bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing a customized clinical practice guideline regarding antibiotic prophylaxis for Iranian general dentists
Authors: Savadi Najmeh , Barati Omid , Mirhadi Hossein , Golkari Ali 
Published: October 2019

AbstractBackgroundClinical practice guidelines produced by developed countries seemed to be not completely feasible for developing countries due to their different local context. In this study, we designed a customized guideline about antibiotic prophylaxis before dental procedures for Iranian general dentists.MethodsThis study was conducted of two parts, including a qualitative part and a cross-sectional analytic part. A multidisciplinary team searched for related guidelines and other documents, selected the most updated and high quality ones, customized their recommendations based on available antibiotics in Iran, prepared a draft adapted guideline and summarized its recommendations in 3 flowcharts. An expert panel (20 specialists of four Iranian dental universities) participated in a consensus process, afterwards to determine the relevance and clarity of the flowcharts and their items. Then the Content Validity Indices (CVIs) were calculated and any items with CVI higher than 0.79 remained.ResultsThe adapted recommendations were summarized in flowcharts A to C. Two separate groups of patients who need antibiotic prophylaxis were presented in flowchart A; including those with high risk for distant-site infection (infective endocarditis and prosthetic joint infection) and those at risk for poor healing and orofacial infection (due to impaired immunologic function). Flowcharts B and C described antibiotic regimen and also the dental procedures where antibiotic prophylaxis was needed for mentioned groups. The content validity indices and the percentages of agreement between the expert panel members were considerably high.ConclusionsA localized, clear and straight forward guideline that addresses all groups of dental patients who need antibiotic prophylaxis has been produced for Iranian general dentists.
Uptake of a fluorescently tagged chloroquine analogue is reduced in CQ-resistant compared to CQ-sensitive Plasmodium falciparum parasites
Authors: Reiling Sarah J. , Rohrbach Petra 
Published: October 2019

Abstract

Background
Chloroquine (CQ) was the drug of choice for decades in the treatment of falciparum malaria until resistance emerged. CQ is suggested to accumulate in the parasite’s digestive vacuole (DV), where it unfolds its anti-malarial properties. Discrepancies of CQ accumulation in CQ-sensitive (CQS) and CQ-resistant (CQR) strains are thought to play a significant role in drug susceptibility. Analysis of CQ transport and intracellular localization using a fluorescently tagged CQ analogue could provide much needed information to distinguish susceptible from resistant parasite strains. The fluorescently tagged CQ analogue LynxTag-CQ™GREEN (CQGREEN) is commercially available and was assessed for its suitability.

Methods
IC50 values were determined for both CQ and CQGREEN in two CQS and two CQR Plasmodium falciparum strains. Buffer solutions with varying pH were used to determine pH-dependent localization of CQGREEN in infected red blood cells. Before CQS or CQR parasites were exposed to different pH buffers, they were pre-loaded with varying concentrations of CQGREEN for up to 7 h. Intracellular accumulation was analysed using live cell confocal microscopy. CQGREEN uptake rates were determined for the cytosol and DV in the presence and absence of verapamil.

Results
In CQS strains, twofold higher IC50 values were determined for the CQGREEN analogue compared to CQ. No significant differences in IC50 values were observed in CQR strains. Addition of verapamil reversed drug resistance of CQR strains to both CQ and CQGREEN. Live cell imaging revealed that CQGREEN fluorescence was mainly seen in the cytosol of most parasites, independent of the concentration used. Incubation periods of up to 7 h did not influence intracellular localization of CQGREEN. Nevertheless, CQGREEN uptake rates in CQR strains were reduced by 50% compared to CQS strains.

Conclusion
Although fluorescence of CQGREEN was mainly seen in the cytosol of parasites, IC50 assays showed comparable efficacy of CQGREEN and CQ in parasite killing of CQS and CQR strains. Reduced uptake rates of CQGREEN in CQR strains compared to CQS strains indicate parasite-specific responses to CQGREEN exposure. The data contains valuable information when CQGREEN is used as an analogue for CQ.
Prevalence and distribution of G6PD deficiency: implication for the use of primaquine in malaria treatment in Ethiopia
Authors: Lo Eugenia , Zhong Daibin , Raya Beka , Pestana Kareen , Koepfli Cristian , Lee Ming-Chieh , Yewhalaw Delenasaw , Yan Guiyun 
Published: October 2019

Abstract

Background
G6PD enzyme deficiency is a common enzymatic X-linked disorder. Deficiency of the G6PD enzyme can cause free radical-mediated oxidative damage to red blood cells, leading to premature haemolysis. Treatment of Plasmodium vivax malaria with primaquine poses a potential risk of mild to severe acute haemolytic anaemia in G6PD deficient people. In this study, the prevalence and distribution of G6PD mutations were investigated across broad areas of Ethiopia, and tested the association between G6PD genotype and phenotype with the goal to provide additional information relevant to the use of primaquine in malaria treatment.

Methods
This study examined G6PD mutations in exons 3–11 for 344 febrile patient samples collected from seven sites across Ethiopia. In addition, the G6PD enzyme level of 400 febrile patient samples from Southwestern Ethiopia was determined by the CareStart™ biosensor. The association between G6PD phenotype and genotype was examined by Fisher exact test on a subset of 184 samples.

Results
Mutations were observed at three positions of the G6PD gene. The most common G6PD mutation across all sites was A376G, which was detected in 21 of 344 (6.1%) febrile patients. Thirteen of them were homozygous and eight were heterozygous for this mutation. The G267+119C/T mutation was found in 4 (1.2%) individuals in South Ethiopia, but absent in other sites. The G1116A mutation was also found in 4 (1.2%) individuals from East and South Ethiopia. For the 400 samples in the south, 17 (4.25%) were shown to be G6PD-deficient. G6PD enzyme level was not significantly different by age or gender. Among a subset of 202 febrile patients who were diagnosed with malaria, 11 (5.45%) were G6PD-deficient. These 11 infected samples were diagnosed with Plasmodium vivax by microscopy. Parasitaemia was not significantly different between the G6PD-deficient and G6PD-normal infections.

Conclusions
The prevalence of G6PD deficiency is modest among febrile patients in Ethiopia. G6PD deficiency testing is thus recommended before administrating primaquine for radical cure of P. vivax infected patients. The present study did not indicate a significant association between G6PD gene mutations and enzyme levels.
A successful intraoperative diagnosis of coexisting lymphoma and endometrial cancer
Authors: Yoshino Ai , Kobayashi Eiji , Shiomi Mayu , Sato Kazuaki , Ichii Michiko , Ueda Yutaka , Kimura Tadashi 
Published: October 2019

Abstract

Background
The coexistence of hematological malignancy with endometrial cancer is a rare phenomenon. We report a case of coexistence of endometrial cancer with follicular lymphoma which we suspected preoperatively and diagnosed during surgery by a multidisciplinary intraoperative assessment.

Case presentation
A 67-year-old woman was referred to our hospital due to a suspicion of an endometrial cancer. Endometrial biopsy revealed grade 1 endometrioid adenocarcinoma. MRI showed invasion of the tumor into the outer half of the myometrium, and abdominal CT showed para-aortic and atypical mesentery lymphadenopathy which was suspected to be metastasis of endometrial cancer or malignant lymphoma. Abdominal hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, partial omentectomy, and mesentery lymph node biopsy for endometrial cancer were performed. The mesentery and para-aortic lymph nodes that were sent for frozen section analysis showed no metastasis of the endometrial cancer. We simultaneously conducted an unusual intraoperative emergent four-color flow cytometry and intraoperatively diagnosed a B cell lymphoma in the mesenteric lymph nodes. Because this multidisciplinary assessment, we were able to avoid an unnecessary intestinal resection. The final pathological diagnosis was an endometrioid carcinoma (G1, FIGO stage IA), with a synchronous follicular lymphoma.

Conclusion
Although a rare event in endometrial cancer surgery, it is necessary to be alert to the possibility of a synchronous lymphoma in cases of unusual site adenopathy.
Molecular detection of Anaplasma phagocytophilum in wild carnivores in north-eastern Poland
Authors: Szewczyk Tomasz , Werszko Joanna , Myczka Anna W. , Laskowski Zdzisław , Karbowiak Grzegorz 
Published: October 2019

Abstract

Background
Anaplasma phagocytophilum is an obligate parasitic intracellular bacterium. It is the causative agent of granulocytic anaplasmosis, with effects on human and animal health. In Europe, the pathogen is mainly transmitted among a wide range of vertebrate hosts by blood-sucking arthropods. The aim of this study was to determine the presence of A. phagocytophilum in wild carnivores, viz raccoon dogs (Nyctereutes procyonoides), badgers (Meles meles), foxes (Vulpes vulpes), martens (Martes sp.) and European polecats (Mustela putorius), using molecular methods.

Methods
In the present study, 174 spleen samples were collected from adult, wild carnivores hunted in the years 2013–2016. A short fragment (383 bp) of the 16S ribosomal RNA gene partial sequence was used as a marker to identify A. phagocytophilum in spleen samples collected from carnivores using nested PCR.

Results
The prevalence of A. phagocytophilum in wild carnivores was 31.61% (55/174). Seven sequences of A. phagocytophilum were generated from two raccoon dogs, two badgers, one marten, one red fox and one European polecat. Six identical nucleotide sequences were obtained from one raccoon dog, two badgers, one marten, one red fox and one European polecat (A. phagocytophilum sequences 1: MH328205–MH328209, MH328211), and these were identical to many A. phagocytophilum sequences in the GenBank database (100% similarity). The second sequence (A. phagocytophilum sequence 2: MH328210) obtained from the raccoon dog shared 99.74% identity with A. phagocytophilum sequence 1.

Conclusions
To our knowledge, this is the first study to use molecular methods to determine the presence of A. phagocytophilum in wild carnivores, viz raccoon dog, badger, marten and European polecat, in Poland. The detected A. phagocytophilum sequences (1 and 2) were closely related with those of A. phagocytophilum occurring in a wide range of wild and domestic animals and vectors.
Mycobacterium indicus pranii therapy induces tumor regression in MyD88- and TLR2-dependent manner
Authors: Kumar Pawan , Das Gobardhan , Bhaskar Sangeeta 
Published: October 2019

Abstract

Objectives
Mycobacterium indicus pranii (MIP) is an atypical mycobacterium species with potent antitumor efficacy. Macrophages and dendritic cells (DCs) are antigen-presenting cells, playing key roles in the activation of antitumor immunity. We have previously shown the potent activation of macrophages and DCs by MIP, which is mediated by MyD88–TLR2 signaling axis. In the present study, we further examined the role of MyD88 and TLR2 in MIP-mediated tumor regression.

Results
Wild-type and MyD88−/− mice were implanted with B16F10 tumor cells, treated with MIP or phosphate-buffered saline (PBS) and monitored for tumor growth. As expected, MIP therapy led to significant tumor regression in wild-type mice. However, antitumor efficacy of MIP was lost in MyD88−/− animals. Both PBS-treated (control) and MIP-treated MyD88−/− mice developed tumors with comparable volume. Since MyD88 relays TLR engagement signals, we analyzed the antitumor efficacy of MIP in TLR2−/− and TLR4−/− mice. It was observed that MIP therapy reduced tumor burden in wild-type and TLR4−/− mice but not in TLR2−/− mice. Tumor volume in MIP-treated TLR2−/− mice were comparable with those in PBS-treated wild-type animals. These results implicated the MyD88–TLR2 signaling axis in the antitumor efficacy of MIP.
Co-inhibition of HDAC and MLL-menin interaction targets MLL-rearranged acute myeloid leukemia cells via disruption of DNA damage checkpoint and DNA repair
Authors: Ye Jing , Zha Jie , Shi Yuanfei , Li Yin , Yuan Delin , Chen Qinwei , Lin Fusheng , Fang Zhihong , Yu Yong , Dai Yun , Xu Bing 
Published: October 2019

Abstract
While the aberrant translocation of the mixed-lineage leukemia (MLL) gene drives pathogenesis of acute myeloid leukemia (AML), it represents an independent predictor for poor prognosis of adult AML patients. Thus, small molecule inhibitors targeting menin-MLL fusion protein interaction have been emerging for the treatment of MLL-rearranged AML. As both inhibitors of histone deacetylase (HDAC) and menin-MLL interaction target the transcription-regulatory machinery involving epigenetic regulation of chromatin remodeling that governs the expression of genes involved in tumorigenesis, we hypothesized that these two classes of agents might interact to kill MLL-rearranged (MLL-r) AML cells. Here, we report that the combination treatment with subtoxic doses of the HDAC inhibitor chidamide and the menin-MLL interaction inhibitor MI-3 displayed a highly synergistic anti-tumor activity against human MLL-r AML cells in vitro and in vivo, but not those without this genetic aberration. Mechanistically, co-exposure to chidamide and MI-3 led to robust apoptosis in MLL-r AML cells, in association with loss of mitochondrial membrane potential and a sharp increase in ROS generation. Combined treatment also disrupted DNA damage checkpoint at the level of CHK1 and CHK2 kinases, rather than their upstream kinases (ATR and ATM), as well as DNA repair likely via homologous recombination (HR), but not non-homologous end joining (NHEJ). Genome-wide RNAseq revealed gene expression alterations involving several potential signaling pathways (e.g., cell cycle, DNA repair, MAPK, NF-κB) that might account for or contribute to the mechanisms of action underlying anti-leukemia activity of chidamide and MI-3 as a single agent and particularly in combination in MLL-r AML. Collectively, these findings provide a preclinical basis for further clinical investigation of this novel targeted strategy combining HDAC and Menin-MLL interaction inhibitors to improve therapeutic outcomes in a subset of patients with poor-prognostic MLL-r leukemia.
Virus persistence in pig herds led to successive reassortment events between swine and human influenza A viruses, resulting in the emergence of a novel triple-reassortant swine influenza virus
Authors: Chastagner Amélie , Bonin Emilie , Fablet Christelle , Quéguiner Stéphane , Hirchaud Edouard , Lucas Pierrick , Gorin Stéphane , Barbier Nicolas , Béven Véronique , Garin Emmanuel , Blanchard Yannick , Rose Nicolas , Hervé Séverine , Simon Gaëlle 
Published: October 2019

Abstract
This report describes the detection of a triple reassortant swine influenza A virus of H1avN2 subtype. It evolved from an avian-like swine H1avN1 that first acquired the N2 segment from a seasonal H3N2, then the M segment from a 2009 pandemic H1N1, in two reassortments estimated to have occurred 10 years apart. This study illustrates how recurrent influenza infections increase the co-infection risk and facilitate evolutionary jumps by successive gene exchanges. It recalls the importance of appropriate biosecurity measures inside holdings to limit virus persistence and interspecies transmissions, which both contribute to the emergence of new potentially zoonotic viruses.
Shock index in patients with traumatic solid organ injury as a predictor of massive blood transfusion protocol activation
Authors: El-Menyar Ayman , Jabbour Gaby , Asim Mohammad , Abdelrahman Husham , Mahmood Ismail , Al-Thani Hassan 
Published: October 2019

Abstract

Purpose
We aimed to assess the utility of shock index (SI) to predict the need for massive transfusion protocol (MTP) in patients with solid organ injury (SOI) in a Level 1 Trauma center.

Methods
We conducted a retrospective analysis for patients with SOI between 2011 and 2014. Patients were categorized according to on-admission SI into low (< 0.8) and high SI (≥0.8) group.

Results
A total of 4500 patients were admitted with trauma, of them 572 sustained SOIs (289 patients had SI ≥0.8). In comparison to low SI, patients with high SI were younger, had higher injury severity scores (ISS) and lower Trauma and Injury Severity Score (TRISS); (p < 0.001). The proportion of exploratory laparotomy (EXLap), blood transfusion (BT), MTP activation, sepsis and hospital mortality were significantly higher in patients with high SI. Serum lactate (r = 0.34), hematocrit (r = − 0.34), ABC score (r = 0.62), ISS (r = 0.35), and amount of transfused blood (r = 0.22) were significantly correlated with SI. On multivariable regression analysis using 9 relevant variables (age, sex, ISS, ED GCS, serum lactate, hematocrit, Abdomen AIS and Focused assessment with sonography in trauma (FAST) and SI), SI ≥ 0.8 was an independent predictor of BT (OR 2.80; 95%CI 1.56–4.95) and MTP (OR 2.81;95% CI 1.09–7.21) .

Conclusions
In patients with SOI, SI is a simple bedside predictor for BT and MTP activation. Further prospective studies are needed to support our findings.
Ethanol effects on 68Ga-radiolabelling efficacy and radiolysis in automated synthesis utilizing NaCl post-processing
Authors: Meisenheimer Michael , Kürpig Stefan , Essler Markus , Eppard Elisabeth 
Published: October 2019

Abstract

Objective
Recent studies showed that ethanol in the reaction mixture improves radiolabelling with trivalent radiometals in terms of precursor amount, reaction time, reaction temperature and radiolysis. With regard to clinical application, this effect is of practical interest in radiopharmacy. The aim of this study was to evaluate whether the positive effect of ethanol can be exploited in automated systems utilizing NaCl-post processing.

Methods
Gallium-68 was obtained from a 1.85 GBq 68Ge/68Ga-generator. Radiolabelling was performed on an automated 68Ga-labelling cassette module. The standard labelling protocol was used without modifications. 0–40 vol% ethanol were added to the reaction mixture. Quality control was performed using radioHPLC and radioTLC.

Results
Utilization of additional ethanol on an automated cassette module can be achieved by adding ethanol directly to the buffer solution without further modifications of the standard procedure. Radiolysis was decreased significantly as analysed by radioHPLC.

Conclusion
It was possible to combine the positive effects of ethanol on radiolabelling efficacy and radiolysis with the standard labelling procedure of an automated cassette module system. The whole process guarantees safe preparation of highly pure 68Ga-peptide for clinical application.
An overview of RNA virus-encoded microRNAs
Authors: Li Xihan , Zou Xiaoping 
Published: October 2019

Abstract
MicroRNAs (miRNAs) are a number of small non-coding RNAs playing a regulatory part in gene expression. Many virus-encoded miRNAs have been found, which manifests that viruses as well apply the basic pattern of gene regulation, however, mostly in viruses transcribed from double-stranded DNA genomes. It is still in dispute if RNA viruses could encode miRNAs because the excision of miRNA might result in the cleavage of viral RNA genome. We will focus on the miRNAs encoded by RNA virus and discuss their potential role in viral replication cycle and host cells.
Intestinal FDG-PET/CT imaging of an Eritrean with schistosomiasis seen in Denmark
Authors: Daghigh Ata , Grüner Julie Marie , Mørup Peter 
Published: October 2019

Abstract

Background
Schistosomiasis is one of the most common parasitic diseases in subtropical and tropical areas and still is considered of public health significance. This disease affects about 200 million people around the world. Intestinal schistosomiasis is mainly diagnosed by parasitological, serological, and molecular methods.

Case presentation
A 36-year-old Eritrean man who had lived in Denmark for the past 3 years presented to the hospital with 4 months’ history of abdominal pain, back pain, and weight loss of 12 kg. He underwent 18F-FDG-PET/CT scanning. The scan findings were consistent with schistosomiasis, which were confirmed by serological and pathological tests.

Conclusion
PET/CT is a common modality neither to detect schistosomes nor to diagnose schistosomiasis. A presumptive diagnosis can be made based on coincidence of high FDG uptake in visceral lymph nodes below the diaphragm and in relation to abdominal viscera, travel history suggestive of schistosome infection, and exclusion of other causes of abdominal pain.
Plasminogen activator inhibitor-1 gene polymorphism as a risk factor for vascular complications in type 2 diabetes mellitus
Authors: Khalaf Fatma A. , Ibrahim Hatem R. , Bedair Hanan M. , Allam Maha M. , Elshormilisy Amr A. , Ali Samia T. , Gaber Waseem M. 
Published: October 2019

AbstractBackgroundDiabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications. Other factors such as hypertension, obesity, and hyperlipidemia may worsen or accelerate the others. Several studies have revealed definitive genetic predispositions to the development of type 2 diabetes mellitus (T2DM) and development of vascular complications. This study aimed to address the association between plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and T2DM, and if this gene polymorphism may have a possible role in the development of vascular complications in T2DM. This study is a case control; it included 200 patients with T2DM, 117 patients had no vascular complications, and 83 had previous vascular complications (VCs). One hundred eighty volunteer blood donors were selected as a healthy control group. All patients and controls were subjected to clinical examination, and laboratory investigations included lipid profile, fasting and 2 h blood glucose, complete blood cell count,d-dimer, PAI-1, thrombin activatable fibrinolysis inhibitor (TAFI), and detection of PAI-1 gene polymorphism by real-time polymerase chain reaction (PCR).ResultsThe most prevalent genotype of PAI-1 gene polymorphism in all studied groups, including controls, was 4G/5G with the highest allele frequency as 4G. The 4G/5G and 4G/4G genotypes were associated with increased risk of DM development as compared to 5G/5G genotype. The 4G/5G and 4G/4G genotypes also had a highly significant increased risk of VCs among diabetic patients, as compared to 5G/5G. The 4G allele also was highly associated with DM with VCs. Thed-dimer TAFI, PAI-1 showed the highest levels in 4G/5G genotype followed by 4G/4G genotype. The lowest level was expressed in 5G/5G genotype in diabetic patients with and without VCs. The univariable analysis showed that genotypes 4G/5G and 4G/4G were potentially risk factors for development of VCs with T2DM patients.ConclusionThis study concludes that the PAI-1 4G/5G polymorphism may be associated with T2DM and may be considered as a risk factor for development of thrombotic events. It may also help in selection and dosing of patients being treated with anticoagulant and fibrinolytic agents. Further large-scale studies are recommended to assess the possible role of environmental factors and gene interactions in the development of T2DM vascular risks.