bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial etiology of lower respiratory tract infection in a Chinese large teaching hospital from 2015 to 2019
Authors: Tian Lei , Zhang Zhen , He Feng , sun ziyong 
Published: December 2019

Abstract
Background Sputum is the most common specimen type of lower respiratory tract in China, but its cultivation result is easily confused by the bacteria colonized in the oral cavity and pharynx. And it is very difficult to evaluate the clinical significance of sputum culture results both for clinicians and microbiologists. Bronchoscope alveolus lavage fluid(BALF)is a good specimen, which can accurately reflect the situation of lower respiratory tract infections (LRIs).Methods The accumulated data of BALF culture and antimicrobial susceptibility test in our hospital from January 2015 to October 2019 were reviewed and analyzed.Results The positive rate of BALF culture in our hospital was 18.3% (3467/18935) in 2015-2019. The most common pathogens were Klebsiella pneumoniae (18.1%, 627/3467), Pseudomonas aeruginosa (16.9%, 587/3467) and Acinetobacter baumannii (14.0%, 485/3467). For the eight most common pathogens, 40-70 years old was the highest age of distribution, but for Escherichia coli and Streptococcus pneumoniae, 0-5 years old was also the higher age of distribution. The antibiotic resistance rate of K. pneumoniae to imipenem and meropenem was 30.6% and 30.8%, respectively. The sensitivity of P. aeruginosa to antibiotics other than minocycline and ticarcillin clavulanic acid was all more than 60%. However, the resistance rate of A. baumannii to antibiotics other than tegacyclin and minocycline was all more than 80%.Conclusions 40-70 years old was the high incidence age of lower respiratory tract bacterial infection. K. pneumoniae resistant to carbapenems ( CR-K. pneumoniae ) and A. baumannii were a great challenge to clinical treatment and bacterial resistance control.
DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage
Authors: Xu Yang , Nowrangi Derek , Liang Hui , Wang Tian , Yu Lingyan , Lu Tai , Lu Zhengyang , Zhang John H. , Luo Benyan , Tang Jiping 
Published: December 2019

Abstract
Background Intracerebral hemorrhage (ICH) is the most devastating stroke subtype, with a poor prognosis and few proven treatments. Neuroinﬂammation is associated with ICH-induced brain injury and unfavorable outcomes. There is growing evidence that dinkkopf (DKK) 3 plays a key role in the adaptive anti-inflammatory and neuroprotective responses following intracerebral hemorrhage. This study aimed to evaluate the protective effects of DKK3 against brain edema and neuroinflammation in a mice model of ICH.Methods Male, adult CD1 mice were subjected to sham or ICH surgery using a collagenase injection model. ICH animals received either recombinant DKK3, Kremen-1 siRNA, or DVL-1 siRNA. The neurobehavioral deficits were evaluated at 24 h, 72 h, and 28 days after ICH induction. Western blot and immunofluorescence were employed to examine the expression and localization of DKK3, Kremen-1, Dishevelled-1 (DVL-1), c-JUN N-terminal kinase (JNK), Activator protein-1 (AP-1), cleaved caspase-1, NF-κB, and IL-1β in the brain.Results The expression of endogenous DKK3 and DVL-1 was transiently decreased after ICH compared to that in the sham group. Compared to the mice of ICH, exogenous rDKK3 administration reduced the brain water content and affected the neurological functions in ICH mice. Moreover, DKK3 was colocalized with Kremen-1 in microglia. Using a Kremen-1 or DVL-1 siRNA-induced in vivo knockdown approach, we demonstrated that the effects of DKK3 against ICH were mediated, at least partly, by the Kremen-1 and DVL-1 pathways.Conclusions DKK3 improves the neurological outcomes, potentially by decreasing JNK/AP-1 mediated inflammation, thereby ameliorating the short- and long-term sequelae after ICH.
Eimeria tenella Eimeria-specific protein that interacts with apical membrane antigen 1 (EtAMA1) is involved in host cell invasion
Authors: Li Cong , Zhao Qiping , Zhu Shunhai , Wang Qingjie , Wang Haixia , Yu Shuilan , Yu Yu , Liang Shashan , Zhao Huanzhi , Huang Bing , Dong Hui , Han Hongyu 
Published: December 2019

Abstract
Apical membrane antigen 1 (AMA1), which is released from micronemes and is conserved across all apicomplexans, plays a central role in the host cell invasion. In this study, we characterized one putative Et AMA1-interacting protein, E. tenella Eimeria -specific protein ( Et Esp). The interaction between Et AMA1 and Et Esp was confirmed with bimolecular fluorescence complementation (BiFC) in vivo and by glutathione S-transferase (GST) fusion protein pull-down (GST pull-down) in vitro . We showed that Et Esp is differentially expressed during distinct phases of the parasite life cycle by using qPCR and western blotting. Immunoﬂuorescence analysis showed that the Et Esp protein is mainly distributed on the parasite surface, and that the expression of this protein increases during the development of the parasite in the host cells. Using staurosporine, we showed that Et Esp is a micronemal protein secreted by sporozoites. In inhibition tests, a polyclonal anti-r Et Esp antibody attenuated the capacity of E. tenella to invade host cells in vitro . These data have implications for the use of Et AMA1 or Et AMA1-interacting proteins as targets in intervention strategies against avian coccidiosis.
Hox gene expression during development of the phoronid Phoronopsis harmeri
Authors: Gąsiorowski Ludwik , Hejnol Andreas 
Published: December 2019

Abstract
Background: Phoronida is a small group of marine worm-like suspension feeders, which together with brachiopods and bryozoans form the clade Lophophorata. Although their development is well studied on the morphological level, data regarding gene expression during this process are scarce and restricted to the analysis of relatively few transcription factors. Here we present a description of the expression patterns of Hox genes during the embryonic and larval development of the phoronid Phoronopsis harmeri.Results: We identified sequences of 8 Hox genes in the transcriptome of Ph. harmeri and determined their expression pattern during embryonic and larval development using whole mount in situ hybridization. We found that none of the Hox genes is expressed during embryonic development. Instead their expression is initiated in the later developmental stages, when the larval body is already formed. The Hox genes are expressed in the non-collinear manner in the posterior body of the larvae: in the telotroch and the structures that represent rudiments of the adult worm, which emerges through the process of drastic metamorphosis. Additionally, we found that certain head-specific transcription factors are expressed in the oral hood, apical organ, anterior digestive system and developing larval tentacles, anterior to the Hox-expressing territories.Conclusions: The lack of Hox gene expression during early development of Ph. harmeri indicates that the larval body develops without positional information of the Hox patterning system. Such phenomenon might be a consequence of the evolutionary intercalation of the larval form into an ancestral life cycle of phoronids. The observed Hox gene expression can also be a consequence of the actinotrocha representing a “head larva”, which is composed of the most anterior body region that is devoid of Hox gene expression, which is supported by the expression of head-specific transcription factors. This implies that the Hox patterning system is used for the positional information of the trunk rudiments and is, therefore, delayed to the later larval stages. We propose that a new body form was intercalated to the phoronid life cycle by precocious development of the anterior structures or by delayed development of the trunk rudiment in the ancestral phoronid larva.
The increased recurrence rate of liver abscess caused by extended-spectrum β-lactamase-producing Klebsiella pneumoniae
Authors: Chang Zhihui , Ren Yue , Wang Hairui , Liu Zhaoyu 
Published: December 2019

Abstract
Background The pathogenic bacterium Klebsiella pneumoniae (KP) is the major causative agent of pyogenic liver abscess (PLA). But reports about the prognosis of KP-caused PLA (KPLA) are rare. This study aimed to ascertain the recurrence rate of KPLA after initial treatment, and its contributing factors.Methods The medical records data were retrospectively analyzed of KPLA patients who were admitted to Shengjing Hospital of China Medical University from January 2012 to January 2018. According to whether or not there was recurrence of KPLA during follow-up, the patients were divided into a ‘recurrence’ and a ‘non-recurrence’ group. The clinical and CT characteristics of patients were compared between the two groups, and those factors related to KPLA recurrence were further analyzed.Results A total of 110 patients who had first-time episodes of KPLA were included into the study. The average follow-up time was 3.65±2.18 years. Twenty (18.18%) KPLA patients experienced recurrence. Those in the recurrence group had a significantly greater incidence of extended-spectrum β-lactamase (ESBL) production compared to the non-recurrence group (30.0% vs 8.89%, P=0.018). Diabetes, biliary tract disease, and history of malignancy was not associated with recurrence (all P>0.05). No difference in the CT characteristics of KPLA (including abscess size, location, whether multilocular, gas production of KPLA, and thrombophlebitis) was found between the two groups. Multivariate regression analysis showed that ESBL production (OR, 6.3; 95% CI, 1.02–38.59; P=0.04) was an independent risk factor for the recurrence of KPLA.Conclusions KPLA has a high recurrence rate, and ESBL production is a risk factor for recurrent KPLA.
Identification of Four New Mutations in Chilean Patients with Various Forms of Maple Syrup Urine Disease and Genotype-Phenotype Correlations
Authors: Campanholi Diana Ruffato Resende , Margutti Ana Vitoria Barban , Silva Wilson Araújo , Garcia Daniel Fantozzi , Molfetta Greice Andreotti de , Marques Adriana Aparecida , Schwartz Ida Vanessa Döederlein , Cornejo Veronica , Hamilton Valerie , Castro Gabriela , Borges Ester Simon , Junior José Simon Camelo 
Published: December 2019

Abstract
Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes in a cohort of Chilean MSUD patients, and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 18 MSUD patients was carried out using PCR and DNA sequencing. Results: Four new pathogenic mutations were identified in the 18 patients that were analyzed: one in BCKDHA (p.Thr338Ile); two in BCKDHB (p.Gly336Ser e p.Pro240Thr); and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in the analyzed patients have been described previously. Conclusion: There were no correlations observed between genotypes and phenotypes. Thus, if MSUD is diagnosed more promptly, such as in neonatal screening, it might be possible to establish genotype-phenotype relationships more efficiently. Keywords: inborn errors of metabolism; maple syrup urine disease; branched-chain amino acids; valine; leucine; isoleucine.
Analytical Strategies for Failure Time Data with a Cured Fraction
Authors: An Sheng-li , Huang Fuqiang , Kang Pei , Liu Yingxin 
Published: December 2019

Abstract
Some failure time data come from a population that consists of some subjects who are susceptible to and others who are non-susceptible to the event of interest. The data typically have heavy censoring at the end of the follow-up period, and a traditional survival analysis would not always be appropriate, yet it is commonly seen in literatures. For such kind of data, we carry out simulation studies to compare the performances of the Cox’s PH model with the proportional hazards mixture cure (PHMC) model and the accelerated failure model (AFT model) with the AFT mixture cure (AFTMC) model respectively. Then we apply the models to the datasets of Lung Cancer and Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E1684. The conclusions are as follows. The PHMC model and the AFTMC model do not have obvious advantages for time-to-event data without a cured fraction. In this case, it is recommended to use the Cox’s PH model or AFT model for analysis. If some subjects are non-susceptible to the event of interest in the data, it is recommended to use the PHMC model or AFTMC model for analysis, however, which may need a sufficient sample size.
Keywords: Cox’s PH model; PHMC model; AFT model; AFTMC model; cure model
Pneumococcal Carriage and Antibiotic Susceptibility Patterns in Mother-Baby Pairs in a rural community in Eastern Uganda
Authors: Akech Gabriel Madut , Naloli Mercy , Sebwami Paul , Kazibwe Patrick , Atwikiriize Maureen , Onyait Julius , Oboth Paul , Nteziyaremye Julius , Nekaka Rebecca , Iramiot Jacob Stanley 
Published: December 2019

Abstract
Objective: This study aimed to estimate pneumococcal carriage and determine antibiotic susceptibility patterns of the pneumococci isolated in the mother-baby pairs in Ngora district after the roll out of the pneumococcal vaccine. We hypothesized that high carriage of S. pneumoniae in mothers leads to carriage in their babies and hence a greater chance of contacting pneumoniae. Results: Consecutive sampling technique was used to select 152 mother-baby pairs from the community visits and those seeking care at the health facility. We collected nasal swabs from both baby and mother for culture and sensitivity using the Kirby-Bauer’s agar disc diffusion method. This study found that there was a low prevalence of pneumococcal carriage in the mother-baby pair in Ngora district. We also observed high rates microbial resistance to Penicillin which is the first-line management of pneumonia in Uganda. The relationship between pneumococcal carriage and immunization status suggest that Pneumococcal vaccine is protective against pneumococcal carriage. Resistance of S. pneumoniae to the commonly used antibiotics was high. Key words: Pneumococcal carriage, mother-baby pair, antibiotic susceptibility pattern, immunization with PCV 10, Eastern Uganda.
Rare GermlineGLMNVariants Identified from Blue Rubber Bleb Nevus Syndrome Might Impact mTOR Signaling
Authors: Yin Jie , Qin Zhongping , Wu Kai , Zhu Yufei , Hu Landian , Kong Xiangyin 
Published: December 2019

Backgrounds and Objective:Blue rubber bleb nevus syndrome (BRBN) or Bean syndrome is a rare Venous Malformation (VM)-associated disorder, which mostly affects the skin and gastrointestinal tract in early childhood. Somatic mutations in TEK have been identified from BRBN patients; however, the etiology of TEK mutation-negative patients of BRBN need further investigation.Method:Two unrelated sporadic BRBNs and one sporadic VM were firstly screened for any rare nonsilent mutation in TEK by Sanger sequencing and subsequently applied to whole-exome sequencing to identify underlying disease causative variants. Overexpression assay and immunoblotting were used to evaluate the functional effect of the candidate disease causative variants.Results:In the VM case, we identified the known causative somatic mutation in the TEK gene c.2740C>T (p.Leu914Phe). In the BRBN patients, we identified two rare germline variants in GLMN gene c.761C>G (p.Pro254Arg) and c.1630G>T(p.Glu544*). The GLMN-P254R-expressing and GLMN-E544X-expressing HUVECs exhibited increased phosphorylation of mTOR-Ser-2448 in comparison with GLMN-WTexpressing HUVECs in vitro.Conclusion:Our results demonstrated that rare germline variants in GLMN might contribute to the pathogenesis of BRBN. Moreover, abnormal mTOR signaling might be the pathogenesis mechanism underlying the dysfunction of GLMN protein.
The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities
Authors: Xu Dixon H. , Cullen Benjamin D. , Tang Meng , Fang Yujiang 
Published: December 2019

Background:
Peripheral neuropathy can significantly impact the quality of life for those
who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom
relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the
treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in
the management of neuropathic pain was examined in this four-week, randomized and placebocontrolled
trial.

Methods:
In total, 29 patients with symptomatic peripheral neuropathy were recruited and enrolled. 15
patients were randomized to the CBD group with the treatment product containing 250 mg CBD/3 fl.
oz, and 14 patients were randomized to the placebo group. After four weeks, the placebo group was
allowed to crossover into the treatment group. The Neuropathic Pain Scale (NPS) was administered
biweekly to assess the mean change from baseline to the end of the treatment period.

Results:
The study population included 62.1% males and 37.9% females with a mean age of 68 years.
There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in
the CBD group when compared to the placebo group. No adverse events were reported in this study.

Conclusions:
Our findings demonstrate that the transdermal application of CBD oil can achieve significant
improvement in pain and other disturbing sensations in patients with peripheral neuropathy. The
treatment product was well tolerated and may provide a more effective alternative compared to other
current therapies in the treatment of peripheral neuropathy.
N-alpha-Aminoacyl Colchicines as Promising Anticancer Agents
Authors: Marzo-Mas Ana , Conesa-Milián Laura , Noppen Sam , Liekens Sandra , Falomir Eva , Murga Juan , Carda Miguel , Marco Juan A. 
Published: December 2019

Background:
In the last years, many efforts have been made to find colchicine derivatives
with reduced toxicity. Additionally, the deregulation of amino acid uptake by cancer cells
provides an opportunity to improve anticancer drug effectiveness.

Objective:
To design new colchicine derivatives with reduced cytotoxicity and enhanced selectivity
by means of introducing aminoacyl groups.

Method:
34 colchicine analogues bearing L- and D-amino acid pendants were synthetized and
characterized by NMR, IR and MS techniques. Cytotoxicity and antimitotic properties were assessed
by spectrophotometry and cell cycle assays. Oncogene downregulation was studied by RTqPCR
whereas in vivo studies were performed in SCID mice.

Results:
Compounds exhibit high antiproliferative activities at the nanomolar level while being, in
general, less cytotoxic than colchicine. Most compounds inhibit the polymerization of tubulin in a
way similar to colchicine itself, with L-amino acid derivatives being the most active in the inhibition
of tubulin polymerization. All selected compounds caused cell cycle arrest at the G2/M phase
when tested at 1 μM. More specifically, Boc-L-proline derivative 6 arrested half of the population
and showed one of the highest Selectivity Indexes. Derivatives 1 (Boc-glycine), 27 (D-leucine)
and 31 (Boc-glycine-glycine) proved fairly active in downregulating the expression of the c-Myc,
hTERT and VEGF oncogenes, with compound 6 (Boc-L-proline) having the highest activity. This
compound was shown to exert a potent anti-tumor effect when administered intraperitoneally
(LD50 > 100 mg/kg for 6, compared with 2.5 mg/kg for colchicine).

Conclusion:
Compound 6 offers an opportunity to be used in cancer therapy with less toxicity
problems than colchicine.
Prototipe buku ajar fisika dasar reflektif-integratif berbasis problem solving untuk meningkatkan pengetahuan metakognisi
Authors: Asy'ari Muhammad , Hidayat Samsun , Muhali Muhali 
Published: December 2019

This study aims to evaluate the validity and effectiveness of the reflective-integrative basic physics textbook prototype based on problem-solving to improve metacognition knowledge. This research is a quasi-experimental study with one group pretest-posttest design in 25 physics education students of FPMIPA IKIP Mataram. Descriptive and statistical analysis using the n-gain equation and paired samples test was conducted to evaluate the validity and effectiveness of the product. Product validity was assessed by two competent experts using validation sheets and analyzed descriptively, while product effectiveness was measured after learning using essay test instruments that were analyzed descriptively and statistically using paired samples test. The results showed that the reflective-integrative basic physics textbook prototype based on problem-solving was valid (3.38) and reliable (0.97), while declarative knowledge (n-gain = 0.58), procedural knowledge (n-gain = 0.53), and conditional knowledge (n-gain = 0.56) was increased after learning in the medium category. Statistical test results showed that the reflective-integrative basic physics textbook prototype based on problem-solving had a significant effect (p <0.05) on the students' metacognition knowledge. Based on these findings it can be concluded that the reflective-integrative basic physics textbook prototype based on problem-solving was valid and effective to improve students' metacognition knowledge.
Pengembangan kamus bahasa Jawa digital berbasis android
Authors: Insani Nur Hanifah , Mulyana Mulyana 
Published: December 2019

Penelitian ini bertujuan untuk mengembangkan media pembelajaran bahasa Jawa digital berbasis android serta mengetahui kualitas produk media pembelajaran bahasa Jawa berbasis android. Jenis penelitian ini merupakan penelitian pengembangan (R&D) yang diadaptasi dari Borg & Gall dengan model prosedural yang terdiri dari tahap pendahuluan, tahap pengembangan produk, serta tahap evaluasi (ujicoba) produk. Penilaian produk dilakukan oleh ahli media, ahli materi, guru bahasa Jawa, dan peserta didik. Teknik pengumpulan data menggunakan kuesioner kemudian data dianalisis secara deskriptif kuantitatif. Hasil penelitian menunjukkan bahwa produk media pembelajaran kamus bahasa Jawa berbasis android termasuk dalam kategori baik sekali. Demikian juga ahli media, ahli materi, juga guru bahasa Jawa menilai kualitas multimedia pembelajaran bahasa Jawa baik sekali. Para siswa juga sangat setuju dengan adanya mulitmedia kamus bahasa Jawa digital berbasis android. Berdasarkan hasil tersebut, maka produk kamus bahasa Jawa digital berbasis android sangat layak digunakan dalam pembelajaran bahasa Jawa. Developing android-based javanese digital dictionary AbstractThis research aims to develop android-based Javanese digital dictionary and to reveal the quality of android-based Javanese digital dictionary. The study is a research and development adapted from Borg and Gall that consist of preliminary studies, product development, and evaluating the product. The product assessment was conducted by a media expert, a material expert, Javanese teachers and the students. The data collecting technique was done by using questionnaires, then it was analysed using descriptice quantitative technique. The results of this research show that the product resulted of developing android-based Javanese digital dictionary falls into the category of very good. From the view of experts in media and material also Javanese teacher rates the quality of the multimedia is very good. The students also very agree with the product has been made. Based on the results, the product of android-based Javanese digital dictionary is very feasible to be used in Javanese learning.