bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of in vivo nodal staging of solid malignancies with USPIO-enhanced MRI: a workflow protocol
Authors: Driessen Daphne A.J.J. , Gouw Didi J.J.M. de , Stijns Rutger C.H. , Litjens Geke , Israël Bas , Philips Bart W.J. , Hermans John J. , Dijkema Tim , Klarenbeek Bastiaan R. , Post Rachel S. van der , Nagtegaal Iris D. , Grunsven Adriana C.H. van Engen-van , Brosens Lodewijk A.A. , Veltien Andor , Zámecnik Patrik , Scheenen Tom W.J.
Published: September 2020

BackgroundIn various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology. MethodsIn patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious for harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla (T) preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR-images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens. ResultsMatching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology which allowed for analyses on nodal, or at least on nodal station level.ConclusionsA workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed analysis at nodal level, or at least nodal station level of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced MRI detected lymph nodes. Trial registrationVALINODE data is collected from patients undergoing USPIO-enhanced MRI in the clinical setting. Therefore, the trial has not been registered in an online trial register. 7TNANO1 is registered at Clinicaltrials.gov: NCT02751606, April 26 2016 (https://clinicaltrials.gov/ct2/show/NCT02751606). NANO-PANC is registered at Clinicaltrials.gov: NCT04311047, March 17 2020 (https://www.clinicaltrials.gov/ct2/show/NCT04311047). PRECIES is registered in the Dutch Trial Register: NTR6072, August 5 2016 (https://www.trialregister.nl/trial/5797). USPIO-NECK is registered at Clinicaltrials.gov: NCT03817307, January 25 2019 (https://clinicaltrials.gov/ct2/show/NCT03817307).
ZnT8 Loss-of-Function Accelerates Functional Maturation of hESC-Derived β Cells and Resists Metabolic Stress Induced Cell Death in Diabetes
Authors: Li Weida , Ma Qing , Xiao Yi-Ni , Li Sheng , Wang Menghan , Yang Zhihao , Xiao Tinghui , Xu Minglu , Zhang Tengjiao , Hu Rui , Zhang Zhen-Ning , He Qing , Su Qiang , Yuan Fei , Zhao jiaxu , Chen Zheng-Jun , Shi Weiyang , Deng Qiaolin , Cheng Xin
Published: September 2020

Human embryonic stem cells (hESCs) derived β cells (SC-β cells) hold great promise for diabetes treatment, yet how to achieve functional maturation of these SC-β cells and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remain elusive. By single cell RNA-seq pseudotime analysis, we revealed that ZnT8 is involved in SC-β cells functional maturation process and its loss of function (LOF) accelerates functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) and enhances proinsulin to insulin conversion efficiency in SC-β cells, both in vitro and in vivo, by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, SC-β cells with ZnT8 LOF are resistant to metabolic stresses induced cell death, as lipotoxicity or glucotoxicity, displaying higher survival. Most importantly, transplantation of SLC30A8-/- SC-β cells into diabetic mice significantly improves glycemia restoration and SC-β cell survival with long-term stability. Therefore, our study offers an advanced cell replacement therapy for diabetes with both improved SC-β cell survival and function against metabolic stress.
Visual Barcodes for Multiplexing Live Microscopy-Based Assays
Authors: Kaufman Tom , Nitzan Erez , Firestein Nir , Ginzberg Miriam , Iyengar Seshu , Patel Nish , Ben-Hamo Rotem , Porat Ziv , Hilfinger Andreas , Kafri Ran , Straussman Ravid
Published: September 2020

While multiplexing samples using DNA barcoding revolutionized the pace of biomedical discovery, multiplexing of live imaging-based applications has been limited by the number of fluorescent proteins that can be deconvoluted using common microscopy equipment. To address this limitation we developed visual barcodes that discriminate the clonal identity of single cells by targeting different fluorescent proteins to specific subcellular locations. We demonstrate that deconvolution of these barcodes is highly accurate and robust to many cellular perturbations. We then used visual barcodes to generate ‘Signalome’ cell-lines by multiplexing live reporters to monitor the simultaneous activity in 12 branches of signaling, in live cells, at single cell resolution, over time. Using the ‘Signalome’ we identified two distinct clusters of signaling pathways that balance growth and proliferation, emphasizing the importance of growth homeostasis as a central organizing principle in cancer signaling. The ability to multiplex samples in live imaging applications, both in vitro and in vivo may allow better high-content characterization of complex biological system
Influence of Pre-Plasma on Accelerated Protons in Ultraintense Laser Interaction with Not-So-Thin Foils
Authors: Gizzi Leonida , Boella Elisabetta , Labate Luca , Baffigi Federica , Bilbao Pablo , Brandi Fernando , Cristoforetti Gabriele , Fazzi Alberto , Fulgentini Lorenzo , Giove Dario , Koester Petra , Palla Daniele , Tomassini Paolo
Published: September 2020

We report on recent experimental results on proton acceleration from laser interaction with foil targets at ultra-relativistic intensities. We show a three-fold increase in the proton cut-off energy when a micrometer scale-length pre-plasma is introduced by irradiation with a low energy femtosecond pre-pulse. The foil target is sufficiently thick to prevent disruption of the sheath field at the rear surface by the shock launched by the pre-pulse. Measurements are compared with accurate, numerical hydrodynamic and Particle-In-Cell simulations where the role of the finite plasma scale-length at the laser-target interface is taken into account and the role of stochastic heating in enhancing fast electron production is discussed.
miR-125b-5p is A Promising Novel Plasma Biomarker for Alveolar Echinococcosis in Patients from the Southern Province of Qinghai
Authors: Cao Deping , Jiang Bofan , Zhang Yaogang , Pang Mingquan
Published: September 2020

Background: Alveolar echinococcosis is an infectious zoonotic disease caused by Echinococcus multilocularis that is endemic to the vast pastoral areas of southern Qinghai province of China. Alveolar echinococcosis affects the human liver, and its clinical manifestations are similar to those of liver tumors. It is also called “worm cancer,” as it induces irreversible liver fibrosis and brain metastases. Alveolar echinococcosis is a serious threat to human health and is a burden to patients and economies. When detected and treated early, patients with alveolar echinococcosis have a strong chance of recovery. Therefore, it is imperative to identify early diagnostic biomarkers of the disease. MicroRNAs (miRNAs) are short, single-stranded, non-coding RNA molecules that play key roles in a wide range of biological processes, and have been recently implicated in tumorigenesis. However, little is known about the role of miRNAs in alveolar echinococcosis. We have previously reported differentially expressed miRNAs in the plasma of patients with alveolar echinococcosis and healthy individuals, using microarray assay chips. Methods: We screened 10 differentially expressed miRNAs based on their fold change and the available literature. Additionally, quantitative polymerase chain reaction was used to verify their expression in the plasma of alveolar echinococcosis patients. We found that hsa-miR-125b-5p was upregulated in the plasma and the hepatic tissue samples of alveolar echinococcosis patients; therefore, its role as a diagnostic biomarker for alveolar echinococcosis was investigated. Accordingly, hsa-miR-125b-5p was upregulated in plasma and hepatic tissue samples obtained from alveolar echinococcosis patients. Receiver operating characteristic curves showed that hsa-miR-125b-5p was associated with an area under the curve of 99.8% and 98.9% in the plasma and hepatic tissues of alveolar echinococcosis patients, respectively. Transfection of an LV-hsa-miR-125b-5p-inhibitor reduced apoptosis of L-O2 hepatocytes in vitro (P < 0.05). Thus, hsa-miR-125b-5p may promote liver cell proliferation and inhibit liver cell apoptosis.Conclusions: Taken together, hsa-miR-125b-5p may be a promising diagnostic biomarker for the early non-invasive diagnosis of alveolar echinococcosis. We plan to validate the expression of hsa-miR-125b-5p in the plasma of patients with cystic echinococcosis, alveolar echinococcosis, and other liver diseases to determine the potential of hsa-miR-125-5p as a differential biomarker in future studies.
Special Pathologic Features of Adolescent Idiopathic Scoliosis: Could There be a New Type of Muscular Dystrophinopathy?
Authors: Zheng Danfeng , Li Junyu , Li Jiaxi , Zhang Yingshuang , Yu Miao
Published: September 2020

Background: Adolescent idiopathic scoliosis (AIS) is characterized by vertebral rotation and lateral curvature of the spine and affects 2-4% of the population throughout the world and the cause of the disease is still controversial. Recent researches suggest that there is an internal correlation between certain neuromuscular diseases and AIS. This study aims to characterize the paraspinal muscles of AIS patients, and to further explore the its etiology.Methods: Eighteen AIS patients treated with posterior scoliosis correction surgery were included and had biopsies taken from the paraspinal muscle at the apex vertebra region. Serial sections with conventional H&E staining and histochemical staining were obtained, and immunohistochemical examinations were employed to detect Dystrophin-1, -2, -3, Myosin, MHC-1, CD4, CD8, CD20, and CD68 or CD163 antibodies. Biopsy samples were grouped according to the subjects’ Cobb angle and Nash-Moe’s classification respectively, and the corresponding pathological changes were compared between groups. Results: The immunohistochemical staining results showed significant differences in the expression pattern of Dystrophin-2 (P=0.023) and Dystrophin-total (P=0.018) between the mild and severe scoliosis groups, with the expression of Dystrophin more abnormal or absent in the severe scoliosis group. There were also significant differences in the expression pattern of Dystrophin-2 (P=0.035) between the Nash-Moe classification subgroups. The expression of Dystrophin-3 was absent to various extent in all patients. Besides, we observed an infiltration of CD4+ and CD8+ cells in the paraspinal muscles and tendons. In all patients, the expression of MHC-1 on myolemma was present in some muscle fibers.Conclusions: The expression of dystrophin protein was significantly reduced and was correlated with the severity of scoliosis, suggesting that dystrophin protein dysfunctions contribute to the development of scoliosis. Meanwhile, the inflammatory changes of AIS mainly manifested in T cell activation and infiltration, and there seemed to be certain correlations between the expression of MHC-1 and the abnormal expression of dystrophin protein. Further studies along these results may open up new ideas for the diagnosis of scoliosis and the treatment for paraspinal myopathy.
Defining the Role of TT-TG and TT-PCL in the Diagnosis of Lateralization of the Tibial Tubercle in Recurrent Patellar Dislocation
Authors: su peng , jian nengri , Mao Beini , zhang zhong , Li Jian , FU Weili
Published: September 2020

BackgroundThe radiological indicators can help doctors determine whether to make the tibial tubercle transfer. But that which indicator is better is still in question.Methods117 knees in 103 patients who had gone through patellar surgery and 60 knees in 58 patients who had no history of patellar dislocation from 2014 to 2019 were analyzed. Significant differences of tibial tubercle–trochlear groove (TT-TG) on CT and tibial tubercle–posterior cruciate ligament (TT-PCL) on MRI between the case group and the control group were estimated by an unpaired t test. Significant differences between TT-TG on CT and TT-TG on MRI were estimated by a paired t test. The correlation between TT-PCL on MRI and tibial width was estimated by Pearson test. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were measured to assess the diagnostic accuracy of TT-TG and TT-PCL on MRI. ResultsThe intraclass correlation coefficient (ICC) for inter-method of TT-TG evaluated by two raters was were 0.566. When comparing TT-TG on CT with that on MRI, the mean difference was 2.5mm (p<0.001). The mean TT-TG difference on CT between the case group and the control group was 5.3 mm, which was significantly bigger than the mean TT-PCL difference on MRI of 1.2mm(p<0.001). AUC of TT-TG on CT and TT-PCL were 0.838 and 0.580 (P<0.001). TT-PCL correlated with tibial width (r=0.450, P<0.001). Conclusion﻿A statistically significance and a fair ICC proved that TT-TG could not be used interchangeably. The bigger mean difference between the case group and the control group and better AUC proved that TT-TG on CT might be an indicator more suitable for measuring the lateralization of the tibial tubercle. And TT-TG should be considered as an individual parameter because of the significant correlation with tibial width.
Live Birth Rate of Fresh Embryo Transfer with GnRH Agonist Long Protocol is Higher Than Frozen Embryo Transfer
Authors: Ding Xiaoyan , Yang Jingwei , Li Lan , Yang Na , Lan Ling , Huang Guoning , Ye Hong
Published: September 2020

Background: Along with progress in embryo cryopreservation, especially in vitrification has made freeze all strategy more acceptable. Some studies found comparable or higher live birth rate with frozen embryo transfer (FET) than with fresh embryo transfer（ET）in gonadotropin releasing hormone antagonist (GnRH-ant) protocol. But there were no reports about live birth rate differences between fresh ET and FET with gonadotropin releasing hormone agonist (GnRH-a) long protocol. The aim of this study is to analyze whether patients benefit from freeze all strategy in GnRH-a protocol from real-world data.Methods: This is a retrospective cohort study, in which women undergoing fresh ET or FET with GnRH-a long protocol at Chongqing Reproductive and Genetics Institute from January 2016 to December 2018 were evaluated. The primary outcome was live birth rate. The secondary outcomes were implantation rate, clinical pregnancy rate, pregnancy loss and ectopic pregnancy rate.Results: A total of 7,814 patients met inclusion criteria, implementing 5,216 fresh ET cycles and 2,598 FET cycles, respectively. The demographic characteristics of the patients were significantly different between two groups, except BMI. After controlling for a broad range of potential confounders (including age, infertility duration, BMI, AMH, no. of oocytes retrieved and no. of available embryos), multivariate logistic regression analysis demonstrated that there was no significant difference in terms of clinical pregnancy rate, ectopic pregnancy rate and pregnancy loss rate between two groups (all P>0.05). However, the implantation rate and live birth rate of fresh ET group were significantly higher than FET group (P<0.001 and P=0.012, respectively).Conclusion: Compared to FET, fresh ET following GnRH-a long protocol could lead to higher implantation rate and live birth rate in infertile patients underwent in vitro fertilization (IVF). The freeze all strategy should be individualized and made with caution especially with GnRH-a long protocol.
Selonsertib, a Potential Drug for Liver Failure Therapy by Rescuing the Mitochondrial Dysfunction of Macrophage via ASK1-JNK-DRP1 Pathway
Authors: Lou Guohua , Li Aichun , Zhang Tianbao , Qi Jinjin , Chen Zhi , Liu Yanning
Published: September 2020

BackgroundAcute liver failure (ALF) is associated with high mortality rate and there are still no effective treatments expect liver transplantation and artificial liver therapies. This study was aimed to determine the effects, therapeutic window and mechanisms of selonsertib, a selective inhibitor of ASK1, for ALF therapy.ResultsLipopolysaccharide and D-galactosamine (LPS/GalN) was used to simulate ALF. We found that selonsertib pretreatment significantly ameliorated ALF as determined by reduced hepatic necrosis and serum alanine aminotransferase, aspartate aminotransferase and inflammatory cytokine levels. However, selonsertib is only effective early after LPS/GalN administration and the limited therapeutic window was related to the activation and mitochondrial translocation of JNK and DRP1. Further experiments revealed that selonsertib could alleviate LPS-induced mitochondrial damage in macrophages by evaluating the mitochondrial membrane potential and mitochondrial permeability transition pore opening in macrophages. Selonsertib also suppressed the release of inflammatory cytokines from macrophages by reducing DRP1-mediated mitochondrial dysfunction, which was confirmed by using mdivi, the specific DRP1 inhibitor.ConclusionsSelonsertib protected against LPS/GalN-induced ALF by attenuating JNK-mediated DRP1 mitochondrial translocation and then rescuing mitochondrial damage in macrophages and may have therapeutic potential for early ALF patients.
Elderly patients of mild cognitive impairment exhibit altered profiles of the gut microbiota
Authors: Pan Qiong , Li Ya-Qian , Guo Ke , Xue Min , Gan Yu , Wang Kejian , Xu Da-Bao , Tu Qiu-Yun
Published: September 2020

Background
As the transitional state between normal aging and Alzheimer’s disease (AD), mild cognitive impairment (MCI) is characterized by cognitive decline greater than natural aging. While the association between AD and gut microbiota has been reported in a number of studies, there is still very limited microbial research about MCI.
Methods
Here we enrolled 48 participants, including 22 MCI cases and 26 normal controls. Fecal samples were collected for 16S rRNA quantitative arrays and bioinformatics analysis.
Results
Both Principal Coordinates Analysis (PCoA) and Non-metric Multidimensional scaling (NMDS) demonstrated that the microbial composition of MCI individuals deviated from the cluster of healthy controls. Multiple bacterial species were significantly increased (e.g., Staphylococcus intermedius) or decreased (e.g., Bacteroides salyersiae) in the samples from MCI group.
Conclusion
Therefore, the composition of gut microbiota differed between control subjects and MCI cases. Our study is the first to identify a series of MCI signature species in the gut microbiota, thus providing a new direction for future development of early diagnosis and probiotics regimen.
Nanoparticles of Conformation-stabilized Canine Distemper Virus Hemagglutinin are Highly Immunogenic and Induce Robust Immunity
Authors: Feng Hao , Dong Jingjian , Chen Yan , Shi Lili , Shen Bing , Sun Xianliang , Xia Xianzhu , Feng Na
Published: September 2020

BackgroundCanine distemper virus (CDV) infection of ferrets, dogs, and giant pandas causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system. In this study, we tested a new type candidate CDV vaccine–CDV nanoparticles–based on hemagglutinin protein. MethodsThe nanoparticles were generated from conformation-stabilized CDV hemagglutinin tetramers. Immune responses against CDV were evaluated in mice. Immunization was initiated 6 weeks after birth and boosted twice with 4-week intervals. The blood and mucosal samples were collected 2 weeks after each immunization. ResultsVaccination with CDV nanoparticles elicited high levels of IgG antibody titers in mice (approximately seven- to eight fold higher than that obtained with soluble CDV H protein), as well as mucosal immune responses, and developed increased CDV-specific neutralizing antibody. The mice that received nanoparticles showed significantly higher IFN-γ- and IL-4-secreting cell population in the spleen and lymph node compared with mice immunized with soluble H protein. The co-stimulatory molecular expression of CD80 and CD86 on the surface of DCs were also upregulated. ConclusionThe results demonstrate that self-assembly into nanoparticles can increase the immunogenicity of vaccine antigens, and nanoparticles assembled from conformation-stabilized CDV H protein has the potential to serve as a new type CDV vaccine.
Quality Evaluation of Clinical Practice Guidelines for Comprehensive Patient Assessment in Emergency Care: A National Cross-sectional Survey
Authors: Falchenberg Åsa , Andersson Ulf , Sundström Birgitta Wireklint , Bremer Anders , Andersson Henrik
Published: September 2020

Background Clinical practice guidelines (CPGs) provide guidance for emergency care clinicians to perform patient assessments. Neglecting CPGs may lead to incomplete or fragmented assessments and cause ad-verse events. However, it is important for CPGs to be evidence based, and patient assessments must be conducted in such a manner that high levels of patient safety can be achieved. The aim of this study was to explore and evaluate the quality of emergency medical services (EMS) and emer-gency departments (EDs) CPGs for comprehensive patient assessments. Methods A national cross-sectional design was used, and the listed managers from 97 organizations (25 EMS and 72 EDs) were contacted, covering all 20 Swedish county councils. Fifteen guidelines were ap-praised using the validated Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool. Results The results revealed that none of the CPGs outlined a comprehensive patient assessment. The main characteristic of the CPGs was their focus on the medical assessment of patients with life-threatening conditions, mostly based on initial assessment and the A-E principle (airway, breathing, circulation, disability, and exposure). According to the AGREE II analysis, the overall quality of the guidelines was poor. CPGs lacked scientific support, underlying evidence, descriptions of how that evidence was collected, and explanations of the criteria used for CPG development. Conclusions This research indicated that there were no Swedish CPGs with comprehensive patient assessments in emergency care and that the foundation for evidence-based CPGs for comprehensive patient assessments was weak.
Knowledge About Leprosy Among Health Care Workers In Balaka District, Southern Malawi
Authors: Mponda Kelvin , Anafi George , Laja Eric Thom , Chidothe Rapson , Mahuka Lawrence , Duncan Ephraim , Ng’oma David , Hees Colette van
Published: September 2020

Background

Health care workers (HCW) who are knowledgeable about leprosy can play an important role in promoting early case detection to prevent disabilities. Poor knowledge of leprosy leads to poor attitude about the disease and towards its sufferers. This study was done to assess knowledge and attitudes of health workers towards leprosy in Balaka district, southern Malawi.
Methods

This was a cross sectional study that included all HCW that do outpatient consultations in health facilities in Balaka district using a self-administered questionnaire. Statistical Package for the Social Sciences (SPSS) version 20 was used for analysis.
Results

Thirty five of the approached 38 HCW had heard about leprosy (21 nurses, 3 health surveillance assistants and 11 medical assistants). While 21 (60%) reported to ever have suspected leprosy in a patient, 13 (37%) HCW had never seen a case of leprosy before and 6 HCW (17%) had ever made a correct diagnosis of leprosy themselves. Twenty nine (83%) knew leprosy is an infectious disease, 1 (2.9%) thought it is due to witchcraft, 2 (5.7%) thought dirty environment causes leprosy. Six HCW (17%)mentioned inhalation as mode of transmission, 19 (54%) thought touching someone with the disease, 4 (11%) eating infected meat and another 4 (11%) uncleanliness can transmit leprosy. The skin and peripheral nerves were correctly mentioned by 32 HCW (91%) as organs which may be affected by leprosy. Whether leprosy is curable, 25 (71%) thought it is, 5 (14%) thought it is incurable and another 5 (14%) did not know. Seventeen HCW (49%) felt leprosy patients need isolation and 19 HCW (54%) were afraid they might catch leprosy at work. Of three diseases leprosy, HIV and diabetes, 26 (74%) HCW felt leprosy was the most dangerous as opposed to 4 (11%) and 3 (9%) that chose HIV and diabetes respectively. Only (16) 46% had learnt about leprosy during their training but 24 (69%) had read about leprosy out of self-interest and all the HCW felt they need on job or refresher training about leprosy.
Conclusion

There is a general lack of knowledge about leprosy. This may explain why many HCW have not had experience with leprosy patients even though it exists in their areas. Their fears about leprosy infectiousness and dangerousness are also based on this knowledge lack. Since such poor knowledge may lead to delayed diagnosis and stigma, education about leprosy to HCWs in Balaka must be part of any priority interventions to address challenges with leprosy control in the district.
Genomic analysis reveals independent evolution of Plasmodium falciparum population in Ethiopia
Authors: Abera Deriba , Kibet Caleb Kipkurui , Degefa Teshome , Amenga-Etego Lucas , Bargul Joel L , Golassa Lemu
Published: September 2020

Background
Plasmodium falciparum parasite populations have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there was paucity of data on the genomic characterization and the evolutionary adaptations of P. falciparum isolates from central area of Ethiopia.
Method
: Whole genome analysis of 25 P. falciparum isolates from central Ethiopia were made to determine their genetic diversity, population structures and signatures of selection in known drug resistance loci against isolates from Cambodia, Thailand, DR Congo and Malawi.
Result
A total of 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified with average nucleotide diversity (π = 0.00022) across the genome. About 84% of the Ethiopian P. falciparum isolates had FWS value > 0.95 showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areas with low transmission intensity. Within host diversity of Ethiopian infections was significantly different from East African (p < 0.001) but not Southeast Asian infections (P > 0.05). A significant population structure differentiation between Ethiopian parasites and East Africa (Fst < 10%) and Southeast Asia populations (Fst ~ 18%) has been observed, suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, a total of 125 genes under balancing selection is identified that included ama1, trap, eba175, and lsa3 previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the pfcrt, pfdhfr, pfdhps, pfmdr1, and pfK13 genes. However, mutations analysis showed that at least one SNP marker was fixed in these genes, but not in pfdhps and pfK13.
Conclusion
Plasmodium falciparum population in central region of Ethiopia were structurally diverged from both southeast Asian and other East African populations. A low within host diversity is noted among the Ethiopian parasites. Indeed, the parasites carry fixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.
Use of the Creating Opportunities for Parent Empowerment Program to Decrease Mental Health Problems in Ugandan Children Surviving Severe Malaria: A Randomized Controlled Trial
Authors: Bangirana Paul , Birabwa Annet , Nyakato Mary , Nakitende Ann J. , Kroupina Maria , Nakasujja Noeline , Musisi Seggane , John Chandy C. , Idro Richard
Published: September 2020

Background: Severe malaria is associated with long-term mental health problems in Ugandan children. This study investigated the effect of a behavioral intervention for caregivers of children admitted with severe malaria, on the children’s mental health outcomes six months after discharge.Methods: This randomized controlled trial was conducted at Naguru Hospital in Kampala, Uganda from January 2018 to July 2019. Caregiver and child dyads were randomly assigned to either a psychoeducation arm providing information about hospital procedures during admission (control group) or a behavioral arm providing information about the child’s possible emotions and behavior during and after admission and providing age appropriate games for the caregiver and child (intervention group). Pre- and post-intervention assessments for caregiver anxiety and depression (Hopkins Symptom Checklist) and child mental health problems (Strength and Difficulties Questionnaire and the Child Behavioral Checklist) were done during admission and six months after discharge respectively. T-tests, analysis of covariance and Chi-Square were used to compare outcomes between the two treatment arms.Results: There were 120 caregiver-child dyads recruited at baseline with children aged 1.45 years to 4.89 years (mean age 2.85 years, SD = 1.01). The intervention and control groups had similar sociodemographic, clinical and behavioral characteristics at baseline. Caregiver depression at baseline, mother’s education and female sex of the child were associated with behavioral problems in the child at baseline (p<0.05). At six months follow-up, there was no difference in the frequency of behavioral problems between the groups (6.8% vs 10% in intervention vs. control groups, respectively, p = 0.72). Caregiver depression and anxiety scores between the treatment arms did not differ at six months follow-up. Conclusion: This behavioral intervention for caregivers and their children admitted with severe malaria had no effect on the child’s mental health outcomes at six months. Further studies need to develop interventions for mental health problems after severe malaria in children with longer follow-up time.ClinicalTrials.gov Identifier: NCT03432039
Derivation and Validation of the ED-SAS Score for Very Early Prediction of Mortality and Morbidity with Acute Pancreatitis: A Retrospective Observational Study
Authors: Miller Joseph , Wu Yiyang , Safa Rawan , Marusca Georgiana , Bhatti Sandeep , Ahluwalia Guneet , Dandashi Jad , Acevedo Harold Gomez , Farook Naureen , Scott Ashley , Nair Vidhya , Adhami Angie , Dueweke Jeffrey , Hebbar Sudarshan , Ekstrom Leeland
Published: September 2020

Background: Existing scoring systems to predict mortality in acute pancreatitis may not be directly applicable to the emergency department (ED). The objective of this study was to derive and validate the ED-SAS, a simple scoring score using variables readily available in the ED to predict mortality in patients with acute pancreatitis. Methods: This retrospective observational study was performed based on patient level data collected from electronic health records across 2 independent health systems, one used for the derivation cohort and one for the validation cohort. Adult patients who were eligible presented to the ED, required hospital admission, and had a confirmed diagnosis of acute pancreatitis. Patients with chronic or recurrent episodes of pancreatitis were excluded. The primary outcome was 30-day mortality. Analyses tested and derived candidate variables to establish a prediction score and that was subsequently applied to the validation cohort to assess odds ratio for the primary and secondary outcomes. Results: The derivation cohort included 599 patients, and the validation cohort 2011 patients. Thirty-day mortality was 4.2% and 3.9% respectively. From the derivation cohort, 3 variables were established for use in the predictive scoring score: ≥2 systemic inflammatory response syndrome (SIRS) criteria, age >60 years, and SpO2 <96%. Summing the presence or absence of each variable yielded an ED-SAS score ranging from 0 to 3. In the validation cohort, the odds of 30-day mortality increased with each subsequent ED-SAS point: 4.4 (95% CI 1.8 – 10.8) for 1 point, 12.0 (95% CI 4.9 – 29.4) for 2 points, and 41.7 (95% CI 15.8 – 110.1) for 3 points (c-statistic = 0.77).Conclusion: An ED-SAS score that incorporates SpO2, age, and SIRS measurements provides a rapid method for predicting 30-day mortality in acute pancreatitis.
Bioinformatic Analysis Reveals VEGFA Promotes the Occurrence of PLA2R-associated Idiopathic Membranous Nephropathy by Angiogenesis via PI3K/AKT Signaling Pathway
Authors: Ke Ben , Shen Wen , Duan Zhibing
Published: September 2020

Backround: PLA2R-associated IMN covers 70% of IMN, which is one of the main types of chronic kidney disease in adults and one of the most common causes of end‑stage renal disease. Vascular endothelial growth factor A (VEGFA), a homodimeric vasoactive glycoprotein, is the key mediator of angiogenesis, which lead to numerous kidney diseases, including TSHD7A-associated IMN. However, the role of VEGFA in PLA2R-associated IMN is still poorly understood.Methods: We downloaded the microarray data GSE115857 from GEO. The DEGs were identified with R software, and the functional and pathway enrichment analysis of DEGs was performed utilizing the DAVID and Cytoscape ClueGo plug-in. A comprehensive list of interacting DEGs was constructed using the STRING database and visualized by Cytoscape software. The Cytoscape MCODE and cytoHubba plug-in were used to identify clustered sub-networks, and hub genes from the protein-protein interaction network. Gene set enrichment analysis (GSEA) was used to identify signaling pathway in IMN. Results: There were 1422 genes (952 up-regulated genes and 470 down-regulated genes) were identified as DEGs in GSE115857. The BP of DEGs in GSE115857 was clustered in regulation of transcription from RNA polymerase II promoter, positive regulation of nuclear-transcribed mRNA poly(A) tail shortening, cell adhesion et al. The KEGG pathway of DEGs in GSE115857 was clustered in Rheumatoid arthritis, ABC transporters, PI3K/AKT signaling pathway et al. Then we got a huge PPI network from STRING. 6 modules were screen out to study the functional changes in IMN. The KEGG pathway of module 3 was enriched in soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) interactions in vesicular transport. There were 3 hub genes screened out, namely, VEGFA, JUN,and FOS. Following the random walk, all genes were ranked and GSEA analysis showed that the signaling pathway of DEGs in GSE115857 was focused on angiogenesis, in which VEGFA acts as a core gene. CONCLUSION: In summary, this study reveals VEGFA promotes PLA2R-associated IMN by stimulating angiogenesis via PI3K/AKT signaling. Moreover, SNARE interactions in vesicular transport was involved in the development of PLA2R-associated IMN, which may offer a novel therapeutic strategy in treatment of IMN.
Therapeutic Prediction of HIV-1 DNA Decay: A Multicenter Longitudinal Cohort Study
Authors: Yue Yongsong , Li Yijia , Cui Yizhi , Wang Nidan , Huang Yunda , Cao Wei , Han Yang , Zhu Ting , Lyu Wei , Xie Jing , Song Xiaojing , Li Yanling , Wang Tong , Zhu Tuofu , Li Taisheng
Published: September 2020

Background: Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions.Methods: Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, and 288 weeks after combined antiretroviral therapy (cART) initiation in 607 treatment-naïve patients with chronic HIV-1 infection were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART.Results: The total HIV-1 DNA rapidly decreased from baseline [mean = 3.04 log10 copies/106 peripheral blood mononuclear cells (PBMCs)] to week 24 (mean = 2.51 log10 copies/106 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (<100 copies/106 PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log10 copies/106 PBMCs, P < 0.001] and higher baseline CD4+ T cell count (RR = 1.72, per 100 cells/μL, P < 0.001) were significantly associated with a low total HIV-1 DNA count at week 96. In an independent cohort of 117 patients, this model achieved a sensitivity of 75.00% and specificity of 69.52%.Conclusions: The derived model based on baseline total HIV-1 DNA and CD4+ T cell count provides a useful prognostic tool in predicting HIV-1 DNA reservoir control during cART.
Effect and Mechanisms of Reproductive Tract Infection on Oxidative Stress Parameters, Sperm Dna Fragmentation, and Semen Quality in Infertile Males
Authors: Liu KangSheng , Mao Xiao-Dong , Pan Feng , Yang Xinyuan
Published: September 2020

Recent years have seen a rise incidence of male infertility, and mostly caused by the decline of sperm quality. The ratio of infertile males to infertile females has escalated from 3:7 in 2013 to today’s 5:5, which turning male infertility into the research focus of reproductive medicine. This study aimed to clarify the effect of reproductive tract infection by ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) on the DNA integrity and routine semen parameters of infertile males. A retrospective study was performed. A total of 259 infertile males who were treated at the Andrological Laboratory Examination and Reproductive Medicine Center in our hospital were analyzed. qRT-PCR was used to examine the infection status of CT and UU. According to the eligibility criteria, we evaluated the semen parameters and biochemical data of 253 men. Based on the results of PCR, the subjects were divided into four groups: group I (CT positive, 63 cases), group II (UU positive, 60 cases), group III (CT positive and UU positive, 62 cases), and group IV (no infection, 68 cases). DNA fragmentation index (DFI), sperm count, vitality and morphology, elastinase level, seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) were assessed. Compared to group IV, three groups (group I, group II and group III) showed difference in semen volume, proportion of sperm with normal morphology, sperm motility, progressive motility, and vitality (P<0.05). Compared to group IV, group II and group III showed difference in DFI (P<0.05). Compared to group IV, group II and group III showed difference in elastase level (P<0.05). VCL, VSL, VAP, WOB,ROS,TM, HDS showed differences between groups of abnormal/normal WBC (*P<0.01) UU infection significantly increased the level of seminal leukocytes only in group II, but not in the other three groups, indicating that UU is an factor to increase the level of seminal leukocytes. Compared with the normal leukocyte group, there were significant differences in total motility, forward motility and normal sperm ratio between the two groups. The proportion of sperm with abnormal morphology (mostly in the head) showed obvious difference between groups of high and normal seminal leukocytic level. At the same time, in this study, SCGE and SCD verified that leukocytes could damage sperm DNA by increasing ROS, which ultimately affects male fertility.
Induced Hyperglycemia in Mice is Controlled Following the Microfluidic System- Assisted Transplantation of Stem Cells-derived Insulin-producing Cells Transduced with miRNA
Authors: Soltani Adele , Soleimani Masoud , Ghiass Mohammad Adel , Enderami Seyed Ehsan , Rabbani Shahram , Jafarian Arefeh , Allameh Abdolamir
Published: September 2020

BackgroundCell-based therapy is a promising approach for the treatment of type 1 diabetes mellitus. Identification of stem cells as progenitor stem cells with differentiation potential to Insulin-producing cells (IPCs) and their application is an emerging issue. Different strategies have been used to support the cell survival and their specific functions to control hyperglycemia condition. Novel technology systems using appropriate materials/fibres can improve the cell transplantation.MethodsIn the present study, glucose-sensitive insulin-producing cells (IPCs) were differentiated from adipose-derived stem cells (ADSCs) transduced with miR-375 and anti-miR-7 to enhance the functions of the cells. The survival rate of the cells was also improved by using a microfluidic system prior to in vivo transplantation of the IPCs. The contribution of miR-375 with the anti-miR-7 in mature IPCs derived from ADSCs resulted in gaining the function of the cells as judged by insulin productionResultsAfter adopting a stable functional condition of the IPCs, the cells were used for in vivo grafting to diabetic mice which resulted in a substantial drop (5-folds) in blood glucose during four weeks of grafting. The pattern of blood glucose levels in the mice receiving fiber entrapped IPCs was similar to that of non-diabetic mice and blood glucose declined in animals treated with fiber-entrapped-IPCs. Blood insulin was elevated (2-folds) in diabetic mice received transplant of fiber-entrapped-IPCs carrying miR-375 and anti-miR-7 after five weeks of transplantation when compared to the untreated diabetic mice. For the first time, this study showed that the two-component microfluidic system is useful for supporting the Collagen-Alginate fiber-entrapped IPCs and the miRNAs-based cell therapy.ConclusionsOverall data show that the IPCs encapsulation by the microfluidic system can support the cells in terms of morphology and biological function and their efficiency for controlling the hyperglycemia condition in diabetic mice.
The Impact of Common Chronic Conditions on Health-Related Quality of Life: A General Population Survey in Iran Using EQ-5D-5L
Authors: Sari Ali Akbari , Karimi Fereshte , Emrani Zahra , Zeraati Hojjat , Olyaeemanesh Alireza , Daroudi Rajabali
Published: September 2020

Background:Diseases have undeniable effects on Health-Related Quality of Life (HRQoL). Chronic diseases, in particular, limit the productive potentials and HRQoL of individuals. EQ-5D is a very popular generic instrument, which can be used to estimate HRQoL scores in any diseases. The current study investigates mean HRQoL scores in certain chronic diseases and examines the relationship between utility scores and chronic diseases in Iran. Method:This cross-sectional study was carried out among the general adult population of Tehran. 3060 individuals were chosen by a stratified probability sampling method. The EQ-5D-5L questionnaire was applied. The utility scores were estimated using the Iranian crosswalk-based value set. The effect of chronic diseases on the HRQoL scores was derived by the Ordinary Least Squares (OLS) method. Data was analyzed using Stata version 13 software.Results:The mean ± standard deviation utility and EQ-VAS scores were 0.86 ±0.14 and 77.50 ±16.14 in the participants without any chronic conditions. The scores were 0.69 ±0.17 and 61.61 ±20.39 in the participants with chronic conditions. The highest and lowest mean utility scores were related to thyroid disease (0.70) and Stroke (0.54), respectively. Common chronic conditions had significant negative effects on the HRQoL scores. Stroke (0.204) and cancer (0.177) caused the most reduction in the EQ-5D-5L utility scores. Lumbar disc hernia, digestive diseases, osteoarthritis, breathing problems, and anxiety/nerves cause 0.133, 0.109, 0.108, 0.087, and 0.078 reductions, respectively, in the EQ-5D-5L utility scores.Conclusion:This study provides insight into some common chronic conditions and their effects on the HRQoL. Policymakers and planners should pay attention to the effects of chronic conditions especially high prevalence one. They should adopt effective interventions to control this issue and increase health. The results of this study can also be beneficial in economic evaluation studies.
Quantitative Imagery Analysis of Spot Patterns for Haplogroup Classification of Triatoma Dimidiata (Latreille, 1811) (Hemiptera: Reduviidae) an Important Vector of Chagas Disease
Authors: Flores Daryl David Cruz , Ávila Dennis Denis , Arellano Elizabeth , Ibarra-Cerdeña Carlos N.
Published: September 2020

Background: Spots and coloring patterns evaluated quantitatively can be used to discrimination and identify possible cryptic species. Triatoma dimidiata (Reduviidae: Triatominae) is one of the main complexes of Chagas disease vector species. Phylogenetic studies have defined three haplogroups for Mexico and part of Central America. In this work, we evaluate the possibility of correctly discriminating among these T. dimidiata haplogroups using the pattern of dorsal spots.Methods: Digital images of the dorsal region of individuals from the three haplogroups were used. We used image processing to extract primary and secondary variables characterizing the dorsal spot pattern. The statistical analysis of the variables included descriptive statistics, non-parametric Kruskal-Wallis tests, Discriminant Function Analysis (DFA), and a neural classification network.Results: A distinctive spot pattern was found for each haplogroup. The most differentiated pattern was presented by haplogroup 2, mainly apparent in the notably larger central spots. Haplogroups 1 and 3 were more similar to each other, but there were consistent differences in the shape and orientation of the spots. Significant differences were found among haplogroups in almost all the variables analyzed, these differences being greater in relative spot area, mean relative area of central spots, central spots Feret diameters, lateral spots Feret diameters and aspect ratio. Both the DFA and the neural network had correct discrimination values above 90%. Conclusions: We conclude that the spot pattern can be reliably used to discriminate among haplogroups, and possibly among triatomine species.