (reference <25kg/m2), 1.2 (1.03-1.5), BMI >35 kg/m2, 1.7 (1.4-2.2), a higher number of comorbidities (according to modified Charlson Comorbidity Index score), 1.4 (1.2-1.6), and hypertension, 1.1 [1.00–1.2]. Diabetes and other comorbidities were not significant independent predictors. Of the other clinical factors, the preoperative use of analgesics, 4.0 (3.6-4.3) and knee surgery, 1.3 (1.2-1.4), predicted the use of analgesics, whereas simultaneous bilateral knee replacement (compared to unilateral procedure) was a protective factor, 0.80 (0.70-0.92). Opioid use was associated with obesity, higher CCI score, epilepsy, knee vs hip surgery, unilateral vs bilateral knee operation, total vs unicompartmental knee replacement, and the preoperative use of analgesics/opioids.Conclusions: Obesity (especially BMI >35 kg/m2) and the preoperative use of analgesics were the strongest predictors of an increased postoperative use of analgesics. It is remarkable that also older age and higher number of comorbidities predicted analgesic use despite these patients being the most vulnerable to adverse drug events.
Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis -The ANSWER cohort study-
Authors: Ebina Kosuke , Hirano Toru , Maeda Yuichi , Yamamoto Wataru , Hashimoto Motomu , Murata Koichi , Takeuchi Tohru , Shiba Hideyuki , Son Yonsu , Amuro Hideki , Onishi Akira , Akashi Kengo , Hara Ryota , Katayama Masaki , Yamamoto Keiichi , Kumanogoh Atsushi , Hirao Makoto
Published: January 2020

Background: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA).Methods: This study assessed 3,897 patients and 4,415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2,737 bDMARDs-naïve patients and 1,678 bDMARDs-switched patients [59.5% switched to their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [42.4%], and methotrexate [MTX] dose 8.5 mg/week [60.9%]). Treatment courses included abatacept (ABT; n=663), adalimumab (ADA; n=536), certolizumab pegol (CZP; n=226), etanercept (ETN; n=856), golimumab (GLM; n=458), infliximab (IFX; n=724), tocilizumab (TCZ; n=851), and TOF (n=101/only bDMARDs-switched cases). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX, starting date, and number of switched bDMARDs) using Cox proportional hazards modeling.Results: Adjusted drug retention rates for each discontinuation reason were as follows: lack of effectiveness in the bDMARDs-naïve group (from 70.8% [CZP] to 85.1% [ABT]; P=0.001 between agents) and the bDMARDs-switched group (from 52.8% [CZP] to 78.7% [TCZ]; P<0.001 between agents). Toxic adverse events in the bDMARDs-naïve group (from 86.9% [IFX] to 96.3% [ABT]; P<0.001 between agents) and the bDMARDs-switched group (from 81.1% [ADA] to 95.4% [ETN]; P=0.01 between agents). Finally, overall retention rates excluding discontinuation for non-toxic reasons or remission ranged from 64.2% (IFX) to 82.0% (ABT) (P<0.001 between agents) in the bDMARDs-naïve group and from 44.2% (ADA) to 66.8% (TCZ) (P<0.001 between agents) in the bDMARDs-switched group. Conclusions: Remarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.