bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracorporeal membrane oxygenation in trauma patients: a systematic review
Authors: Wang Changtian , Zhang Lei , Qin Tao , Xi Zhilong , Sun Lei , Wu Haiwei , Li Demin
Published: September 2020

Background

Extracorporeal membrane oxygenation (ECMO) has evolved considerably over the past two decades and has been gradually utilized in severe trauma. However, the indications for the use of ECMO in trauma remain uncertain and the clinical outcomes are different. We performed a systematic review to provide an overall estimate of the current performance of ECMO in the treatment of trauma patients.

Materials and methods

We searched PubMed and MEDLINE databases up to the end of December 2019 for studies on ECMO in trauma. The PRISMA statement was followed. Data on demographics of the patient, mechanism of injury, injury severity scores (ISS), details of ECMO strategies, and clinical outcome were extracted.

Results

A total of 58 articles (19 retrospective reports and 39 case reports) were deemed eligible and included. In total, 548 patients received ECMO treatment for severe trauma (adult 517; children 31; mean age of adults 34.9 ± 12.3 years). Blunt trauma (85.4%) was the primary injury mechanism, and 128 patients had traumatic brain injury (TBI). The mean ISS was 38.1 ± 15.0. A total of 71.3% of patients were initially treated with VV ECMO, and 24.5% were placed on VA ECMO. The median time on ECMO was 9.6 days, and the median time to ECMO was 5.7 days. A total of 60% of patients received initially heparin anticoagulation. Bleeding (22.9%) and thrombosis (19%) were the most common complications. Ischemia of the lower extremities occurred in 9 patients. The overall hospital mortality was 30.3%.

Conclusions

ECMO has been gradually utilized in a lifesaving capacity in severe trauma patients, and the feasibility and advantages of this technique are becoming widely accepted. The safety and effectiveness of ECMO in trauma require further study. Several problems with ECMO in trauma, including the role of VA-ECMO, the time to institute ECMO, and the anticoagulation strategy remain controversial and must be solved in future studies.
Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis
Authors: Tang Jia Zhu , Nie Ming Jun , Zhao Jian Zhong , Zhang Guang Cheng , Zhang Qing , Wang Bo
Published: September 2020

Background

This study aimed to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection compared with hyaluronic acid (HA) injection for patients undergoing knee osteoarthritis.

Methods

We systematically searched electronic databases including PubMed, Embase, Web of Science, and the Cochrane Library on January 23, 2020 to identify relevant studies issued in English languages. The outcomes evaluating the efficacy of knee osteoarthritis (KOA) treatment were Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (WOMAC pain, function, stiffness, and total scores) at 1, 3, 6, and 12 months; International Knee Documentation Committee (IKDC) scores, Lequesne Index score, Visual Analog Scale (VAS) scores, EQ-VAS scores, and KOOS scores. The pooled data were analyzed by Stata 12.0.

Results

A total of 20 RCTs were enrolled in the present meta-analysis. The pooled results demonstrated that platelet-rich plasma (PRP) injection reduced pain more effectively than hyaluronic acid (HA) injection at 6-month and 12-month follow-up evaluated by WOMAC pain scores and VAS scores. EQ-VAS in the patients treated with PRP injection was lower than that in patients with HA injection at 12 months. Moreover, the patients with PRP injection had a better function recovery than those with HA injection at 1-month, 3-month, 6-month, and 12-month follow-up, as evaluated by WOMAC function scores. WOMAC total scores showed significant difference at 6-month and 12-month follow-up. The IKDC scores indicated PRP injection was significantly more effective than HA injection at 3 months and 6 months. However, the Lequesne Index scores, KOOS scores, and adverse events did not show any significant difference between groups.

Conclusion

Intra-articular PRP injection appeared to be more efficacious than HA injection for the treatment of KOA in terms of short-term functional recovery. Moreover, PRP injection was superior to HA injection in terms of long-term pain relief and function improvement. In addition, PRP injection did not increase the risk of adverse events compared to HA injection.
Surgical treatment for secondary aortoesophageal fistula
Authors: Sugiyama Kayo , Iwahashi Toru , Koizumi Nobusato , Nishibe Toshiya , Fujiyoshi Toshiki , Ogino Hitoshi
Published: September 2020

Background

Aortoesophageal fistula (AEF) is a relatively rare condition that is often life-threatening. Secondary AEF is a complication of previous surgery, which can be more critical and challenging than primary AEF. The number of secondary AEF is increasing due to increase in the number of thoracic endovascular aortic repair (TEVAR). Although TEVAR has become a successful alternative surgical strategy for thoracic aortic aneurysms, secondary AEF after TEVAR might be critical than other secondary AEF because of severe adhesion between the esophagus and residual thoracic aortic wall.

Methods

This study analyzed six patients with secondary AEF who were treated at Tokyo Medical University Hospital between 2011 and 2016. These participants included four patients who had undergone TEVAR and two who had undergone total arch replacement.

Results

Although they were subsequently hospitalized for a long period, open surgical repair was completed in two patients who had undergone total arch replacement. TEVAR alone was performed in two patients who had undergone TEVAR and they were discharged without major complications shortly. Combined repair of TEVAR as a bridge to open surgery was planned for two patients who had undergone TEVAR. However, reconstruction of the aorta and esophagus could not be completed in these patients due to severe adhesions, and they died during hospitalization.

Conclusions

Definitive open repair was successfully performed in patients with secondary AEF after total arch replacement. However, in the patients with secondary AEF after TEVAR, severe adhesion between the aorta and esophagus led to difficulty in performing a successful definitive open repair. The strategy for secondary AEF should, therefore, be decided considering the etiology of secondary AEF. In secondary AEF after TEVAR, definitive open repair is difficult to complete because of catastrophic complication, and palliative treatment using TEVAR without reconstruction of aorta and esophagus can be an alternative.
The Alzheimer’s disease-associated protective Plcγ2-P522R variant promotes immune functions
Authors: Takalo Mari , Wittrahm Rebekka , Wefers Benedikt , Parhizkar Samira , Jokivarsi Kimmo , Kuulasmaa Teemu , Mäkinen Petra , Martiskainen Henna , Wurst Wolfgang , Xiang Xianyuan , Marttinen Mikael , Poutiainen Pekka , Haapasalo Annakaisa , Hiltunen Mikko , Haass Christian
Published: September 2020

Background

Microglia-specific genetic variants are enriched in several neurodegenerative diseases, including Alzheimer’s disease (AD), implicating a central role for alterations of the innate immune system in the disease etiology. A rare coding variant in the PLCG2 gene (rs72824905, p.P522R) expressed in myeloid lineage cells was recently identified and shown to reduce the risk for AD.

Methods

To assess the role of the protective variant in the context of immune cell functions, we generated a Plcγ2-P522R knock-in (KI) mouse model using CRISPR/Cas9 gene editing.

Results

Functional analyses of macrophages derived from homozygous KI mice and wild type (WT) littermates revealed that the P522R variant potentiates the primary function of Plcγ2 as a Pip2-metabolizing enzyme. This was associated with improved survival and increased acute inflammatory response of the KI macrophages. Enhanced phagocytosis was observed in mouse BV2 microglia-like cells overexpressing human PLCγ2-P522R, but not in PLCγ2-WT expressing cells. Immunohistochemical analyses did not reveal changes in the number or morphology of microglia in the cortex of Plcγ2-P522R KI mice. However, the brain mRNA signature together with microglia-related PET imaging suggested enhanced microglial functions in Plcγ2-P522R KI mice.

Conclusion

The AD-associated protective Plcγ2-P522R variant promotes protective functions associated with TREM2 signaling. Our findings provide further support for the idea that pharmacological modulation of microglia via TREM2-PLCγ2 pathway-dependent stimulation may be a novel therapeutic option for the treatment of AD.
Cross-sectional study for the clinical application of extracorporeal membrane oxygenation in Mainland China, 2018
Authors: Cheng Wei , Ma Xu-Dong , Su Long-Xiang , He Huai-Wu , Wang Lu , Tang Bo , Du Wei , Zhou Yuan-kai , Wang Hao , Cui Na , Long Yun , Liu Da-Wei , Guo Yan-Hong , Wang Ye , Shan Guang-Liang , Zhou Xiang , Zhang Shu-Yang , Zhao Yu-Pei
Published: September 2020

Background

To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018.

Methods

Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database.

Results

The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31–63), and 1346 were male. The average hospital stay was 17 days (IQR 7–30), and the average costs per case was $36,334 (IQR 22,547–56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality.

Conclusions

Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.
VeSpAR trial: a randomized controlled trial comparing vessel-sparing anastomotic repair and transecting anastomotic repair in isolated short bulbar urethral strictures
Authors: Verla Wesley , Waterloos Marjan , Waterschoot Mieke , Van Parys Benjamin , Spinoit Anne-Françoise , Lumen Nicolaas
Published: September 2020

Background

Vessel-sparing anastomotic repair (vsAR) has been developed as a less traumatic alternative to transecting anastomotic repair (tAR) to treat isolated short bulbar urethral strictures. This vessel-sparing technique could result in improved functional outcomes without jeopardizing the excellent surgical outcome after (transecting) anastomotic repair. The purpose of this study is to directly compare vsAR and tAR for both surgical and functional outcomes.

Methods

This trial is a prospective, interventional, multi-center, single-blinded, 1:1 randomized, controlled, non-inferiority, phase II trial. Sample size calculation resulted in a required sample size of 100 patients (50 patients per arm). Trial participants will be randomized by an independent third party using a computer-based random sequence generator with permuted blocks of variable size. The primary objective of this trial is to show that vsAR is non-inferior to tAR in terms of failure-free survival after 24 months of follow-up, considering a non-inferiority limit of 10%. Failure is defined as the inability to pass a 16-Fr flexible cystoscope through the reconstructed area without damaging the urethral mucosa. Secondary end-points mainly include differences in postoperative complications and changes in functional outcome parameters, which will be assessed with validated questionnaires. All participants are scheduled for follow-up at 3, 12, and 24 months postoperatively.

Discussion

This trial will provide level Ib evidence about the differences in both surgical and functional outcome between vsAR and tAR, which may importantly scape the future of bulbar urethral reconstruction. Depending on the trial results, this phase II trial may generate a larger phase III trial with more statistical power and a lower alpha value.

Trial registration

This trial is registered at clinicaltrials.gov (NCT03572348) and in the Belgian Clinical Trial Registry (B670201837335). The trial was registered prospectively. Registered on 28 June 2018.
Efficacy of Fludora® Fusion (a mixture of deltamethrin and clothianidin) for indoor residual spraying against pyrethroid-resistant malaria vectors: laboratory and experimental hut evaluation
Authors: Fongnikin Augustin , Houeto Nadia , Agbevo Abel , Odjo Abibath , Syme Thomas , N’Guessan Raphael , Ngufor Corine
Published: September 2020

Background

A new generation of IRS insecticides which can provide improved and prolonged control of pyrethroid-resistant malaria vector populations are being developed. Fludora® Fusion is a new IRS insecticide containing a mixture of deltamethrin and clothianidin, a neonicotinoid.

Methods

The efficacy of Fludora® Fusion IRS was evaluated over 11–12 months on concrete and mud substrates in laboratory bioassays and experimental huts against wild free-flying pyrethroid-resistant Anopheles gambiae (sensu lato) in Cové, Benin. A comparison was made with the two active ingredients of the mixture; clothianidin and deltamethrin, applied alone. CDC bottle bioassays were also performed to investigate resistance to clothianidin in the wild vector population.

Results

Fludora® Fusion induced > 80% laboratory cone bioassay mortality with both susceptible and pyrethroid-resistant An. gambiae (s.l.) for 7–9 months on concrete block substrates and 12 months on mud block substrates. The vector population at the experimental hut site was fully susceptible to clothianidin in CDC bottle bioassays. Overall mortality rates of wild free-flying pyrethroid-resistant An. gambiae (s.l.) entering the experimental huts during the 11-month trial were < 15% with deltamethrin and significantly higher with Fludora® Fusion (69–71%) and clothianidin alone (72–78%). Initial high experimental hut mortality rates with Fludora® Fusion (> 80%) only declined by 50% after 8 months. Monthly in situ wall cone bioassay mortality of susceptible mosquitoes was > 80% for 9–12 months with Fludora® Fusion and clothianidin alone. Fludora® Fusion induced significantly higher levels of early exiting of mosquitoes compared to clothianidin alone (55–60% vs 37–38%, P < 0.05).

Conclusions

Indoor residual spraying with Fludora® Fusion induced high and prolonged mortality of wild pyrethroid-resistant malaria vectors for 7–10 months mostly due to the clothianidin component and substantial early exiting of mosquitoes from treated huts due to the pyrethroid component. Fludora® Fusion is an important addition to the current portfolio of IRS insecticides with the potential to significantly reduce transmission of malaria by pyrethroid-resistant mosquito vectors.
Evidence for germline non-genetic inheritance of human phenotypes and diseases
Authors: Senaldi Liana , Smith-Raska Matthew
Published: September 2020

It is becoming increasingly apparent that certain phenotypes are inherited across generations independent of the information contained in the DNA sequence, by factors in germ cells that remain largely uncharacterized. As evidence for germline non-genetic inheritance of phenotypes and diseases continues to grow in model organisms, there are fewer reports of this phenomenon in humans, due to a variety of complications in evaluating this mechanism of inheritance in humans. This review summarizes the evidence for germline-based non-genetic inheritance in humans, as well as the significant challenges and important caveats that must be considered when evaluating this process in human populations. Most reports of this process evaluate the association of a lifetime exposure in ancestors with changes in DNA methylation or small RNA expression in germ cells, as well as the association between ancestral experiences and the inheritance of a phenotype in descendants, down to great-grandchildren in some cases. Collectively, these studies provide evidence that phenotypes can be inherited in a DNA-independent manner; the extent to which this process contributes to disease development, as well as the cellular and molecular regulation of this process, remain largely undefined.
Amyloid-β1–43 cerebrospinal fluid levels and the interpretation of APP, PSEN1 and PSEN2 mutations
Authors: Perrone Federica , Bjerke Maria , Hens Elisabeth , Sieben Anne , Timmers Maarten , De Roeck Arne , Vandenberghe Rik , Sleegers Kristel , Martin Jean-Jacques , De Deyn Peter P. , Engelborghs Sebastiaan , van der Zee Julie , Van Broeckhoven Christine , Cacace Rita ,   on behalf of the BELNEU Consortium, Goeman Johan , Crols Roeland , Dermaut Bart , Ivanoiu Adrian , Hanseeuw Bernard , Deryck Olivier , Bergmans Bruno , Versijpt Jan , Pharmaceutica Janssen , Saido Takaomi
Published: September 2020

Background

Alzheimer’s disease (AD) mutations in amyloid precursor protein (APP) and presenilins (PSENs) could potentially lead to the production of longer amyloidogenic Aβ peptides. Amongst these, Aβ1–43 is more prone to aggregation and has higher toxic properties than the long-known Aβ1–42. However, a direct effect on Aβ1–43 in biomaterials of individuals carrying genetic mutations in the known AD genes is yet to be determined.

Methods

N = 1431 AD patients (n = 280 early-onset (EO) and n = 1151 late-onset (LO) AD) and 809 control individuals were genetically screened for APP and PSENs. For the first time, Aβ1–43 levels were analysed in cerebrospinal fluid (CSF) of 38 individuals carrying pathogenic or unclear rare mutations or the common PSEN1 p.E318G variant and compared with Aβ1–42 and Aβ1–40 CSF levels.

The soluble sAPPα and sAPPβ species were also measured for the first time in mutation carriers.

Results

A known pathogenic mutation was identified in 5.7% of EOAD patients (4.6% PSEN1, 1.07% APP) and in 0.3% of LOAD patients. Furthermore, 12 known variants with unclear pathogenicity and 11 novel were identified. Pathogenic and unclear mutation carriers showed a significant reduction in CSF Aβ1–43 levels compared to controls (p = 0.037; < 0.001). CSF Aβ1–43 levels positively correlated with CSF Aβ1–42 in both pathogenic and unclear carriers and controls (all p < 0.001). The p.E318G carriers showed reduced Aβ1–43 levels (p < 0.001), though genetic association with AD was not detected. sAPPα and sAPPβ CSF levels were significantly reduced in the group of unclear (p = 0.006; 0.005) and p.E318G carriers (p = 0.004; 0.039), suggesting their possible involvement in AD. Finally, using Aβ1–43 and Aβ1–42 levels, we could re-classify as “likely pathogenic” 3 of the unclear mutations.

Conclusion

This is the first time that Aβ1–43 levels were analysed in CSF of AD patients with genetic mutations in the AD causal genes. The observed reduction of Aβ1–43 in APP and PSENs carriers highlights the pathogenic role of longer Aβ peptides in AD pathogenesis. Alterations in Aβ1–43 could prove useful in understanding the pathogenicity of unclear APP and PSENs variants, a critical step towards a more efficient genetic counselling.
A facile and scalable in production non-viral gene engineered mesenchymal stem cells for effective suppression of temozolomide-resistant (TMZR) glioblastoma growth
Authors: Tu Geraldine Xue En , Ho Yoon Khei , Ng Zhi Xu , Teo Ke Jia , Yeo Tseng Tsai , Too Heng-Phon
Published: September 2020

Background

Mesenchymal stem cells (MSCs) serve as an attractive vehicle for cell-directed enzyme prodrug therapy (CDEPT) due to their unique tumour-nesting ability. Such approach holds high therapeutic potential for treating solid tumours including glioblastoma multiforme (GBM), a devastating disease with limited effective treatment options. Currently, it is a common practice in research and clinical manufacturing to use viruses to deliver therapeutic genes into MSCs. However, this is limited by the inherent issues of safety, high cost and demanding manufacturing processes. The aim of this study is to identify a facile, scalable in production and highly efficient non-viral method to transiently engineer MSCs for prolonged and exceptionally high expression of a fused transgene: yeast cytosine deaminase::uracil phosphoribosyl-transferase::green fluorescent protein (CD::UPRT::GFP).

Methods

MSCs were transfected with linear polyethylenimine using a cpg-free plasmid encoding the transgene in the presence of a combination of fusogenic lipids and β tubulin deacetylase inhibitor (Enhancer). Process scalability was evaluated in various planar vessels and microcarrier-based bioreactor. The transfection efficiency was determined with flow cytometry, and the therapeutic efficacy of CD::UPRT::GFP expressing MSCs was evaluated in cocultures with temozolomide (TMZ)-sensitive or TMZ-resistant human glioblastoma cell lines. In the presence of 5-fluorocytosine (5FC), the 5-fluorouracil-mediated cytotoxicity was determined by performing colometric MTS assay. In vivo antitumor effects were examined by local injection into subcutaneous TMZ-resistant tumors implanted in the athymic nude mice.

Results

At > 90% transfection efficiency, the phenotype, differentiation potential and tumour tropism of MSCs were unaltered. High reproducibility was observed in all scales of transfection. The therapeutically modified MSCs displayed strong cytotoxicity towards both TMZ-sensitive and TMZ-resistant U251-MG and U87-MG cell lines only in the presence of 5FC. The effectiveness of this approach was further validated with other well-characterized and clinically annotated patient-derived GBM cells. Additionally, a long-term suppression (> 30 days) of the growth of a subcutaneous TMZ-resistant U-251MG tumour was demonstrated.

Conclusions

Collectively, this highly efficient non-viral workflow could potentially enable the scalable translation of therapeutically engineered MSC for the treatment of TMZ-resistant GBM and other applications beyond the scope of this study.
Hepatocyte-like cells derived from human induced pluripotent stem cells using small molecules: implications of a transcriptomic study
Authors: Gao Xiugong , Li Rong , Cahan Patrick , Zhao Yang , Yourick Jeffrey J. , Sprando Robert L.
Published: September 2020

Background

Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) hold great promise in toxicological applications as well as in regenerative medicine. Previous efforts on hepatocyte differentiation have mostly relied on the use of growth factors (GFs) to recapitulate developmental signals under in vitro conditions. Recently, the use of small molecules (SMs) has emerged as an attractive tool to induce cell fate transition due to its superiority in terms of both quality and cost. However, HLCs derived using SMs have not been well characterized, especially on the transcriptome level.

Methods

HLCs were differentiated from human iPSCs using a protocol that only involves SMs and characterized by transcriptomic analysis using whole genome microarrays.

Results

HLCs derived using the SM protocol (HLC_SM) displayed specific hepatic marker expression and demonstrated key hepatic functions. Transcriptomic analysis of the SM-driven differentiation defined a hepatocyte differentiation track and characterized the expression of some key marker genes in major stages of hepatocyte differentiation. In addition, HLC_SM were scored with CellNet, a bioinformatics tool quantifying how closely engineered cell populations resemble their target cell type, and compared to primary human hepatocytes (PHHs), adult liver tissue, fetal liver tissue, HLCs differentiated using GFs (HLC_GF), and commercially available HLCs. Similar to HLC_GF, HLC_SM displayed a mixed phenotype of fetal and adult hepatocytes and had relatively low expression of metabolic enzymes, transporters, and nuclear receptors compared to PHHs. Finally, the differentially expressed genes in HLC_SM compared to HLC_GF and to PHHs were analyzed to identify pathways and upstream transcription regulators which could potentially be manipulated to improve the differentiation of HLCs.

Conclusions

Overall, the present study demonstrated the usefulness of the SM-based hepatocyte differentiation method, offered new insights into the molecular basis of hepatogenesis and associated gene regulation, and suggested ways for further improvements in hepatocyte differentiation in order to obtain more mature HLCs that could be used in toxicological studies.
Disruption of zinc transporter ZnT3 transcriptional activity and synaptic vesicular zinc in the brain of Huntington’s disease transgenic mouse
Authors: Niu Li , Li Li , Yang Shiming , Wang Weixi , Ye Cuifang , Li He
Published: September 2020

Background

Huntington’s disease (HD) is a neurodegenerative disease that involves a complex combination of psychiatric, cognitive and motor impairments. Synaptic dysfunction has been implicated in HD pathogenesis. However, the mechanisms have not been clearly delineated. Synaptic vesicular zinc is closely linked to modulating synaptic transmission and maintaining cognitive ability. It is significant to assess zinc homeostasis for further revealing the pathogenesis of synaptic dysfunction and cognitive impairment in HD.

Results

Histochemical staining by autometallography indicated that synaptic vesicular zinc was decreased in the hippocampus, cortex and striatum of N171-82Q HD transgenic mice. Analyses by immunohistochemistry, Western blot and RT-PCR found that the expression of zinc transporter 3 (ZnT3) required for transport of zinc into synaptic vesicles was obviously reduced in these three brain regions of the HD mice aged from 14 to 20 weeks  and  BHK  cells  expressing  mutant  huntingtin. Significantly, dual-luciferase reporter gene and chromatin immunoprecipitation assays demonstrated that transcription factor Sp1 could activate ZnT3 transcription via its binding to the GC boxes in ZnT3 promoter. Moreover, mutant huntingtin was found to inhibit the binding of Sp1 to the promoter of ZnT3 and down-regulate ZnT3 expression, and the decline in ZnT3 expression could be ameliorated through overexpression of Sp1.

Conclusions

This is first study to reveal a significant loss of synaptic vesicular zinc and a decline in ZnT3 transcriptional activity in the HD transgenic mice. Our work sheds a novel mechanistic insight into pathogenesis of HD that mutant huntingtin down-regulates expression of ZnT3 through inhibiting binding of Sp1 to the promoter of ZnT3 gene, causing disruption of synaptic vesicular zinc homeostasis. Disrupted vesicular zinc ultimately leads to early synaptic dysfunction and cognitive deficits in HD. It is also suggested that maintaining normal synaptic vesicular zinc concentration is a potential therapeutic strategy for HD.
Eigenvalues of s-type operators on $C(p)$ equipped with a pre-quasi norm
Authors: Bakery Awad A. , Mohamed Elsayed A. E.
Published: September 2020

We investigate some new topological properties of the multiplication operator on$C(p)$C(p)defined by Lim (Tamkang J. Math. 8(2):213–220, 1977) equipped with the pre-quasi-norm and the pre-quasi-operator ideal formed by this sequence space ands-numbers.
On modeling of coronavirus-19 disease under Mittag-Leffler power law
Authors: Bushnaq Samia , Shah Kamal , Alrabaiah Hussam
Published: September 2020

This paper investigates a new model on coronavirus-19 disease (COVID-19) with three compartments including susceptible, infected, and recovered class under Mittag-Leffler type derivative. The mentioned derivative has been introduced by Atangana, Baleanu, and Caputo abbreviated as$(\mathcal{ABC})$(ABC). Upon utilizing fixed point theory, we first prove the existence of at least one solution for the considered model and its uniqueness. Also, some results about stability of Ulam–Hyers type are also established. By applying a numerical technique called fractional Adams–Bashforth (AB) method, we develop a scheme for the approximate solutions to the considered model. Using some real available data, we perform the concerned numerical simulation corresponding to different values of fractional order.
Diversity of antibiotics in hospital and municipal wastewaters and receiving water bodies and removal efficiency by treatment processes: a systematic review protocol
Authors: Ebrahimi Seyedeh Masoumeh , Dehghanzadeh Reyhani Reza , Asghari-JafarAbadi Mohammad , Fathifar Zahra
Published: September 2020

Background

Antibiotics are extensively discharged into the environment through sewages. These emergent contaminants cause health and environmental risks by toxicity, allergic impacts, non-biodegradability and more importantly advancing antibiotic resistance. Antibiotics are hardly removed by conventional treatment processes and frequently are being reported in aquatic environments. The systematic review outlined in this protocol will compile and synthesize literature on the variety and concentrations of antibiotics in wastewaters and receiving water resources. Also, the review will address the efficiency of treatment processes in elimination of antibiotics from aqueous solutions. Outcomes of the study could help wastewater treatment plant engineers with providing reliable design data and outline a road map for future researches.

Methods

The review will be performed according to the Collaboration for Environmental Evidence (CEE) guidelines for systematic review and evidence synthesis in environmental management, and will be reported according to ROSES reporting standards for systematic evidence syntheses. The published articles will be screened by considering the defined inclusion and exclusion criteria at the title, abstract and full-text levels. Included studies will be exposed to a critical appraisal for validity and quality assessment. The articles will be assessed on the susceptibility to bias and the studies with high bias will be excluded from the data synthesis. The data from included studies will be combined into a narrative synthesis. Random effect Meta-analysis will be conducted due to the likely range of underlying effects. If the heterogeneity exists, the source of heterogeneity will be sought by met-regression and subgroup analyses.
What are the effects of climate variability and change on ungulate life-histories, population dynamics, and migration in North America? A systematic map protocol
Authors: Malpeli Katherine C. , Weiskopf Sarah R. , Thompson Laura , Hardy Amanda R.
Published: September 2020

Background

Climate is an important driver of ungulate life-histories, population dynamics, and migratory behaviors, and can affect the growth, development, fecundity, dispersal, and demographic trends of populations. Changes in temperature and precipitation, and resulting shifts in plant phenology, winter severity, drought and wildfire conditions, invasive species distribution and abundance, predation, and disease have the potential to directly or indirectly affect ungulates. However, ungulate responses to climate variability and change are not uniform and vary by species and geography. Here, we present a systematic map protocol aiming to describe the abundance and distribution of evidence on the effects of climate variability and change on ungulate life-histories, population dynamics, and migration in North America. This map will help to identify knowledge gaps and clusters of evidence, and can be used to inform future research directions and adaptive management strategies.

Methods

We will catalogue evidence on how climate variability and change affect the life-histories, population dynamics, and migration patterns of the fifteen ungulate species native to North America. We will search both academic and grey literature, using academic journal databases and specialist websites. Articles will be screened for inclusion at the title/abstract and full-text levels, and data will be extracted from articles that pass the full-text review. These data will be summarized quantitatively, visually, and with a narrative review to describe the distribution and abundance of evidence on the effects of climate variability and change on ungulates in North America.
Identification of novel molecular markers of mastitis caused by Staphylococcus aureus using gene expression profiling in two consecutive generations of Chinese Holstein dairy cattle
Authors: Wang Di , Liu Lei , Augustino Serafino M. A. , Duan Tao , Hall Thomas J. , MacHugh David E. , Dou Jinhuan , Zhang Yi , Wang Yachun , Yu Ying
Published: September 2020

Background

Mastitis in dairy cows caused byStaphylococcus aureusis a major problem hindering economic growth in dairy farms worldwide. It is difficult to prevent or eliminate due to its asymptomatic nature and long persistence of infection. Although transcriptomic responses of bovine mammary gland cells to pathogens that cause mastitis have been studied, the common responses of peripheral blood leukocytes toS. aureusinfection across two consecutive generations of dairy cattle have not been investigated.

Methods

In the current study, RNA-Seq was used to profile the transcriptomes of peripheral blood leukocytes sampled fromS. aureus-infected mothers and theirS. aureus-infected daughters, and also healthy non-infected mothers and their healthy daughters. Differential gene expression was evaluated as follows: 1)S. aureus-infected cows versus healthy non-infected cows (S vs. H, which include all the mothers and daughters), 2)S. aureus-infected mothers versus healthy non-infected mothers (SM vs. HM), and 3)S. aureus-infected daughters versus healthy non-infected daughters (SMD vs. HMD).

Results

Analysis of all identified expressed genes in the four groups (SM, SMD, HM, and HMD) showed thatEPOR,IL9,IFNL3,CCL26,IL26were exclusively expressed in both the HM and HMD groups, and that they were significantly (P <  0.05) enriched for the cytokine-cytokine receptor interaction pathway. A total of 17, 13 and 10 differentially expressed genes (DEGs) (FDRPadj.< 0.1 and |FC| > 1.2) were detected in the three comparisons, respectively. DEGs withP <  0.05 and |FC| > 2 were used for functional enrichment analyses. For the S vs. H comparison, DEGs detected includedCCL20,IL13andMMP3, which are associated with the IL-17 signaling pathway. In the SM vs. HM and SMD vs. HMD comparisons, five (BLA-DQB,C1R,C2,FCGR1A, andKRT10) and six (BLA-DQB,C3AR1,CFI,FCAR,FCGR3A, andLOC10498484) genes, respectively, were involved in theS. aureusinfection pathway.

Conclusions

Our study provides insights into the transcriptomic responses of bovine peripheral blood leukocytes across two generations of cattle naturally infected withS. aureus. The genes highlighted in this study could serve as expression biomarkers for mastitis and may also contain sequence variation that can be used for genetic improvement of dairy cattle for resilience to mastitis.
The relationship of smartphone addiction with psychological distress and neuroticism among university medical students
Authors: Lei Leonard Yik-Chuan , Ismail Muhd Al-Aarifin , Mohammad Jamilah Al-Muhammady , Yusoff Muhamad Saiful Bahri
Published: September 2020

Background

Smartphone plays a vital role in higher education as it serves as a device with multiple functions. Smartphone addiction was reported on the rise among college and university students. The addiction may result in unwanted consequences on their academic performance and psychological health. One factor that consistently relates to psychological distress and smartphone addiction is the neurotic personality trait. This study explored the relationship of smartphone addiction with psychological health and neuroticism among USM medical students.

Methods

A cross-sectional study was carried out on medical students in a public medical school. DASS-21, the neuroticism-subscale of USMaP-i and SAS-SV were administered to measure psychological distress, neuroticism, and smartphone addiction of the medical students. Spearman correlation was performed to examine the correlation between smartphone addiction with psychological distress and neuroticism. Simple linear regression was performed to investigate relationship factors of smartphone addiction.

Results

A total of 574 medical students participated in this study. The prevalence of smartphone addiction was 40.6%. It was higher among male (49.2%) compared to female (36.6%) medical students. The result showed a fair positive correlation between smartphone addiction and psychological health (rdepression = 0.277, p-value < 0.001; ranxiety = 0.312, p-value < 0.001; rstress = 0.329, p-value < 0.001). However, there was a poor positive correlation between smartphone addiction and neuroticism (r = 0.173, p-value < 0.001). The simple linear regression showed a significant increase in the levels of depression, anxiety, stress and neuroticism upon one unit increase in smartphone addiction (bdepression = 0.101, p-value < 0.001; banxiety = 0.120, p-value < 0.001; bstress = 0.132, p-value < 0.001; bneuroticism = 0.404, p-value < 0.05). These results indicated significant relationships between smartphone addiction, psychological health and neuroticism.

Conclusion

This study suggested a high prevalence of smartphone addiction among medical students, particularly in male medical students. The smartphone addiction might lead to psychological problems and the most vulnerable group is the medical student with the neurotic personality trait.
Saline versus 5% dextrose in water as a drug diluent for critically ill patients: a retrospective cohort study
Authors: Aoyagi Yukari , Yoshida Takuo , Uchino Shigehiko , Takinami Masanori , Uezono Shoichi
Published: September 2020

Background

The choice of intravenous infusion products for critically ill patients has been studied extensively because it can affect prognosis. However, there has been little research on drug diluents in this context. The purpose of this study is to evaluate the impact of diluent choice (saline or 5% dextrose in water [D5W]) on electrolyte abnormalities, blood glucose control, incidence of acute kidney injury (AKI), and mortality.

Methods

This before-after, two-group comparative, retrospective study enrolled adult patients who stayed for more than 48 h in a general intensive care unit from July 2015 to December 2018. We changed the default diluent for intermittent drug sets in our electronic ordering system from D5W to saline at the end of 2016.

Results

We included 844 patients: 365 in the D5W period and 479 in the saline period. Drug diluents accounted for 21.4% of the total infusion volume. The incidences of hypernatremia and hyperchloremia were significantly greater in the saline group compared to the D5W group (hypernatremia 27.3% vs. 14.6%, p < 0.001; hyperchloremia 36.9 % vs. 20.4%, p < 0.001). Multivariate analyses confirmed the similar effects (hypernatremia adjusted odds ratio (OR), 2.43; 95% confidence interval (CI), 1.54–3.82; hyperchloremia adjusted OR, 2.09; 95% CI, 1.31–3.34). There was no significant difference in the incidences of hyperglycemia, AKI, and mortality between the two groups.

Conclusions

Changing the diluent default from D5W to saline had no effect on blood glucose control and increased the incidences of hypernatremia and hyperchloremia.
A low complexity heuristic to solve a learning objects recommendation problem
Authors: Falci Samuel Henrique , Dorça Fabiano Azevedo , Andrade Alessandro Vivas , Mourão Falci Daniel Henrique
Published: September 2020

The recommendation of learning objects in virtual learning environments has become the focus of research to improve online learning experience. Several approaches have been presented in an attempt to model the individual characteristics of the students and offer learning objects that best suit their particularities. Most of them, though, are impractical in real-world scenarios due to the high computational cost as a huge number of repositories offering learning objects such as Youtube, Wikipedia, Stackoverflow, Github, discussion forums, social networks and many others are available and each has a large amount of learning objects that can be retrieved. In this work, we propose a low complexity heuristic to solve this problem, comparing it to a classical mixed-integer linear programming model and classical genetic algorithm in varying dataset sizes that contain from 2000 to 1360000 learning objects. Performance and optimality were analyzed. The results showed that the proposed technique was only slightly suboptimal, while its computational cost was considerably smaller than the one presented by the linear optimization approach.
Spatiotemporal behavior of a large-scale landslide at Mt. Onnebetsu-dake, Japan, detected by three L-band SAR satellites
Authors: Takada Youichiro , Motono George
Published: September 2020

We applied differential InSAR analysis to the Shiretoko Peninsula, northeastern Hokkaido, Japan. All the interferograms of long temporal baseline (~ 3 years) processed from SAR data of three L-band satellites (JERS-1, ALOS, ALOS-2) commonly indicate remarkable phase changes due to the landslide movement at the southeastern flank of Mt. Onnebetsu-dake, a Quaternary stratovolcano. The area of interferometric phase change matches to known landslide morphologies. Judging from the timing of the SAR image acquisitions, this landslide has been moving at least from 1993 to the present. Successive interferograms of 1-year temporal baseline indicate the temporal fluctuation of the landslide velocity. Especially for the descending interferograms, the positive line-of-sight (LOS) length change, which indicates large subsidence relative to the horizontal movement, is observed in the upslope section of the landslide during 1993–1998, while the negative LOS change is observed in the middle and the downslope section after 2007 indicating less subsidence. The landslide activity culminates from 2014 to 2017: the eastward and the vertical displacement rates reach ~ 6 and ~ 2 cm/yr, respectively. Utilizing high spatial resolution of ALOS and ALOS-2 data, we investigated velocity distribution inside the landslide. During 2007–2010, the eastward component of surface displacement increases toward the east, implying that the landslide extends toward the east. During 2014–2017, the vertical displacement profile exhibits spatially periodic uplift and subsidence consistent with surface gradient, which indicates the ongoing deformation driven by gravitational force. Heavy rainfall associated with three typhoons in August 2016 might have brought about an increase in the landslide velocity, possibly due to elevated pore-fluid pressure within and/or at the base of the landslide material. Also, annual rainfall would be an important factor that prescribes the landslide velocity averaged over 3 years.
A mock circulation loop to test extracorporeal CO2 elimination setups
Authors: Schwärzel Leonie S. , Jungmann Anna M. , Schmoll Nicole , Seiler Frederik , Muellenbach Ralf M. , Schenk Joachim , Dinh Quoc Thai , Bals Robert , Lepper Philipp M. , Omlor Albert J.
Published: September 2020

Background

Extracorporeal carbon dioxide removal (ECCO2R) is a promising yet limited researched therapy for hypercapnic respiratory failure in acute respiratory distress syndrome and exacerbated chronic obstructive pulmonary disease. Herein, we describe a new mock circuit that enables experimental ECCO2R research without animal models. In a second step, we use this model to investigate three experimental scenarios of ECCO2R: (I) the influence of hemoglobin concentration on CO2removal. (II) a potentially portable ECCO2R that uses air instead of oxygen, (III) a low-flow ECCO2R that achieves effective CO2clearance by recirculation and acidification of the limited blood volume of a small dual lumen cannula (such as a dialysis catheter).

Results

With the presented ECCO2R mock, CO2removal rates comparable to previous studies were obtained. The mock works with either fresh porcine blood or diluted expired human packed red blood cells. However, fresh porcine blood was preferred because of better handling and availability. In the second step of this work, hemoglobin concentration was identified as an important factor for CO2removal. In the second scenario, an air-driven ECCO2R setup showed only a slightly lower CO2wash-out than the same setup with pure oxygen as sweep gas. In the last scenario, the low-flow ECCO2R, the blood flow at the test membrane lung was successfully raised with a recirculation channel without the need to increase cannula flow. Low recirculation ratios resulted in increased efficiency, while high recirculation ratios caused slightly reduced CO2removal rates. Acidification of the CO2depleted blood in the recirculation channel caused an increase in CO2removal rate.

Conclusions

We demonstrate a simple and cost effective, yet powerful, “in-vitro” ECCO2R model that can be used as an alternative to animal experiments for many research scenarios. Moreover, in our approach parameters such as hemoglobin level can be modified more easily than in animal models.
Prevalence, antimicrobial susceptibility pattern, and associated factors of Salmonella and Shigella among food handlers in Adigrat University student’s cafeteria, northern Ethiopia, 2018
Authors: Legese Haftom , Kahsay Tsega , Gebrewahd Aderajew , Berhe Brhane , Fseha Berhane , Tadesse Senait , Gebremariam Guesh , Negash Hadush , Mardu Fitsum , Tesfay Kebede , Adhanom Gebre
Published: September 2020

Background

Food handlers play a significant role in the transmission of foodborne infections.SalmonellaandShigellaare the most common foodborne pathogens and their infections are a major public health problem globally. Thus, this study aimed to determine the prevalence, antimicrobial susceptibility patterns, and associated factors ofSalmonellaandShigellacolonization among food handlers.

Methodology

A cross-sectional study was conducted from March to August 2018 at Adigrat University student cafeteria, Northern Ethiopia. Data on socio-demographic and associated factors were collected using a structured questionnaire. Fresh stool samples were collected from 301 food handlers and transported to Adigrat University Microbiology Laboratory. Bacterial isolation and antimicrobial susceptibility test were performed using standard bacteriological methods. Data analysis was performed using SPSS version 22 andP < 0.05 where a corresponding 95% confidence interval was considered statistically significant.

Results

A total of 301 food handlers were included in this study. The majority of study participants were females 265 (88.0%). About 22 (7.3%) and 11 (3.7%) of food handlers were found to be positive forSalmonellaandShigellarespectively. Hand washing after using a bathroom with water only, no hand washing after using the bathroom, no hand washing after touching dirty materials, no hand washing before food handling, and untrimmed fingernails were significant associated factors identified. None of theSalmonellaandShigellaisolates were sensitive to ampicillin, yet low resistance against chloramphenicol, ceftriaxone, and ciprofloxacin was found.

Conclusion

The present study revealed that the prevalence ofSalmonellaandShigellaamong food handlers was 22 (7.3%) and 11 (3.7%) respectively. Such colonized food handlers can contaminate food, and drinks and could serve as a source of infection to consumers. This indicates that there is a need for strengthened infection control measures to preventSalmonellaandShigellatransmission in the students’ cafeteria.