bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of economic burden and its associated factors of twenty-three rare diseases in Shanghai
Authors: Cai Xiaoshu , Yang Hui , Genchev Georgi Z. , Lu Hui , Yu Guangjun 
Published: October 2019

AbstractBackgroundIt is estimated that at present there are over 10 million rare disease patients in China. Recently an increased focus from policy perspective has been placed on rare diseases management. Improved disease definitions and the releases of local and national rare disease lists are some of the steps taken already. Despite these developments, few Chinese rare disease-related epidemiology and economic studies exist, thus hindering assessment of the true burden of rare diseases. For a rare disease with an effective treatment, this is a particularly important aspect due to the often-high cost associated.ObjectiveThe goal of this study is to address the data scarcity on the subject of rare diseases economic impact in China. We aim to address an existing knowledge gap and to provide a timely analysis of the economic burden of 23 rare diseases in Shanghai, China.MethodsWe utilized the data from the Health Information Exchange system of Shanghai and employed statistical modeling to analyze the economic burden of rare diseases with an effective treatment in Shanghai.ResultsFirst, we described the actual direct medical expenditure and analyzed its associated factors. Second, we found age, disease type, number of complications, and payment type were significantly associated with rare disease medical direct costs. Third, a generalized linear model was employed to estimate the annual direct cost. The mean direct medical cost was estimated as ¥9588 (US$1521) for inpatients and ¥1060 (US$168) for outpatients, and was over ¥15 million (~US$2.4 million) per year overall.ConclusionOur study is one of the first quantifying the economic burden of an extensive set of rare diseases in Shanghai and China. Our results can serve to inform healthcare-focused policy making, contribute to the increase of public awareness, and incentivize development of rare-disease strategies and treatments specific to the Chinese context.
Unsuccessful intravenous D-mannose treatment in PMM2-CDG
Authors: Grünert Sarah C. , Marquardt Thorsten , Lausch Ekkehart , Fuchs Hans , Thiel Christian , Sutter Martin , Schumann Anke , Hannibal Luciana , Spiekerkoetter Ute 
Published: October 2019

Abstract

Background
PMM2-CDG (Phosphomannomutase 2 - Congenital disorder of glycosylation-Ia; CDG-Ia) is the most common glycosylation defect, often presenting as a severe multisystem disorder that can be fatal within the first years of life. While mannose treatment has been shown to correct glycosylation in vitro and in vivo in mice, no convincing effects have been observed in short-term treatment trials in single patients so far.

Results
We report on a boy with a severe PMM2-CDG who received a continuous intravenous mannose infusion over a period of 5 months during the first year of life in a dose of 0.8 g/kg/day. N-glycosylation of serum glycoproteins and mannose concentrations in serum were studied regularly. Unfortunately, no biochemical or clinical improvement was observed, and the therapy was terminated at age 9 months.

Conclusion
Postnatal intravenous D-mannose treatment seems to be ineffective in PMM2-CDG.
Current concepts of perioperative monitoring in high-risk surgical patients: a review
Authors: Aseni Paolo , Orsenigo Stefano , Storti Enrico , Pulici Marco , Arlati Sergio 
Published: October 2019

Abstract
A substantial number of patients are at high-risk of intra- or post-operative complications or both. Most perioperative deaths are represented by patients who present insufficient physiological reserve to meet the demands of major surgery. Recognition and management of critical high-risk surgical patients require dedicated and effective teams, capable of preventing, recognize, start treatment with adequate support in time to refer patients to the satisfactory ICU level provision. The main task for health-care planners and managers is to identify and reduce this severe risk and to encourage patient’s safety practices. Inadequate tissue perfusion and decreased cellular oxygenation due to hypovolemia, heart dysfunction, reduced cardiovascular reserve, and concomitant diseases are the most common causes of perioperative complications. Hemodynamic, respiratory and careful sequential monitoring have become essential aspects of the clinical practice both for surgeons and intensivists. New monitoring techniques have changed significantly over the past few years and are now able to rapidly identify shock states earlier, define the etiology, and monitor the response to different therapies. Many of these techniques are now minimally invasive or non-invasive. Advanced hemodynamic and respiratory monitoring combines invasive, non-invasive monitoring skills. Non-invasive ultrasound has emerged during the last years as an essential operative and perioperative evaluation tool, and its use is now rapidly growing. Perioperative management guided by appropriate sequential clinical evaluation combined with respiratory and hemodynamic monitoring is an established tool to help clinicians to identify those patients at higher risk in the attempt to reduce the complications rate and potentially improve patient outcomes. This review aims to provide an update of currently available standard concepts and evolving technologies of the various respiratory and hemodynamic monitoring systems for the high-risk surgical patients, highlighting their potential usefulness when integrated with careful clinical evaluation.
Myeloid-derived suppressor cells in hematological malignancies: friends or foes
Authors: Lv Meng , Wang Ke , Huang Xiao-jun 
Published: October 2019

Abstract
Myeloid-derived suppressor cells (MDSCs) are newly identified immature myeloid cells that are characterized by the ability to suppress immune responses and expand during cancer, infection, and inflammatory diseases. Although MDSCs have attracted a lot of attention in the field of tumor immunology in recent years, little is known about their multiple roles in hematological malignancies as opposed to their roles in solid tumors. This review will help researchers better understand the various characteristics and functions of MDSCs, as well as the potential therapeutic applications of MDSCs in hematological malignancies, including lymphoma, multiple myeloma, leukemia, and hematopoietic stem cell transplantation.
A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer
Authors: Wang Jinhua , Xing Yajing , Wang Yingying , He Yundong , Wang Liting , Peng Shihong , Yang Lianfang , Xie Jiuqing , Li Xiaotao , Qiu Wenwei , Yi Zhengfang , Liu Mingyao 
Published: October 2019

Abstract

Background
Cancer-initiating cell (CIC), a functionally homogeneous stem-like cell population, is resonsible for driving the tumor maintenance and metastasis, and is a source of chemotherapy and radiation-therapy resistance within tumors. Targeting CICs self-renewal has been proposed as a therapeutic goal and an effective approach to control tumor growth. BMI-1, a critical regulator of self-renewal in the maintenance of CICs, is identified as a potential target for colorectal cancer therapy.

Methods
Colorectal cancer stem-like cell lines HCT116 and HT29 were used for screening more than 500 synthetic compounds by sulforhodamine B (SRB) cell proliferation assay. The candidate compound was studied in vitro by SRB cell proliferation assay, western blotting, cell colony formation assay, quantitative real-time PCR, flow cytometry analysis, and transwell migration assay. Sphere formation assay and limiting dilution analysis (LDA) were performed for measuring the effect of compound on stemness properties. In vivo subcutaneous tumor growth xenograft model and liver metastasis model were performed to test the efficacy of the compound treatment. Student’s t test was applied for statistical analysis.

Results
We report the development and characterization of a small molecule inhibitor QW24 against BMI-1. QW24 potently down-regulates BMI-1 protein level through autophagy-lysosome degradation pathway without affecting the BMI-1 mRNA level. Moreover, QW24 significantly inhibits the self-renewal of colorectal CICs in stem-like colorectal cancer cell lines, resulting in the abrogation of their proliferation and metastasis. Notably, QW24 significantly suppresses the colorectal tumor growth without obvious toxicity in the subcutaneous xenograft model, as well as decreases the tumor metastasis and increases mice survival in the liver metastasis model. Moreover, QW24 exerts a better efficiency than the previously reported BMI-1 inhibitor PTC-209.

Conclusions
Our preclinical data show that QW24 exerts potent anti-tumor activity by down-regulating BMI-1 and abrogating colorectal CICs self-renewal without obvious toxicity in vivo, suggesting that QW24 could potentially be used as an effective therapeutic agent for clinical colorectal cancer treatment.
Robust taxonomic classification of uncharted microbial sequences and bins with CAT and BAT
Authors: von Meijenfeldt F. A. Bastiaan , Arkhipova Ksenia , Cambuy Diego D. , Coutinho Felipe H. , Dutilh Bas E. 
Published: October 2019

AbstractCurrent-day metagenomics analyses increasingly involve de novo taxonomic classification of long DNA sequences and metagenome-assembled genomes. Here, we show that the conventional best-hit approach often leads to classifications that are too specific, especially when the sequences represent novel deep lineages. We present a classification method that integrates multiple signals to classify sequences (Contig Annotation Tool, CAT) and metagenome-assembled genomes (Bin Annotation Tool, BAT). Classifications are automatically made at low taxonomic ranks if closely related organisms are present in the reference database and at higher ranks otherwise. The result is a high classification precision even for sequences from considerably unknown organisms.
Comparison of cytosine base editors and development of the BEable-GPS database for targeting pathogenic SNVs
Authors: Wang Ying , Gao Runze , Wu Jing , Xiong Yi-Chun , Wei Jia , Zhang Sipin , Yang Bei , Chen Jia , Yang Li 
Published: October 2019

Abstract
A variety of base editors have been developed to achieve C-to-T editing in different genomic contexts. Here, we compare a panel of five base editors on their C-to-T editing efficiencies and product purity at commonly editable sites, including some human pathogenic C-to-T mutations. We further profile the accessibilities of 20 base editors to all possible pathogenic mutations in silico. Finally, we build the BEable-GPS (Base Editable prediction of Global Pathogenic SNVs) database for users to select proper base editors to model or correct disease-related mutations. The in vivo comparison and in silico profiling catalog the availability of base editors and their broad applications in biomedical studies.
Susceptibility to insecticides and resistance mechanisms in three populations of Aedes aegypti from Peru
Authors: Pinto Jesus , Palomino Miriam , Mendoza-Uribe Leonardo , Sinti Carmen , Liebman Kelly A. , Lenhart Audrey 
Published: October 2019

AbstractBackgroundEpidemics of dengue, chikungunya and Zika are a growing threat to areas whereAedes aegyptiare present. The efficacy of chemical control ofAe. aegyptiis threatened by the increasing frequency of insecticide resistance. The objective of this study was to determine the susceptibility status as well as the biochemical and molecular mechanisms underlying insecticide resistance in three populations ofAe. aegyptiin high risk areas of dengue, chikungunya, and Zika in Peru.MethodsBioassays were conducted on adultAe. aegyptito evaluate their susceptibility to insecticides used currently or historically for mosquito control in Peru, including six pyrethroids, three organophosphates and one organochlorine, in populations ofAe. aegyptifrom the districts of Chosica (Department of Lima), Punchana (Department of Loreto) and Piura (Department of Piura). Resistance mechanisms were determined by biochemical assays to assess activity levels of key detoxification enzyme groups (nonspecific esterases, multi-function oxidases, glutathione S-transferases and insensitive acetylcholinesterase). Real-time PCR assays were used to detect twokdrmutations (V1016I and F1534C) on the voltage-gated sodium channel gene.ResultsResistance to DDT was detected in all three populations, and resistance to pyrethroids was detected in all populations except the population from Chosica, which still exhibited susceptibility to deltamethrin. Resistance to organophosphates was also detected, with the exception of populations from Punchana and Piura, which still demonstrated susceptibility to malathion. In general, no increase or alteration of activity of any enzyme group was detected. Both 1016I and 1534C alleles were detected in Punchana and Piura, while only the 1534C allele was detected in Chosica.ConclusionsThe results suggest that resistance to multiple classes of insecticides exist in areas important toAe. aegypti-borne disease transmission in Peru. The F1534C mutation was present in all 3 populations and the V1016I mutation was present in 2 populations. To our knowledge, this is the first report of the presence of 1016I and 1534C inAe. aegyptiin Peru. The absence of highly elevated enzymatic activity suggests that target site resistance is a key mechanism underlying insecticide resistance in these populations, although further research is needed to fully understand the role of metabolic resistance mechanisms in these populations.
Impact of a single round of mass drug administration with azithromycin on active trachoma and ocular Chlamydia trachomatis prevalence and circulating strains in The Gambia and Senegal
Authors: Harding-Esch Emma M. , Holland Martin J. , Schémann Jean-François , Sillah Ansumana , Sarr Boubacar , Christerson Linus , Pickering Harry , Molina-Gonzalez Sandra , Sarr Isatou , Andreasen Aura A. , Jeffries David , Grundy Chris , Mabey David C. W. , Herrmann Bjorn , Bailey Robin L. 
Published: October 2019

Abstract

Background
Mass drug administration (MDA) with azithromycin is a cornerstone of the trachoma elimination strategy. Although the global prevalence of active trachoma has declined considerably, prevalence persists or even increases in some communities and districts. To increase understanding of MDA impact, we investigated the prevalence of active trachoma and ocular C. trachomatis prevalence, organism load, and circulating strains at baseline and one-year post-MDA in The Gambia and Senegal.

Methods
Pre- and one-year post-MDA, children aged 0–9 years were examined for clinical signs of trachoma in six Gambian and 12 Senegalese villages. Ocular swabs from each child’s right conjunctiva were tested for evidence of ocular C. trachomatis infection and organism load (ompA copy number), and ompA and multi-locus sequence typing (MLST) was performed.

Results
A total of 1171 children were examined at baseline and follow-up in The Gambia. Active trachoma prevalence decreased from 23.9% to 17.7%, whereas ocular C. trachomatis prevalence increased from 3.0% to 3.8%. In Senegal, 1613 and 1771 children were examined at baseline and follow-up, respectively. Active trachoma prevalence decreased from 14.9% to 8.0%, whereas ocular C. trachomatis prevalence increased from 1.8% to 3.6%. Higher organism load was associated with having active trachoma and severe inflammation. Sequence typing demonstrated that all Senegalese samples were genovar A, whereas Gambian samples were a mix of genovars A and B. MLST provided evidence of clustering at village and household levels and demonstrated differences of strain variant frequencies in Senegal, indicative of an “outbreak”. MLST, including partial ompA typing, provided greater discriminatory power than complete ompA typing.

Conclusions
We found that one round of MDA led to an overall decline in active trachoma prevalence but no impact on ocular C. trachomatis infection, with heterogeneity observed between villages studied. This could not be explained by MDA coverage or number of different circulating strains pre- and post-MDA. The poor correlation between active trachoma and infection prevalence supports the need for further work on alternative indicators to clinical signs for diagnosing ocular C. trachomatis infection. MLST typing has potential molecular epidemiology utility, including better understanding of transmission dynamics, although relationship to whole-genome sequence variability requires further exploration.
Freshwater snails of biomedical importance in the Niger River Valley: evidence of temporal and spatial patterns in abundance, distribution and infection with Schistosoma spp.
Authors: Rabone Muriel , Wiethase Joris Hendrik , Allan Fiona , Gouvras Anouk Nathalie , Pennance Tom , Hamidou Amina Amadou , Webster Bonnie Lee , Labbo Rabiou , Emery Aidan Mark , Garba Amadou Djirmay , Rollinson David 
Published: October 2019

Abstract

Background
Sound knowledge of the abundance and distribution of intermediate host snails is key to understanding schistosomiasis transmission and to inform effective interventions in endemic areas.

Methods
A longitudinal field survey of freshwater snails of biomedical importance was undertaken in the Niger River Valley (NRV) between July 2011 and January 2016, targeting Bulinus spp. and Biomphalaria pfeifferi (intermediate hosts of Schistosoma spp.), and Radix natalensis (intermediate host of Fasciola spp.). Monthly snail collections were carried out in 92 sites, near 20 localities endemic for S. haematobium. All bulinids and Bi. pfeifferi were inspected for infection with Schistosoma spp., and R. natalensis for infection with Fasciola spp.

Results
Bulinus truncatus was the most abundant species found, followed by Bulinus forskalii, R. natalensis and Bi. pfeifferi. High abundance was associated with irrigation canals for all species with highest numbers of Bulinus spp. and R. natalensis. Seasonality in abundance was statistically significant in all species, with greater numbers associated with dry season months in the first half of the year. Both B. truncatus and R. natalensis showed a negative association with some wet season months, particularly August. Prevalences of Schistosoma spp. within snails across the entire study were as follows: Bi. pfeifferi: 3.45% (79/2290); B. truncatus: 0.8% (342/42,500); and B. forskalii: 0.2% (24/11,989). No R. natalensis (n = 2530) were infected. Seasonality of infection was evident for B. truncatus, with highest proportions shedding in the middle of the dry season and lowest in the rainy season, and month being a significant predictor of infection. Bulinus spp. and Bi. pfeifferi showed a significant correlation of snail abundance with the number of snails shedding. In B. truncatus, both prevalence of Schistosoma spp. infection, and abundance of shedding snails were significantly higher in pond habitats than in irrigation canals.

Conclusions
Evidence of seasonality in both overall snail abundance and infection with Schistosoma spp. in B. truncatus, the main intermediate host in the region, has significant implications for monitoring and interrupting transmission of Schistosoma spp. in the NRV. Monthly longitudinal surveys, representing intensive sampling effort have provided the resolution needed to ascertain both temporal and spatial trends in this study. These data can inform planning of interventions and treatment within the region.
Bacillus pumilus probiotic feed supplementation mitigates Lawsonia intracellularis shedding and lesions
Authors: Opriessnig Tanja , Karuppannan Anbu K. , Beckler Dana , Ait-Ali Tahar , Cubas-Atienzar Ana , Halbur Patrick G. 
Published: October 2019

Abstract
The causative agent of ileitis, Lawsonia intracellularis, is commonly associated with diarrhea and reduced weight gain in growing pigs. The effect of in-feed probiotics on L. intracellularis infection dynamics was evaluated. In brief, 70 2.5-week-old-pigs were randomly divided into six groups with 10–20 pigs each. All pigs were fed an age appropriate base ration for the duration of the study, which was supplemented with one of three Bacillus strains including B. amyloliquefaciens (T01), B. licheniformis (T02) and B. pumilus (T03). Another group was orally vaccinated with a commercial live L. intracellularis vaccine (VAC) at 3 weeks of age. At 7 weeks of age, T01-LAW, T02-LAW, T03-LAW, VAC-LAW and the POS-CONTROL groups were challenged with L. intracellularis while the NEG-CONTROL pigs were not challenged. All pigs were necropsied 16 days later. By the time of inoculation, all VAC-LAW pigs had seroconverted and at necropsy 10–65% of the pigs in all other challenged groups were also seropositive. The results indicate a successful L. intracellularis challenge with highest bacterial DNA levels in POS-CONTROL pigs, VAC-LAW pigs and T01-LAW pigs. There was a delay in onset of shedding in T02-LAW and T03-LAW groups, which was reflected in less severe macroscopic and microscopic lesions, reduced intralesional L. intracellularis antigen levels and a lower area under the curve for bacterial shedding. Under the study conditions, two of the probiotics tested suppressed L. intracellularis infection. The obtained findings show the potential of probiotics in achieving antibiotic-free control of L. intracellularis.
Differences in patients derived from otolaryngology and other specialties with sleep apnea
Authors: Salas Constanza , Dreyse Jorge , Contreras Andrea , Nazar Gonzalo , Astorquiza Constanza , Cabezon Rodrigo , Labarca Gonzalo , Jorquera Jorge 
Published: October 2019

Background Snoring is a main concern in patients who consult an otolaryngologist (ENT physicians) and patients who have cardiovascular comorbidities or excessive daytime sleepiness who usually consult with other specialists. The aim of this study was to describe the clinical differences in patients with obstructive sleep apnea (OSA) referred from ENT or other specialists. Methods A prospective study was carried out between June 2015 and July 2018 in a tertiary center. We included patients with suspected OSA referred by the Home Sleep Apnea Test (HSAT) from different specialties such as ENT or other specialties. The main outcome measures of our study were demographic characteristics, clinical characteristics, sleep questionnaire results and HSAT results between OSA patients referred from ENT or other specialists. We used a t-test and chi-squared test for analysis. The diagnostic accuracy of the sleep questionnaires was achieved using receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results A total of 481 patients were included. OSA was occurred in 82.4% of the subjects (90 in ENT and 306 in other specialties). Patients with OSA referred from other specialists were older than ENT patients (55 ± 13 vs 44 ± 12; p < 0.001), there was more obesity (IMC 31 ± 5.0 vs 28.7 ± 3.8; p < 0,001), a larger neck circumference (42.2 cm ± 3.7 vs 40.6 cm ± 3.0; p < 0.001) and more reported comorbidities (p < 0.001). ENT patients reported mild OSA (46% vs 31%, p = 0.015) and more positional apnea (62% vs 39%, p = 0.002). In this group, the STOP-BANG questionnaire showed an AUC 0.695 vs AUC 0.804, and for sensitivity, the best cutoff was 4 points. Patients referred from otorhinolaryngology are different from those referred from other specialties. Clinical evaluation and screening of OSA should be patient-centered according to these clinical findings.