bluuebunny/crossref_metadata_2025 huggingface dataset:
Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Authors: Jadhav Vaishnavi S. , Lin Peter BC. , Pennington Taylor , Prisco Gonzalo Viana Di , Jannu Asha Jacob , Xu Guixiang , Moutinho Miguel , Zhang Jie , Atwood Brady K. , Puntambekar Shweta S. , Bissel Stephanie J. , Oblak Adrian L. , Landreth Gary E. , Lamb Bruce T
Published: September 2020

Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in the brain exclusively on microglia and genetic variants are linked to neurodegenerative diseases including Alzheimer’s disease (AD), frontotemporal dementia (FTD) and Nasu Hakola Disease (NHD). The Trem2 variant R47H, confers substantially elevated risk of developing late onset Alzheimer’s disease, while NHD-linked Trem2 variants like Y38C, are associated with development of early onset dementia with white matter pathology. However, it is not known how these Trem2 species, predisposes individuals to presenile dementia.Methods: To investigate if Trem2 Y38C or loss of Trem2 alters neuronal function we generated a novel mouse model to introduce the NHD Trem2 Y38C variant in murine Trem2 using CRISPR/Cas9 technology. Trem2Y38C/Y38C and Trem2-/- mice were assessed for Trem2 expression, differentially expressed genes, synaptic protein levels and synaptic plasticity using biochemical, electrophysiological and transcriptomic approaches.Results: While mice harboring the Trem2 Y38C exhibited normal expression levels of TREM2, the pathological outcomes phenocopied Trem2-/- mice at 6 months. Transcriptomic analysis revealed altered expression of neuronal and oligodendrocytes/myelin genes. We observed regional decreases in synaptic protein levels, with the most affected synapses in the hippocampus. These alterations were associated with reduced synaptic plasticity. Conclusion: Our findings provide in vivo evidence that Trem2 Y38C disrupts normal TREM2 functions. Trem2Y38C/Y38C and Trem2-/- mice demonstrated altered gene expression, changes in microglia morphology, loss of synaptic proteins and reduced hippocampal synaptic plasticity at 6 months in absence of any pathological triggers like amyloid. This suggests TREM2 impacts neuronal functions providing molecular insights on the predisposition of individuals with TREM2 variants resulting in presenile dementia.
Clinical characteristics of Epstein–Barrvirus infection in the pediatric nervous system
Authors: Cheng Huan , Chen DouDou , Peng XiaoLing , wu Peng , Jang Li , Hu Yue
Published: September 2020

Background: To investigate the clinical characteristics of Epstein–Barr virus (EBV) infection in the pediatric nervous system (NS). Methods: We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children's hospital of Chongqing Medical University from January 2008 to April 2019. Results: EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0–4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain–Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV. Conclusion: There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.
Development and Validation of a Nomogram Based on CA125 Levels for Predicting Progression-Free Survival in Patients with Ovarian Cancer
Authors: He Minjun , Xie Chuanbo , Huang Jun , Wei Wei , Wang Yin , lan chunyan
Published: September 2020

Background We aimed to develop and validate a nomogram incorporating CA125 levels after three cycles of chemotherapy for predicting progression-free survival (PFS) in patients with ovarian cancer.Methods The nomogram was developed in a primary cohort of 491 patients with stage II-IV ovarian cancer. Performance was assessed by concordance index (C-index), calibration curve, and decision curve analysis, and compared with the International Federation of Gynecology and Obstetrics (FIGO) staging system. The predictive value of CA125 levels after three cycles of chemotherapy was evaluated. The model was subjected to bootstrap internal validation. An independent cohort of 81 patients was used for external validation.Results CA125 levels after three cycles of chemotherapy were significantly associated with PFS. Five variables, including CA125 levels were selected to develop the nomogram. The nomogram demonstrated adequate discrimination, with a bootstrap-corrected C-index of 0.708, and good calibration. External validation of the nomogram achieved excellent discrimination (C-index, 0.724) and calibration. CA125 levels after three adjuvant chemotherapy cycles showed a marginally significant increment of discrimination to the nomogram in the primary cohort (C-index, 0.708 vs 0.668; P = 0.097). Superior discriminative ability was observed in the nomogram when compared with the FIGO staging system only in the primary cohort (C-index, 0.708 vs 0.578; P < 0.001). Decision curve analysis demonstrated that our nomogram was clinically useful.Conclusion We developed and validated a nomogram incorporating CA125 levels after three chemotherapy cycles for PFS prediction in ovarian cancer. This nomogram showed well-predictive performance and easy clinical application.
Response to treatment with Intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligo articular Juvenile Idiopathic arthritis
Authors: Masoud Rana , Jeelani Wajiha , Agbor Barbine Tchamba Agbor , Hennon Teresa , Wrotniak Brian H , Abdul-Aziz Rabheh
Published: September 2020

Background: Oligo-articular juvenile idiopathic arthritis (Oligo JIA) is the most common subtype of juvenile idiopathic arthritis. Intra-articular corticosteroid (IAC) injection is a mainstay treatment of oligo JIA providing pain relief, improving mobility and preventing further joint destruction in the majority of patients. In 2015, production of triamcinolone hexacetonide (TH) an intra-articular corticosteroid was discontinued in the United States leading to use of triamcinolone acetonide (TA) as an alternative. In this study, we compared response to treatment in children with oligo JIA who underwent therapy with intra-articular TA and TH injection. Methods: Our study is a retrospective chart review of children with oligo JIA who were treated with IAC injections with TH between January 2012 and June 2015 and TA between J uly 2015 and December 2018. The two groups were followed at John R. Oishei Children’s Hospital of Buffalo and were evaluated for response to treatment, side effects and predictors of response including duration of disease before treatment, erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Response to treatment was defined as at least 6 months follow up without evidence of active arthritis in injected joints. Patients were considered to be non-responders if they continued to show active arthritis during their first follow up after joint injection. The primary objective was to evaluate whether there was a significant difference in rate of response between TH and TA. Results: Forty-nine patients, 38 female and 11 male with oligo JIA were included in the study. The average age was 6.7 years. A total of 111 joints were injected includin g 78 knees, 13 ankles, 9 wrists, 4 hips, 4 elbows, 2 TMJ and one subtalar joint. In the TA group, 49 % (29/59) did not show response to injection compared to 27 % (14/52) in the TH group. After 6 months, response rates were better for individuals injected with TH compared to TA (73 % vs. 51%). In general, response to intra-articular TH was superior to TA with P = .016 using chi-square test of independence. This difference in outcome was not influenced by other variables such as duration of illness before treatment (P value 0.784) or elevated ESR and CRP. No difference in side effects between the two groups were noted. Conclusion: Our results in conjunction with prior published data suggests that TH intra-articular joint injection in oligo JIA is superior to TA, although future controlled trials are necessary for confirmation. An effective, long lasting treatment can have a great impact on the outcome of these children.
Novel concepts in cervical cancer screening. A comparison of VIA, HPV DNA test and p16INK4a/Ki-67 dual stain cytology in Western Kenya.
Authors: Orang’o Elkanah Omenge , Were Edwin , Rode Oliver , Muthoka Kapten , Byczkowski Michael , Sartor Heike , Broeck Davy Vanden , Schmidt Dietmar , Reuschenbach Miriam , Doeberitz Magnus von Knebel , Bussmann Hermann
Published: September 2020

Background: Screening of unvaccinated women remains essential to mitigate the high morbidity/mortality of cervical cancer. Here, we compared visual inspection with acetic acid (VIA), recommended by WHO as the most cost-effective screening approach in LMICs, with HPV-based screening, and usage of p16INK4a/Ki-67 dual stain cytology.Methods: We prospectively enrolled women participating in a VIA-based cervical cancer screening program in two peri-urban health centers of Kenya. Consenting women had a VIA examination preceded by collection of a liquid-based cytology sample from the cervix stored in PreservCyt medium (Hologic®). Analysis of all samples included a hrHPV DNA test and evaluation of a p16INK4a /Ki-67 (CINtecPLUS®) dual stained slide that was prepared using the ThinPrep® 2000 Processor and evaluated by a pathologist trained in the methodology.Results: In 701 of a total of 800 women aged 18-64 years, all three investigations were performed and data could be analyzed. The HPV, VIA and dual stain cytology positivity were 33%, 7%, and 2% respectively. The HPV positivity rate of VIA positive cases was 32%. The five most common HPV types were HPV16, 52, 68, 58 and 35. The OR among HIV infected women of an HPV infection, VIA positivity and positive dual stain cytology were 2.6 (95%CI 1.5-4.3), 1.9 (95%CI 0.89-4.4) and 3.4 (95%CI 1.07-10.9) respectively. The sensitivity of VIA to detect a p16INK4a/Ki-67 positive transforming infection was 13% (95%CI 2-38). Conclusions: Primary HPV testing appears feasible and should be considered as a primary screening test also in LMICs. The poor sensitivity of VIA renders it unsuitable as a triage test for HPV positive women. The utility of p16INK4a/Ki-67 dual stain cytology as a triage test for HPV positive women in LMICs should be further studied.
Planning of births and childhood undernutrition in Nepal: evidence from a 2016 national survey
Authors: Tiwari Ishwar , Acharya Kiran , Paudel Yuba Raj , Sapkota Bhim Prasad , Kafle Ramesh Babu
Published: September 2020

Background: Childhood undernutrition is a significant public health issue in low-and middle-income countries, including Nepal. However, there is limited evidence showing the association between the planning of birth (PoB) and childhood undernutrition (stunting and underweight). We aimed to investigate the relationship between PoB and childhood undernutrition in the current study.Methods: We used the Nepal Demographic and Health Survey 2016 data, which is a nationally representative cross-sectional household survey. We used two common anthropometric indicators of childhood undernutrition as the outcome of this study. PoB is the main predictor of interest. Binary logistic regression with sampling weights was used to estimate adjusted odds ratios (OR) and 95% confidence intervals to examine the association between the PoB and childhood undernutrition.Results: The overall prevalence of stunting was 35.8%, and underweight was 27.1% in under-five children in Nepal. We found a higher rate of stunting (52.7%) and underweight (41.1%) in children with birth order >3 and <2 years of interval between birth and subsequent birth (IBBSB). The association between the birth order of children and the prevalence of undernutrition had strong statistical significance (p<0.001). Mother’s age at marriage (p=0.001), underweight mother (p<0.001), mother’s education (p<0.001), father’s education (p<0.001), wealth quintile (p<0.001), no exposure to mass media (p<0.001), children’s age (p<0.001), and place of residence(p=0.001) were significantly associated with childhood undernutrition. The result of the multiple logistic regression showed that children with birth order one and 12-24 months of interval between marriage and first birth (IBMFB) had significantly decreased odds of stunting as compared to those children with birth order one and <12 months of IBMFB (OR 0.6, 95% CI 0.4-0.9). Conclusion: The findings of the study demonstrate that PoB has a protective effect on childhood undernutrition. Delaying of childbirth until 12-24 months after marriage was found to be associated with reduced odds of childhood stunting. To mitigate childhood undernutrition, Nepal's government needs to promote delayed childbearing after marriage while focusing on uplifting the household economics status and wide coverage of and utilization of mass media.
The Prevalence and Causes of Visual Impairment among Children in Kenya – The Kenya Eye Study
Authors: Muma Shadrack , Obonyo Stephen
Published: September 2020

Background: Visual impairment is the partial or complete loss of vision and it is attributed to uncorrected refractive error. In Kenya, little attention has been directed towards children vision and causes of visual impairment. Therefore, this study was designed to investigate the prevalence and causes of visual impairment in the children population of Kenya.Methods: This cross-sectional population-based study included 3400 (1800, 52.9% female) randomly selected children with a mean age of 12 ± 2 years (range 5–16 years). Visual acuity was taken using Snellens chart at 6 meters. Anterior and posterior segment was assessed using slit lamp and indirect ophthalmoscope. The World Health Organization definition formed the baseline for calculating the mean prevalence of visual impairment.Results: Visual acuity measurements were available for 3240 (95.3%) participants. The mean prevalence of visual impairment, based on pin-hole value, using World Health Organization definition, was 1.7 ± 0.3%. The prevalence of visual impairment, based on presenting visual acuity value, was 2.4 ± 0.7%, using the World Health Organization definition. Multivariate analysis demonstrated that the presence of visual impairment on pin-hole, according to World Health Organization definition increased significantly with increasing age (odds ratio 1.230, P=.021) and increased uncorrected refractive error (odds ratio 0.834, P = .032). Cases of uncorrected refractive error remained the main cause for presenting visual impairment. Causes of visual impairment due to presenting visual acuity were nystagmus (14%), amblyopia (24%) and uncorrected refractive error (62%).Conclusion: The prevalence of visual impairment in Kenya is associated with age. Uncorrected refractive error remains the major causes of visual impairment.
Gut microbiota and fecal metabolites in captive and wild North China leopard (Panthera pardus japonensis) by comparsion using 16s rRNA gene sequencing and LC/MS-based metabolomics
Authors: Hua Yan , cao Heqin , Wang Jiao , He Fengping , Jiang Guangshun
Published: September 2020

Background: Gut microbes significantly contribute to nutrient digestion and absorption, intestinal health and immunity, and are essential for the survival and environmental adaptation of wild animals. However, there are few studies on the gut microbiota of captive and wild North China leopard (Panthera pardus japonensis). Results: A total of 10 mainly bacterial phyla were identified in the fecal microbiota of North China leopard, Lachnoclostridium (p = 0.003), Peptoclostridium (p = 0.005), Bacteroides (p =0.008), Fusobacterium (p = 0.017) and Collinsella (p = 0.019) were significantly higher than those of wild North China leopard. Distinct differences in the fecal metabolic phenotypes of captive and wild North China leopard were found, such as content of l-methionine, n-acetyl-l-tyrosine, pentadecanoic acid and oleic acid. Differentially abundant gut microbes were associated with fecal metabolites, especially the bacteria in Firmicutes and Bacteroidetes, involved in the metabolism of N-acetyl-L-alanine and D-quinovose.Conclusion: This study reports for the first time the differences in gut microbiota abundance between captive and wild North China leopard, as well as significant differences in fecal metabolic phenotypes between two groups.
Effects of the anesthesiologist's experience on postoperative hoarseness after double-lumen endotracheal tube intubation: A single-center propensity score-matched analysis
Authors: Kamimura Yuji , Nakanishi Toshiyuki , Sato(Boku) Aiji , Osaga Satoshi , Kako Eisuke , Sobue Kazuya
Published: September 2020

Background: Postoperative hoarseness after general anesthesia is associated with patient discomfort and dissatisfaction. A recent large retrospective study showed that single-lumen endotracheal tube intubation by a trainee did not alter the incidence of postoperative pharyngeal symptoms compared with intubation by a senior anesthesiologist. However, there is limited information about the relationship between the anesthesiologist’s experience and hoarseness after double-lumen endotracheal tube intubation. We tested the hypothesis that double-lumen endotracheal tube intubation performed by a trainee increases the incidence of postoperative hoarseness compared to intubation by a senior anesthesiologist.Methods: This retrospective observational study included patients who underwent lung resection between April 2015 and March 2018 at a university hospital. Double-lumen endotracheal tube intubation was carried out with a Macintosh laryngoscope. We divided the patients into two groups - one group comprised of patients who were intubated by a trainee anesthesiologist with < 2 years of experience, and the other group comprised of those who underwent intubation by a senior anesthesiologist with ≥ 2 years of experience. The primary outcome was the incidence of postoperative hoarseness 24 h after surgery and we collected data on postoperative hoarseness using a checklist of postanesthetic adverse events. One-to-one propensity score matching was conducted and P values <0.05 were considered statistically significant.Results: There was a total of 256 eligible patients, of which 153 underwent intubation by trainee anesthesiologists, and the remaining 103 patients were intubated by a senior anesthesiologist. The one-to-one propensity score matching resulted in 96 pairs of patients for the groups. The incidence of postoperative hoarseness 24 h after surgery was significantly higher in patients who were intubated by a trainee anesthesiologist than in patients who were intubated by a senior anesthesiologist (9.4% vs. 2.1%, respectively; P = 0.03).Conclusions: Double-lumen endotracheal tube intubation by trainee anesthesiologists with < 2 years of experience increased the incidence of postoperative hoarseness 24 h after surgery compared to intubation by senior anesthesiologists with ≥ 2 years of experience.
Contributing factors to severe complications after liver resection: an aggregate root cause analysis in 105 consecutive patients.
Authors: Houssaini Kholoud , Lahnaoui Oumayma , Souadka Amine , Majbar Mohamed-Anass , Ghannam Abdelilah , Ahmadi Brahim El , Belkhadir Zakaria , Amrani Leila , Mohsine Raouf , Benkabbou Amine
Published: September 2020

Background: The aggregate root cause analysis (AggRCA) was designed to improve the understanding of system vulnerabilities contributing to patient harm, including surgical complications. It remains poorly used due to methodological complexity and resource limitations. This study aimed to identify the main patterns contributing to severe complications after liver resection using an AggRCA.Methods: This was a retrospective qualitative study aimed to identify the main patterns contributing to severe complications, defined as strictly higher than grade IIIa according to the Clavien-Dindo classification within the first 90 days after liver resection. All consecutive severe complications that occurred between January 1st, 2018 and December 31st, 2019 were identified from an electronic database and included in an AggRCA. This included a structured morbidity and mortality review (MMR) reporting tool based on 50 contributory factors adapted from 6 ALARM categories: “Patient”, “Tasks”, “Individual staff”, “Team”, “Work environment”, and “Management and Institutional context”. Data resulting from individual-participant root cause analysis (RCA) of single-cases were validated collectively then aggregated. The main patterns were suggested from the contributory factors reported in more than half of the cases.Results: In 105 consecutive liver resection cases, 15 patients (14.3%) developed severe postoperative complications, including 5 (4.8%) who died. AggRCA resulted in the identification of 36 contributory factors. Eight contributory factors were reported in more than half of the cases and were compiled in three entangled patterns: (1) Disrupted perioperative process, (2) Unplanned intraoperative change, (3) Ineffective communication.Conclusion: A pragmatic aggregated RCA process improved our understanding of system vulnerabilities based on the analysis of a limited number of events and a reasonable resource intensity. The identification of patterns contributing to severe complications lay the rationale of future contextualized safety interventions beyond the scope of liver resections.
Coal petrology analysis and implications in depositional environments from Upper Cretaceous to Miocene: a study case in the Eastern Cordillera of Colombia
Authors: Guatame Clara , Rincón Marco
Published: September 2020

The Piedemonte Llanero basin is located on the eastern side of the Eastern Cordillera of the Colombian Andes. It has been the subject of numerous geological studies carried out for the oil sector, mainly. This study presents the coal-petrographical features of 15 coal seams of four geological formations from Late Cretaceous to Middle Miocene (Chipaque Formation, Palmichal Group, Arcillas del Limbo Formation, and San Fernando Formation). Analysis of 33 samples indicates enrichment in vitrinite, while liptinite and inertinite concentrations vary according to the stratigraphic position. Reflectance indicates that the coal range gradually decreases from highly volatile bituminous C (Chipaque Formation) to subbituminous C (San Fernando Formation). The microlithotypes with the highest concentrations are clarite and vitrinertoliptite.Maceral composition and coal facies indicate changes in the depositional conditions of the sequence. The precursor peat from Late Cretaceous to Late Paleocene accumulated under limnic conditions followed by telmatic in Late Eocene- Early Miocene. The coal facies indices show wet conditions in forest swamps with variations in the flooding surface, influxes of brackish water and good tissue preservation. The tectonic conditions along the Piedemonte Llanero basin is evident, from post-rift to foreland basin, evidenced by oxic and anoxic periods reflected in the maceral composition and its morphology. The coal environment corresponds to an estuarine system started in the Chipaque Formation evolving to the lacustrine conditions in the San Fernando Formation.
Potential Association Between Bacterial Infections and Ischemic Stroke Based on Fifty Case-Control Studies: A Systematic Review and Meta-Analysis
Authors: Keikha Masoud , Karbalaei Mohsen
Published: September 2020

Background: Stroke is considered as one of the most concerns in health services facilities worldwide, and occurs in two types, ischemic stroke and hemorrhagic stroke. However, almost the three quarters of stroke cases are ischemic stroke which occur in effect of several risk factors such as hypertension, obesity, atherosclerosis, diabetes mellitus, arteritis, and inflammatory response. In recent years, infectious diseases are considered as one of the most important risk factors of ischemic stroke. In this regard, some bacteria causing the chronic infections in particular Chlamydia pneumonia, Helicobacter pylori, Mycoplasma pneumonia, and Mycobacterium tuberculosis get more attended. Methods: In the present meta-analysis, we studied 50 case-control studies and evaluated potential relevance of these infections with creation and development of ischemic stroke. Results: We surveyed the information of 33,978 participants in several nested case-control studies and demonstrated that bacterial infections can increase the risk of ischemic stroke.Conclusions: In this meta-analysis we demonstrated a meaningful relationship between infection by three bacteria C. pneumoniae, H. pylori, and M. tuberculosis with occurrence of ischemic stroke.
Pre-HAART CD4+ T-Lymphocytes as Biomarkers of Post-HAART Immune Recovery in HIV-Infected Children with or without TB Co-Infection
Authors: Gopalakrishnan Vivek , Bose Eliezer , Nair Usha , Cheng Yuwei , Ghebremichael Musie
Published: September 2020

Background Infection with the Human Immunodeficiency Virus (HIV) dramatically increases the risk of developing active tuberculosis (TB). Several studies have indicated that co-infection with TB increases the risk of HIV progression and death. Sub-Saharan Africa bears the brunt of these dual epidemics, with about 2.4 million HIV-infected people living with TB. The main objective of our study was to assess whether the pre-HAART CD4+ T-lymphocyte counts and percentages could serve as biomarkers for post-HAART treatment immune-recovery in HIV-positive children with and without TB co-infection. Methods The data analyzed in this retrospective study were collected from a cohort of 305 HIV-infected children being treated with HAART. A Lehmann family of ROC curves were used to assess the diagnostic performance of pre- HAART treatment CD4+ T-lymphocyte count and percentage as biomarkers for post-HAART immune recovery. The Kaplan–Meier estimator was used to compare differences in post-HAART recovery times between patients with and without TB co-infection.Results We found that the diagnostic performance of both pre-HARRT treatment CD4+ T-lymphocyte count and percentage was comparable and achieved accuracies as high as 74%. Furthermore, the predictive capability of pre-HAART CD4+ T-lymphocyte count and percentage were slightly better in TB-negative patients. Our analyses also indicate that TB-negative patients have a shorter recovery time compared to the TB-positive patients. Conclusions Pre-HAART CD4+ T-lymphocyte count and percentage are stronger predictors of immune recovery in TB-negative pediatric patients, suggesting that TB co-infection complicates the treatment of HIV in this cohort. These findings suggest that the detection and treatment of TB is essential for the effectiveness of HAART in HIV-infected pediatric patients.
Molecular characterization and serodiagnostic potential of two serpin proteins in Psoroptes cuniculi
Authors: Gu Xiaobin , Chen Yuhang , Zhang Chongyang , Xie Yue , Shen Nengxing , Wang Ce , Zhou Xuan , Yang Guangyou , He Ran , Peng Xuerong , Yang Deying , He Zhi , Zhong Zhijun
Published: September 2020

Background: Psoroptes cuniculi is a global common ectoparasite of wild and domestic rabbits and causes an economically devastating loss and serious welfare issues of commercial rabbit husbandry. Serine proteinase inhibitor (Serpin) is present in almost all organisms that are involved in host-pathogen interactions, inflammatory responses, and reproductive development, etc. However, the research on P. cuniculi serpins is still limited.Methods: In this study, two serpin genes of P. cuniculi (Pso c 27 and PsoSP2 cDNAs) were cloned, and the molecular characterization was analyzed. The transcriptional profiles and tissue localization of these two serpins in P. cuniculi were investigated by quantitative real-time PCR and immunohistochemistry, respectively. The potential function of recombinant Pso c 27 and PsoSP2 (rPso c 27and rPsoSP2) in the serodiagnosis of P. cuniculi infestation in rabbits were evaluated by indirect enzyme-linked immunosorbent assay (iELISA). Results: Both of the 523 residue Pso c 27 and the 240 residue PsoSP2 proteins contained typical serpin domains and signatures. Both Pso c 27and PsoSP2 cDNAs expressed throughout the life cycle, more specifically, significantly higher expression in female mites than the larva, nymph, and male mites (p < 0.001). The native Pso c 27 and PsoSP2 localized in ovary and mouthpart of adult female mites, respectively. Compared to rPsoSP2, the rPso c 27 displayed better diagnostic efficiency with higher values of sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) (rPso c 27 - rPsoSP2: 96.0% - 90.0%; 90.91% - 78.18%; 0.988 - 0.964, respectively). Moreover, the rPso c 27 showed seropositive in 80% rabbits as early as the 2nd week post-infestation (p.i.), prior to visible clinical signs and microscopy-positive of skin scrapings. Conclusions: These results suggested that these two serpins may play essential roles in reproductive development, serum-feeding, and pathogenicity of P. cuniculi. Compared to PsoSP2, Pso c 27 appeared as a potential antigen for serodiagnosis of P. cuniculi infestation in rabbits, especially at the early stage of infestation.
A collagen membrane influences bone turnover marker in vivo after bone augmentation with xenogenic bone
Authors: Staedt Henning , Dau Michael , Schiegnitz Eik , Thiem Daniel G.E. , Tagadiuc Olga , Palarie Victor , Ottl Peter , Al-Nawas Bilal , Kammerer Peer W
Published: September 2020

Background: The aim was to compare early biochemical and histological osseous healing of chronic mandibular defects regenerated with bovine bone substitute with and without collagen membrane in vivo.Methods: Eight weeks after formation of a lateral full-thickness two-wall defect in the mandible of 40 rabbits, bovine bone substitute with (“+”;n=20) and without (“-“;n=20) collagen membrane was applied. Blood and bone was collected 24, 72 hours, 7, 14 and 21 days after surgery. Total acid phosphatase, bone acid phosphatase, total alkaline phosphatase and bone alkaline phosphatase activities were compared between groups. Formation of new bone was quantified histologically for all time points.Results: Twenty-four hours after surgery, bone alkaline phosphatase was significantly elevated in “+” group when compared to “-“ (p=0.012). After 72 hours, all bone turnover markers except for total acid phosphatase (p=0.078) where significantly elevated in “+” (all p<0.05). 14 days after surgery, the significant highest values for all bone turnover markers were detected in “-“ (all p<0.05). A significant difference in favor of group “-“ could also be detected after 3 weeks in terms of both acid phosphatases (p<0.05). In histology, no significant differences could be detected.Conclusion: Bone regeneration with bovine bone substitute material and collagen membrane shows a significantly earlier bone remodeling activity but does not seem to influence formation of new bone in histological samples.
Binding of human serum proteins to P. falciparum-infected erythrocytes and its association with malaria clinical presentation 
Authors: Lopez-Perez Mary , Puije William van der , Castberg Filip C. , Ofori Michael F. , Hviid Lars
Published: September 2020

BackgroundThe pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite‑infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α2‑macroglobulin (α2M), to increase the avidity of PfEMP1-mediated binding to erythrocyte receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here.MethodsChildren 1-12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α2M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α2M was also evaluated. Experimental results were analysed according to the clinical presentation of the patients.ResultsClinical data from 108 children classified as UM (n=54) and SM cases (n=54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from UM (n=14) and SM (n=20) children were analysed. Most of the field isolates bound non‑immune IgM (33/34), whereas the α2M-binding was less common (23/34). Binding of both non-immune IgM and α2M was higher but not significant in IEs from children with SM than from children with UM. In combination, IgM and α2M supported rosette formation at levels similar to that observed in the presence of 10% human serum.ConclusionsThe results support the hypothesis that binding of non-immune IgM and/or α2M to IEs facilitates rosette formation and perhaps contributes to P. falciparum malaria severity.
Numerical study on the influence of initial ambient temperature on the aerodynamic heating in the tube train system
Authors: Bao Shijie , Hu Xiao , Wang Jukun , Ma Tianhao , Rao Yingyu , Deng Zigang
Published: September 2020

The evacuated tube transportation has great potential in the future because of its advantages of energy saving and environmental protection. The train runs in the closed tube at ultra-high speed. Because the heat quantity generated by aerodynamic heating is not easy to spread to external environment and will accumulate in the tube, the phenomenon that the ambient temperature in the tube will gradually rise will be induced. In this paper, a three-dimensional geometric model and the Shear Stress Transport (SST) κ-ω turbulence model are used to study the influence of initial ambient temperature on the structure of the flow field in the tube. Simulation results show that when the train runs at transonic speed, the supersonic flow region with low temperature and low-pressure is produced in the wake. The structure of the flow field of the wake will change with the initial ambient temperature. And the higher the initial ambient temperature, the shorter the low temperature region in the wake. The larger temperature difference caused by the low temperature region may increase the temperature stress of the tube and affect the equipment inside the tube. Consequently, the temperature inside the tube can be maintained at a reasonable value to reduce the influence of the low temperature region in the wake on the system.
Deregulation and pricing of medical services: A policy experiment based in China
Authors: Zang Wenbin , Zhou Mei , Zhao Shaoyang
Published: September 2020

Background: Price regulation is a common constraint in Chinese hospitals. Based on a policy experiment conducted in China on the price deregulation of private nonprofit hospitals, this study empirically examines the impact of medical service price regulation on the pricing of medical services by hospitals. Methods: Using the claim data of insured inpatients residing in a major Chinese city for the period 2010–2015, this study constructs a DID (difference-in-differences) model to compare the impact of price deregulation on medical expenditure and expenditure structure between public and private nonprofit hospitals. Results: The empirical results based on micro data reveal that, price deregulated significantly increased the total expenditure per inpatient visit by 10.5%. In the itemized expenditure, the diagnostic test and drug expenditure per inpatient visit of private nonprofit hospitals decreased significantly, whereas the physician service expenditure per inpatient visit increased significantly. For expenditure structure, the proportions of drug expenditure and diagnostic test expenditure per inpatient visit significantly decreased by 5.7% and 3.1%, respectively. Conclusions: Under price regulation, medical service prices generally become lower than their costs. Therefore, after price deregulation, private nonprofit hospitals increase medical service prices above their cost and achieve the service premium by providing high-quality medical services and a comfortable medical environment. Further, although price deregulation causes patient expenditure to increase to a certain level, it optimizes the expenditure structure, as well.
Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9
Authors: Zhang Ting , Lu Rui , Chen Yibing , Yuan Yuguo , Song Shaozheng , Yan Kunning , Zha Yiwen , Zhuang Wenwen , Cheng Yong , Liang Jingyan
Published: September 2020

Background: Congenital hyper-homocysteinemia (HHcy) is caused by a defective cystathionine β-synthase (CBS) gene, and is frequently associated with dyslipdemia. The aim of this study was to further elucidate the effect of mutated CBS gene on circulating lipids using a rabbit model harboring a homozygous G307S point mutation in CBS.Methods: CRISPR/Cas9 system was used to edit the CBS gene in rabbit embryos. The founder rabbits were sequenced, and their plasma homocysteine (Hcy) and lipid profile were analyzed.Results: Six CBS-knockout (CBS-KO) founder lines with biallelic modifications were obtained. Mutation in CBS caused significant growth retardation and high mortality rates within 6 weeks after birth. In addition, the 6-week old CBS-KO rabbits showed higher plasma levels of Hcy, triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the age-matched wild-type (WT) controls. Histological analysis of the mutants showed accumulation of micro-vesicular cytoplasmic lipid droplets in the hepatocytes. However, gastric infusion of vitamin B and betaine complex significantly decreased the plasma levels of TG, TC and LDL-C in the CBS-KO rabbits, and alleviated hepatic steatosis compared to the untreated animals.Conclusion: A CBSG307S rabbit model was generated that exhibited severe dyslipidemia when fed on a normal diet, indicating that G307S mutation in the CBS gene is a causative factor for dyslipidemia.
Clinical Features of Trousseau's Syndrome with Multiple Acute Ischemic Strokes
Authors: Ling Yitong , Li Yinye , Zhang Xiaoyu , Dong Lihua , Yao Dongxiao , Wang Jin-Tao
Published: September 2020

Background:Trousseau’s syndrome can cause venous or arterial thrombosis, multiple acute ischemic strokes (MAIS) caused by Trousseau’s syndrome is rare. The aim of this study was to analyze the clinical features of Trousseau's syndrome with MAIS, and to improve the awareness and the knowledge of this disease.Methods:Clinical data from fifteen patients who were diagnosed as Trousseau's Syndrome with MAIS in Rizhao people's Hospital from January 2017 to April 2020 were collected and analyzed. The clinical data included the following: Patients’ basic information, laboratory results, imaging features, treatment regimens, and short-term prognoses were collected.Results:The mean age was 65.5 years, with thirteen males and two females. Most patients (11/15) had a history of smoking and (or) drinking. The average score of NIHSS was 2.13. 6 of the 15 patients first presented with ischemic stroke, and then found the primary tumor. Most common types of primary tumor was lung cancer (11/15), other types of primary tumor were gastric adenocarcinoma, renal cell carcinoma, esophageal adenosquamous carcinoma, and cholangiocarcinoma (one in each). All the 15 patients showed different levels of increase of D-dimer. The increase in CRP appears in 10 of the 15 patients. Various tumor markers were increased in the 15 patients, Especially for CYFRA-211, all the patients of which were higher than normal. All of the 15 patients had multiple vascular territories lesions in DWI, and most lesions were near the cortex areas. Only 4 of the 15 patients (26.7%) occurred with Peripheral venous thrombosis. 13 patients were given low molecular heparin for anticoagulant therapy, of which 9 patients were improved in short-term while 4 patients were not.Conclusion:Trousseau's syndrome with MAIS was associated with old-age male, smoking and (or) drinking history, low NIHSS score, increased D-dimer, CRP and tumor markers, lesions near the cortex areas with multiple vascular territories in DWI. Patients with these features should be alert of malignant tumor. Most common types of primary tumor were lung cancer. Treatment with Low molecular heparin may be effective in short-term.
Donor Derived Cell Free DNA Kinetics Post Kidney Transplant Biopsy
Authors: Kyeso Yousuf , Bhalla Anshul , Smith Alyssa P , Jia Yaqi , Alakhdhair Safa , Ogir Stephanie C , Abuzeineh Mohammad , Brennan Daniel C , Alasfar Sami
Published: September 2020

Background:Donor-derived cell-free DNA (dd-cfDNA) has generated interest as a biomarker for kidney transplant (KT) rejection. It is possible that the KT biopsy procedure can cause the release of dd-cfDNA, therefore affecting the reliability of this assay in the post biopsy period. In this study we evaluated the effect of KT biopsy on the kinetics of dd-cfDNA.Methods:We conducted a single arm prospective study. Samples were collected from 16 adult KT recipients undergoing KT biopsy. All participants had samples drawn within eight hours prior to the biopsy (pre-biopsy), within 20 minutes (hour 0), 2 hours (hour 2), and 24-48 hours (hours 24-48) after the biopsy. We evaluated the change in dd-cfDNA from the pre-biopsy time point to the following 3 time points after the biopsy.Results:At hour 0 and hour 2, there was a significantly larger log dd-cfDNA mean score compared to the pre-biopsy score [Least square mean (LSM) estimate 0.4 (0.17, 0.63) and 0.39 (0.09, 0.68) respectively]. By 24-28 hours post biopsy there was no significant difference in log dd-cfDNA mean score compared to the pre-biopsy score [LSM estimate -0.21 (-0.6, 0.19)]. Conclusion:KT biopsy leads to an increase in dd-cfDNA after the procedure, however, this rise is transient and resolves by 24-48 hour after the biopsy. Providers can obtain dd-cfDNA level as soon as 48 hours post biopsy with high confidence that the levels have not been affected by the biopsy. In addition, our findings suggest possible non-traditional reasons for increase in dd-cfDNA such as mechanical reasons.
Deciphering Disparities in Childhood Stunting in an Underdeveloped State of India: An Investigation Applying the Unconditional Quantile Regression Method
Authors: Ghosh Saswata , Sharma Santosh Kumar , Bhattacharya Debarshi
Published: September 2020

BackgroundUnacceptably high rate of childhood stunting for decades remained a puzzle in the eastern Indian state of Bihar. Despite various programmatic interventions, nearly half of the under-five children (numerically about 10 million) are still stunted in this resource-constrained state. Data and MethodsUsing four successive rounds of National Family Health Survey (NFHS) data spread over more than two decades and by employing quantile regressions and counterfactual decomposition (QR-CD), the present study aims to assess effects of various endowments as well as returns to those endowments in disparities in childhood stunting over the period. Results The results show that although the child’s height-for-age Z-scores (HAZ) disparity largely accounted for differing levels of endowments during the earlier decades, in the later periods, inadequate access to the benefits from various development programmes was also found responsible for HAZ disparities. Moreover, effects of endowments and their returns varied across quantiles. We argue that apart from equalizing endowments, ensuring adequate access to different nutrition-centric programmes is essential to lessen the burden of childhood stunting. ConclusionThe state must focus on intersectoral convergence of different schemes in the form of state nutrition mission, and, strengthen nutrition-centric policy processes and their political underpinnings to harness better dividend.
A Case Report of Classical Gastrointestinal Stromal Tumor with an Undifferentiated Pleomorphic Sarcoma Component
Authors: Hu YiFan , JIAN SHUNHAI , wen bin , he linli , huang yifan
Published: September 2020

Background:Gastrointestinal stromal tumor (GIST) is the most common primary mesenchymal neoplasm of the gastrointestinal tract.a small number of GIST patients showed morphologic and immunohistochemical phenotypes change after taking the selective tyrosine kinase inhibitor imatinib.Case presentation :A 64-year-old Asian man was referred to a hospital for dizziness and anemia. Then the patient received imatinib for 11 months after the discovery of a gastric stromal tumor, and had the tumor surgically removed. We found that the classical GIST region was juxtaposed to a undifferentiated component of pleomorphic sarcoma. The genetic test results of the patient showed that the 11 exon of C-Kit gene was homozygous deletion, and the 567 codon of the 12 exon of PDGFRα was homozygous mutation. We infer that the patient showed rare dedifferentiation change after taking the tyrosine kinase inhibitors (TKIs) imatinib（IM）.Conclusions:Together with reported cases, awareness of this rare clinical entity and its potential occurrence following Tyrosine kinase inhibitor (TKI)treatment could prevent a diagnostic pitfall. The case report reminds us of the diagnosis in GIST that the possibility of dedifferentiation in GISTs should always be considered when an undifferentiated sarcoma component is identified in the gastrointestinal tract.