bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Small Molecular Compounds on Properties of Fibroblast in Chuan Snub-nosed Monkey
Authors: wang juanjuan , liu xin , yang jing , guo hanxing , li jingjing , huo lihui , zhao haitao , wang xiaowei , yan xingrong , li baoguo
Published: March 2021

Small molecular compounds could improve the induction efficiency of induced pluripotent stem cells (iPS). To investigate their effects on the efficiency of interspecies nuclear transfers, fibroblasts from the Chuan snub-nosed monkey were treated with small molecular compounds and used as donor cells to be injected into the enucleated oocytes of a goat. The gene expression profiles in the cell-constructed embryos, with and without the small molecular compound treatments, were determined by qPCR. Results showed that the cell morphology showed obvious changes, while the gene expression profiles of the fibroblasts were altered by the treatment. The pluripotent genes (Oct4, sox2, and nanog) were significantly increased on treatment with the small molecular compounds. Results demonstrated that these small molecular compounds could alter the properties of the donor cells, to promote the expression levels of the pluripotent genes for the Chuan golden-goat interspecies embryo, which would provide references for conservation of Chuan snub-nosed monkey.
The Baseline Characteristics of Patients with COVID-19 and Impact of Various Risk Factors on the Outcome of Patients Admitted in Tertiary Care Hospital.
Authors: Shaikh Samiullah , Deedar Faiza , Devrajani Tara Chand
Published: March 2021

Background: The outbreak caused by novel coronavirus was first reported in Wuhan, China in December 2019 when a new pathogen was discovered from the bronchoalveolar lavage fluid of the patient suffering from pneumonia. Globally over 81.47 million confirmed cases and 1.79 million deaths has been reported. The clinical spectrum ranges from mild influenza-like illness to severe life threatening respiratory disease requiring ventilatory support to death. The purpose of this study was to evaluate the baseline carecteristic of the patients and impact of various risk factors on the outcome of patients admitted in tertiary care hospital. MATERIALS AND METHODSStudy Area and Period: This study was conducted at Liaquat University Hospital from April 2020 to September 2020. Study Design: Cross-Sectional Descriptive.Inclusion Criteria: The patients were included on the basis of diagnosis of COVID-19 confirmed on reverse transcription Polymerase Chain reaction (RT-PCR) test. Categorical variables such as age, sex, Gram-Covid risk category ,diabetes mellitus, hypertension, renal, pulmonary disease, obesity, outcome of patient were presented as frequency and percentage RESULTS: This study included 235 consecutive patients admitted at Liaquat University Hospital from April 2020 to September 2020. There were 187(79.6%) male and 48(20.4 %) female. The age < 65 years were present in 80 ( 34%) and ≥ 65 155(66%) patients. The most prevalent symptoms were fever ,breathlessness, cough, anorexia, fatigue in all 235(100% ) patients. Severity of illness according to Gram-Covid Score 18 (7.7%) patients were in low-risk group, 93(39.6%) in moderate risk group and 124 (52.8%) in High risk group.There were no risk factors in 121(51.5%) , one risk factor in 49(20.9%), two risk factors in32(13.6%) , three risk factors in 18( 7.7%) and four risk factors in 15(6.4%) patients.The outcome of patients showed 57(24.3%) deaths, 107 (45.5%) patients had prolong stay and 71(30.2%) patients recovered. A strong relationship was observed between the outcome of patient with age, number of risk factors, severity of illness according to gram - Covid score whereas insignificant relationship with the sex of patients.Conclusion: COVID-19 patients clinically present with fever, cough and breathlessness. Majority of patients present with moderate to high severity. Patient with advanced age, high risk on gram-Covid score with multiple comorbidities are particularly susceptible to adverse outcome.
WITHDRAWN: Diagnostic and Therapeutic Challenges in The Management of Acute Massive Overt Bleeding of Jejunal Gastrointestinal Stromal Tumours: Case Series
Authors: NAGARAJ SATISH SUBBIAH , Deivasigamani Sriram , Aruni Amresh , Kumar Hemanth , Sachan Anurag , Samanta Jayanta , Bal Amanjit
Published: March 2021

Introduction:
Jejunal Gastro-Intestinal Stromal Tumours (GIST) are rare mesenchymal tumours. Acute massive overt bleeding from jejunal GIST are very rare and poses both diagnostic and therapeutic challenges in emergent conditions.
Methods
A case series with retrospective analysis of prospectively maintained database of patients presenting with acute massive overt bleeding secondary to histologically proven jejunal GIST was done. Clinical characteristics, endoscopic and imaging diagnostic features, histological findings, surgical procedures and outcomes in these patients were studied.
Results
Three patients were included in this case series. Mean age of presentation was 49.0 years with two male and one female patient. All three patients presented with melena and hemodynamic instability, resuscitated with adequate blood transfusions. Routine endoscopic assessment were inconclusive. Multiphasic Computed Tomographic Angiography (CTA) revealed hypodense hypervascular mass in jejunum in all three patients. One patient was unresponsive to blood transfusion and underwent emergency exploratory laparotomy. One patient underwent laparoscopic resection and reconstruction. Mean length of hospital stay was 5.3 days. Histopathological examination confirmed Jejunal GIST in all three patients with microscopically negative resection margins. Two patients were disease free till 18 months follow up and the one patient lost to follow up after 1 year.
Conclusion
Multiphasic CTA is a single step diagnostic tool for localisation of bleed and assessment of tumour characteristics in emergent conditions. Surgical resection is the mainstay of treatment for both control of bleed and to provide oncologically clear resection margins.
Diagnostic Accuracy of the Screening Instruments Used to Identify Postpartum Depression in the Primary Care Setting: Protocol for a Systematic Review and Meta-Analysis
Authors: Andriani Russy Novita , Makkiyyah Siti Solichatul , Hertika Amanda Safira Dea , Istiono Wahyudi , Hakimi Mohammad
Published: March 2021

Background
Postpartum depression (PPD) is a prevalent complication of pregnancy, this condition affects maternal and child well-being and functioning. Results from a meta-analysis showed an incidence of 13% PPD cases in the first 12 weeks after labor. Primary care is the first gate and continuing point of care for patients. Despite the controversy of screening and early identification in primary care settings, many PPD cases remain undetected. Given the uncertainty about this issue, screening instruments must be effective in identifying the cases. This systematic review and meta-analyses aim to identify the most suitable postpartum depression screening instrument for use in primary care.
Methods
PubMed, ScienceDirect, and ProQuest databases were used to search using relevant keywords or MeSH, with limitation of publication from January 1st, 2010 through December 31st, 2020. We will include screening studies on postpartum women using validated screening tools followed by validated structured or semi-structured interview for Diagnostic and Statistical Manual of Mental Disorders (DSM) as the reference standard in the primary care setting. Study designs included in the review are cross-sectional and randomized controlled trial without no screening arm on the diagnostic study. We will use a liberal accelerated method on the title and abstract review stage, then perform full-text article reviews on selected studies. Methodological quality will be assessed independently by two authors according to QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). Extraction of the study data will be undertaken by one reviewer and checked by a second reviewer. Disagreements will be resolved by consensus and including a third investigator as necessary. The test characteristics will be extracted into 2x2 tables for all included studies. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots.
Discussion
The proposed systematic review and meta-analyses will allow us to obtain the most suitable postpartum depression screening instrument for use in primary care.
Systematic review registration:
PROSPERO CRD42020216067
Bedding Effect of Carbonaceous Slate Failure Behavior at Direct Shear Tests
Authors: Wang Han , Ren Fuqiang , Chang Yuan
Published: March 2021

In this study, the carbonaceous slate of Muzhailing tunnel was selected to explore the deformation and failure mechanism of tunnel layered slate under direct shear conditions. Five sets of direct shear tests were carried out on slate with different bedding dip angles (β: 0°, 30°, 45°, 60°, and 90°). The strength parameters, failure mode, fracture topography, dissipated energy, and acoustic emission (AE) characteristics were analyzed in detail to study the bedding effect of slate failure. The results show that the cohesion and internal friction angle of slate increases and decreases linearly with β from 0° to 90°, respectively, and the shear strength of bedding plane is lower than that of matrix. Additionally, the relative roughness (δ) of gray-scale image was defined, and the linear relationship between δ and root-mean-square height (Sq) was established to improve the efficiency of evolution of fracture topography. Furthermore, the shear energy consumption per unit area (us) was calculated, less sensitive to the variation of β. Moreover, a larger AE count and energy release rate were observed when the shear stress decreased, and a relative quiet period was observed before the peak loading. Additionally, both the count and energy release rate linearly decreased with the increase in β, and the proportion of tensile microcracks for vertical bedding is slightly higher than that for horizontal bedding. The main frequency of vertical bedding slate is smaller than that of horizontal bedding, i.e., the size of microcracks of slate with β of 90° is relatively larger. Generally, the frequency bandwidth of slate became narrower when β was varied from 30° to 60°, and the main frequency increased, indicating that the degree of shear failure of matrix is weakened. In contrast, the degree of cracking along the bedding plane increased.
Cardiorespiratory Monitoring of Red Blood Cell Transfusion in Preterm Infants
Authors: Poppe Jarinda A. , Essen Tanja van , Weteringen Willem van , Willemsen Sten P. , Reiss Irwin K.M. , Simons Sinno H.P. , Jonge Rogier C.J. de
Published: March 2021

Clinical improvement after red blood cell (RBC) transfusions in preterm infants remains debated. This study aims to investigate the effect of RBC transfusion on the occurrence of desaturations and hypoxia and other cardiorespiratory outcomes in preterm infants. In this longitudinal observational study, prospectively stored cardiorespiratory parameters of preterm infants who received at least one RBC transfusion between July 2016 and June 2017 were analyzed. Sixty infants with 112 RBC transfusions, median GA of 26.7 weeks, were included. The number of desaturations and area <80% SpO2 limit, as a measure of the hypoxic burden, were calculated in 24h before and after RBC transfusion. A mixed effects model was used to account for repeated measurements. Overall, mean (SE) number of desaturations per hour decreased from 3.28(0.55) to 2.25(0.38; p<0.001) and area <80% SpO2 limit decreased from 0.14(0.04) to 0.08(0.02) %/sec (p=0.02). These outcomes were stratified for number of desaturations in 24h prior to RBC transfusion. The largest effect was observed in the group with the highest mean number of desaturations (≥6) prior to RBC transfusion, with a decrease from 7.50(0.66) to 4.26(0.38) (p<0.001) in number of desaturations and 0.46(0.13) to 0.20(0.06) in area <80% SpO2. Perfusion index increased significantly after RBC transfusion (p<0.001). No other significant effects of RBC transfusion on cardiorespiratory data were observed.Conclusions: RBC transfusions in preterm newborns decrease the incidence of desaturations and the hypoxic burden. The higher the number of desaturations prior to the RBC transfusion, the larger the effect observed.
Medication incidents and pharmacist interventions in relation to directly acting oral anticoagulants in hospital settings: evaluation using Reason’s Accident Causation Theory
Authors: Haque Hazera , Alrowily Abdulrhman , Jalal Zahraa , Tailor Bijal , Efue Vicky , Sarwar Asif , Paudyal Vibhu
Published: March 2021

BackgroundDirect oral anticoagulants (DOACs) have revolutionised anticoagulant pharmacotherapy. However DOACs medication incidents are known to be common.ObjectiveTo assess medication incidents associated with DOACs using an error theory and to analyse pharmacists’ contributions in minimising medication incidents in secondary care settings.SettingA large University tertiary academic hospital in the West Midlands of England.MethodsMedication incident data from the incident reporting system (48-months period) and pharmacist interventions data from the prescribing system (26-month period) were extracted. Reason’s Accident Causation Model was used to identify potential causality of the incidents. Pharmacists’ intervention data was thematically analysed.Main outcome measure(a) Frequency, type and potential causality of DOACs incidents, (b) Nature of pharmacists’ interventions.ResultsA total of 812 DOACs reports were included in the study (124 medication incidents and 688 intervention reports). Missing drug/omission was the most common incident type (26.6%,n = 33) followed by wrong drug (16.1%,n = 20) and wrong dose/strength (11.3%,n = 14). A high majority (89.5%,n = 111) of medication incidents were caused by active failures. Patient discharge without anticoagulation supply and failure to restart DOACs post procedure/scan were commonly recurring themes. The majority of (38.1%,n = 262) the pharmacist interventions were related to pharmacological strategy (i.e., drug or dose changes or discontinuation). Impaired renal function was the most common reason for dose adjustments.ConclusionPrescribers’ active failure rather than system errors (i.e. latent failures) are contributing to DOACs incidents. Rreinforcement of guideline adherence, prescriber education, harnessing pharmacists’ roles and mandating renal function information in prescriptions are likely to improve patient safety.
G Protein-Coupled Receptor Kinase 3 Modulates Mesenchymal Stem Cell Proliferation and Differentiation Through Sphingosine-1-Phosphate Receptor Regulation
Authors: Brozowski Jaime , Timoshchenko Roman , Serafin Donald Stephen , Allyn Brittney , Koontz Jessica , Rabjohns Emily , Ren Yinshi , Eudy Amanda , Harris Taylor F. , Abraham David , Mattox Daniel , Rubin Clinton T , Hilton Matthew , Rubin Janet , Allbritton Nancy , Billard Matthew , Tarrant Teresa
Published: March 2021

Background The bone marrow niche supports hematopoietic cell development through intimate contact with multipotent stromal mesenchymal stem cells; however, the intracellular signaling, function, and regulation of such supportive niche cells are still being defined. Our study was designed to understand how G protein receptor kinase 3 (GRK3) affects bone marrow mesenchymal stem cell function by examining primary cells from GRK3-deficient mice, which we have previously published to have a hypercellular bone marrow and leukocytosis through negative regulation of CXCL12/CXCR4 signaling. Methods Murine GRK3-deficient bone marrow mesenchymal stromal cells were harvested and cultured to differentiate into three lineages (adipocyte, chondrocyte, and osteoblast) to confirm multi-potency and compared to wild type cells. Immunoblotting, modified-TANGO experiments, and flow cytometry were used to further examine the effects of GRK3 deficiency on bone marrow mesenchymal stromal cell receptor signaling. Microcomputed tomography was used to determine trabecular and cortical bone composition of GRK3-deficient mice and standard ELISA to quantitate CXCL12 production from cellular cultures.Results GRK3-deficient, bone marrow-derived mesenchymal stem cells exhibit enhanced and earlier osteogenic differentiation in vitro. The addition of a sphingosine kinase inhibitor abrogated the osteogenic proliferation and differentiation, suggesting sphingosine-1-phosphate receptor signaling was a putative G-protein coupled receptor regulated by GRK3. Immunoblotting showed prolonged ERK1/2 signaling after stimulation with sphingosine-1-phosphate in GRK3-deficient cells, and modified-TANGO assays suggested the involvement of β-arrestin-2 in sphingosine 1 phosphate receptor internalization. Conclusions Our work suggests that GRK3 regulates sphingosine-1-phosphate receptor signaling on bone marrow mesenchymal stem cells by recruiting β-arrestin to the occupied GPCR to promote internalization, and lack of such regulation affects mesenchymal stem cell functionality.
Dynamic Modeling and Experimental Research on Position-dependent Behavior of Twin Ball Screw Feed System
Authors: Duan Meng , Lu Hong , Zhang Xinbao , Li Zhangjie , Zhang Yongquan , Yang Minghui , Liu Qi
Published: March 2021

To establish the dynamic model of machine tool structure is an important means to assess the performance of the machine tool structure during the cutting process. It’s necessary to study the dynamics of the machine tools in different configurations for the sake of analyzing the dynamic behavior of the machine tools in the entire workspace. In this paper, a robust approach is presented to build an efficient and reliable dynamic model to evaluate the position-dependent dynamics of the twin ball screw (TBS) feed system. First, the TBS feed system is divided into several components and a finite element (FE) model is built for each component. Second, the Craig-Bampton method is proposed to reduce the order of the substructures. Third, a multipoint constraints (MPCs) method was introduced to model the mechanical joints substructures of the TBS system, and the spring-damper element (SDE) is employed to connect the condensation nodes. Finally, a series experimental tests and full order FE analysis are conducted on the self-designed TBS worktable in the four positions to validate the effectiveness of the proposed dynamic model. The results show that the proposed approach evaluates accurately the position-dependent behavior of the TBS system.
In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration
Authors: Hytönen Marjo K , Sarviaho Riika , Jackson Christopher B , Syrjä Pernilla , Jokinen Tarja , Matiasek Kaspar , Rosati Marco , Dallabona Cristina , Baruffini Enrico , Quintero Ileana , Arumilli Meharji , Monteuuis Geoffray , Donner Jonas , Anttila Marjukka , Suomalainen Anu , Bindoff Laurence A , Lohi Hannes
Published: March 2021

We investigated the clinical, genetic, and pathological characteristics of a previously unknown severe juvenile brain disorder in several litters of Parson Russel Terriers. The disease started with epileptic seizures at 6 to 12 weeks of age and progressed rapidly to status epilepticus and death or euthanasia. Histopathological changes at autopsy were restricted to the brain. There was severe acute neuronal degeneration and necrosis diffusely affecting the grey matter throughout the brain with extensive intraneuronal mitochondrial crowding and accumulation of amyloid-β (Aβ). Combined homozygosity mapping and genome sequencing revealed an in-frame 6-bp deletion in the nuclear-encoded pitrilysin metallopeptidase 1 (PITRM1) encoding for a mitochondrial protease involved in mitochondrial targeting sequence processing and degradation. The 6-bp deletion results in the loss of two amino acid residues in the N-terminal part of PITRM1, potentially affecting protein folding and function. Assessment of the mitochondrial function in the affected brain tissue showed a significant deficiency in respiratory chain function. The functional consequences of the mutation were modeled in yeast and showed impaired growth in permissive conditions and an impaired respiration capacity. Loss-of-function variants in human PITRM1 result in a childhood-onset progressive amyloidotic neurological syndrome characterized by spinocerebellar ataxia with behavioral, psychiatric and cognitive abnormalities. Homozygous Pitrm1-knockout mice are embryonic lethal, while heterozygotes show a progressive, neurodegenerative phenotype characterized by impairment in motor coordination and Aβ deposits. Our study describes a novel early-onset PITRM1-related neurodegenerative canine brain disorder with mitochondrial dysfunction, Aβ accumulation, and lethal epilepsy. The findings highlight the essential role of PITRM1 in neuronal survival and strengthen the connection between mitochondrial dysfunction and neurodegeneration.
Depletion of Essential Fatty Acids in Muscle Is Associated With Shorter Survival of Cancer Patients Undergoing Surgery
Authors: Bhullar Amritpal S. , Rivas-Serna Irma Magaly , Anoveros-Barrera Ana , Dunichand-Hoedl Abha , Bigam David , Khadaroo Rachel G. , McMullen Todd , Bathe Oliver , Putman Charles T. , Baracos Vickie , Clandinin Michael T. , Mazurak Vera C.
Published: March 2021

Background: Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in membrane of blood plasma and serum in humans, however the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients.Methods: Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acid content of the muscle. Cut-points for fatty acids were established using optimal stratification.Results: Median survival was between 450-500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid above the cut-point compared to 720-800 days for patients below. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11-10.87), p=0.03], EPA [HR 3.92 (1.1-14.0), p=0.04] and DHA [HR 4.08 (1.1-14.6), p=0.03] when adjusted for sex. Conclusion: Lower amount of essential fatty acids in skeletal muscle membrane is predictor of survival in cancer patients. These results warrant investigation to restore depletion of bioactive fatty acids in cancer.
NSrp70 suppresses metastasis in
triple-negative breast cancer by modulating Numb/TβR1/EMT axis
Authors: Zhao Yang , Sun Hefen , Zhao Yuanyuan , Liu Qiqi , Liu Yang , Hou Yifeng , Jin Wei
Published: March 2021

Metastasis is a major cause of death in individuals suffering from triple-negative breast cancer. Alternative splicing of mRNA precursor allows cancer cells to create different protein isoforms which may promote metastasis. Quantitative proteomic analysis of primary and metastatic breast cancer cells revealed that nuclear speckle-related protein 70 (NSrp70) was significantly downregulated in highly metastatic cells. Downregulation of NSrp70 promoted the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that NSrp70 inhibited the skipped exon alternative splicing of NUMB, promoted the degradation of TGF-beta receptor 1(TβR1) through lysosome pathway, and regulated TGFβ/SMAD-mediated epithelial-mesenchymal transition (EMT) phenotype in breast cancer cells. Furthermore, high NSrp70 expression correlated with better prognosis in breast cancer patients. Our findings revealed that splicing regulator NSrp70 may serve as a metastasis suppressor.
Controlled Release of Acetyl Salicylic Acid in Intelligent Hydrogel Based on Cross-linked O-Carboxymethyl Chitosan
Authors: Wu Yiguang , Rajoka Muhammad Shahid Riaz , Zeng Jun , Mehwish Hafiza Mahreen , Liu Wenli , Zhao Liqing
Published: March 2021

Drug-loading hydrogels were prepared from O-carboxymethyl chitosan (O-CMCS) with a high degree of substitution and different deacetylation degree (DD) using acetylsalicylic acid as drug and glutaraldehyde as a cross-linking agent. Also, the DD’s effect on the controlled drug release performance of drug-loading particle was explored. The results showed that the hydrogels and particles were prepared from 5 g of O-CMCS solution (4.0 wt.%), 2.5 g of sodium acetylsalicylate solution (8.0 wt.%), and 1.5 mL of glutaraldehyde solution (1.0 wt.%). The interior pore size of the particle (DD = 51%) was between 50 and 100µm, and its cumulative drug release ratios in the simulated gastric and intestinal juices were of the top values. The drug release of the drug-loading particle was proved to be obviously pH sensitive and it can be applied as a colonic drug.
Study on Surface Evenness of Super-high-thickness Cutting in High-speed Wire Electrical Discharge Machining
Authors: Deng Cong , Liu Zhidong , Zhang Ming , Pan Hongwei , Qiu Mingbo
Published: March 2021

Surface machined by high-speed wire electrical discharge machining (HS-WEDM) at super-high thickness (more than 1000 mm) cutting suffers from uneven surface, a major problem that has been investigated in this paper. According to the analysis, as wire frame span increases, the rigidity of the wire electrode decreases, and under the action of discharge explosive force, wire electrode vibration intensifies. As a result, the machining stability inevitably decreases. However, the core problem is whether there is enough working fluid in the slit to dampen and absorb the vibration of the wire electrode so as to ensure the positional stability of the wire electrode. To verify the above point of view: first, the wire guide and gravity take-up with bidirectional tension in the wire feeding system were installed to improve the positional accuracy of the wire electrode; second, to improve the flow of the working fluid into the slit, the slit width was increased by improving the working fluid and a medium carrier with a higher melting point and vaporization point can reduce the vaporization of the working fluid in the slit as much as possible. The experiment showed that the outlet flow of the improved working fluid is 56.72% higher than that of the original working fluid when cutting a 750 mm thick workpiece, which increases the damping and vibration absorption effect of the working fluid on the wire electrode in the long and narrow gap. After the above measures were implemented, super-high thickness cutting can be carried out continuously and steadily, the surface evenness was significantly improved, and the workpiece with a thickness of 2000 mm was cut successfully.
Animal Source Food Eating Habits of Outpatients With Antimicrobial Resistance in Bukavu, D.R. Congo
Authors: Kashongwe Olivier Basole , Ngaruka Bilamirwa Reagan , Neema Sarcelles Bora Brigitte , Mitima Theophile Kashosi , Kishabongo Antoine Sadiki
Published: March 2021

Background: Antibiotic resistance is a public health concern in Democratic Republic Congo and worldwide. It is usually caused by antibiotic over prescription or dispensing practices. The consumption of animal source food (ASF) could be another source of antibiotic resistance but is rarely studied. The objective of the study was to evaluate the eating habits of ASF by outpatients with antimicrobial resistance through an analysis of (i) the association of their antimicrobial resistance with ASF consumption; (ii) the influence of the types of ASF on their antimicrobial resistance.Methods: This is a retrospective analytical study conducted at three major Hospitals in Bukavu City (D. R. Congo). A total number of 210 patients, whose samples (mainly faeces and urine) had been subjected to bacterial examination, was included in this study. Morphological, biochemical and antibiotic susceptibility (using disc diffusion method) tests were performed on the samples. This served to isolate and identify resistant bacteria. Afterwards, patients responded to questions about the types and quantity of ASF eaten in the last week. We analysed data using descriptive statistics, logistic regression and non-parametric ranking tests.Results: Escherichia coli (37.1%), Klebsiella pneumonae (14.7%), and Staphylococcus aureus (13.8%) were the most prevalent bacteria. E. coli (68.4%) and K. pneumonae (87.5%) were multidrug resistant (MDR), while S. aureus (7.7%) was minor. Low beef (O.R. 0.737, C.I. 0.542-1.002) and pork (O.R. 0.743, C.I. 0.560 – 0.985) consumption led to significantly (p<0.05) lower risks of resistance to ciprofloxacin. Patients eating three different ASF per week had the highest resistance score (20.67) and high consumption rates of goat meat, pork and milk (41.5%). Conclusion: The findings of this study suggest a contribution of human nutrition to antimicrobial resistance frequency. Our results show the existence of a high prevalence of multi-drug resistant bacteria in patients frequently consuming ASF in Bukavu. Therefore, a stricter control of antibiotic usage in livestock production and of their presence in ASF is recommended.
Awareness of basic life support among undergraduate medical students in Syria, Iraq and Jordan: a cross sectional study
Authors: Shashaa Mohammad Nour , Alkarrash Mohamad Shadi , Kitaz Mohammad Nour , Rhayim Roaa , Ismail Mohammed , Koumakli Hamzeh , Alhisah Nour , Al-Haider Ahmed , Al-salloum Samer
Published: March 2021

Background

Sudden cardiac arrest considers one of the most leading cause for death in all over the world. It is important for all medical students to train basic life support. This study evaluated the awareness of basic life support among medical students.
Methods

An electronic questionnaire based cross sectional study was conducted in November 2020 among 2114 medical student in Syria, Iraq and Jordan. We evaluated BLS skills according to mean score. A chi-squared test was used to determine if there were differences between those who attended a basic life support course and those who did not.
Results

1656 of the participants (78.3%) stated that they did not attend a basic life support course. There was a significant difference between the participants from different countries where the mean score in Syria, Jordan and Iraq was 18.3, 24.3 and 18.8 respectively (p < 0.05). The participants were divided into 3 level according to total score; low (0–12), moderate (13–24) and high (25–37). In total, 18.3%, 72.8% and 8.9% of participants had high, intermediate and low level respectively.
Conclusions

The overall knowledge of basic life support among medical students is not adequate and need significant improvements. This study showed that an attendance a basic life support course previously had an effect on knowledge level. Hence, there is an urgent need to apply basic life support courses into the pre-clinical stage at universities.
Titanium dioxide induces apoptosis under UVA irradiation via the generation of lysosomal membrane permeabilization-dependent reactive oxygen species in HaCaT cells
Authors: Kim In Young , Lee Tae Geol , Reipa Vytas , Heo Min Beom
Published: March 2021

Background Titanium dioxide nanoparticles (TiO2 NPs) are important nanomaterials with wide commercial applications. While the small size of TiO2 NPs is useful in various applications, their biosafety should be evaluated further. In this study, we investigated the cytotoxicity of TiO2 NPs in the presence and absence of UVA irradiation in human keratinocyte HaCaT cells.Results TiO2 NPs did not significantly affect cell viability in the absence of UVA irradiation. However, UVA-irradiated TiO2 NPs induced caspase-dependent apoptosis. Exposure of HaCaT cells to TiO2 NPs and UVA resulted in reactive oxygen species (ROS) generation, and lysosomal membrane permeabilization (LMP); both effects were absent without UVA irradiation. An analysis of the relationship between LMP and ROS, using CA-074 as a cathepsin inhibitor or NAC as an antioxidant, showed that LMP stimulates ROS generation under these conditions.Conclusion These results imply that LMP-dependent oxidative stress plays a critical role in the UVA phototoxicity of TiO2 NPs in HaCaT cells.
Resveratrol suppresses malignant progression of oral squamous cell carcinoma cells by inducing the ZNF750 pathway
Authors: Duan Yanjun , Wang Yongjie , Yin Xiaojia , Xiao Yue
Published: March 2021

Deletion or mutation of zinc finger protein 750 (ZNF750) has been linked to oral squamous cell carcinoma (OSCC), but it is not clear whether ZNF750 is a therapeutic target for OSCC. This study examined whether activation of zinc finger protein 750 (ZNF750) pathway may be involved in the ability of resveratrol to inhibit malignant progression of CAL-27 oral squamous cell carcinoma cells. CAL-27 cells were treated with resveratrol and transfected with plasmids expressing a ZNF750 mimic or ZNF750 inhibitor. Cell proliferation was assessed using the CCK-8 assay and a BrdU ELISA, and cell cycle distribution and apoptosis were examined using flow cytometry. Colony formation was also assessed. Western blotting was used to examine the effects of resveratrol on levels of angiogenin, vascular endothelial growth factor (VEGF), prolyl hydroxylase 2 (PHD2), G protein signal-regulated protein 5 (RGS5), integrin A5 (ITGA5), integrin B1 (ITGB1), CD44 and ZNF750. Quantitative PCR was used to examine effects on mRNA levels of platelet derived growth factor (PDGFB) and tumor vascular marker CD105. Resveratrol down-regulated angiogenin, VEGF, RGS5, CD105, and the cell adhesion molecules ITGA5, ITGB1 and CD44 in CAL-27 cells. Conversely, it up-regulated ZNF750, PHD2 and PDGFB. These changes were associated with reduced proliferation, reduced colony formation and increased apoptosis. ZNF750 silencing partly reversed these effects of resveratrol. The ability of resveratrol to suppress progression of oral squamous cell carcinoma may involve activation of the ZNF750 pathway and modification of the tumor vascular microenvironment.
Economic Restrictions and Currency Performance: Evidence of African Countries
Authors: Adegboye Alex , Ikpefan Ochei , Oyegoke Adebusola , OJEKA Stephen , Adeyanju Ibukunoluwa
Published: March 2021

This study explores the impact of diverse economic restrictions on currency performance. We assess a panel dataset of 30 African countries for the period 1990–2010. Our empirical evidence is based on the fixed effect regression and the Quantile regression approach. We find that the United States, European Union, economic and intensity sanctions weaken the real exchange rates. However, we establish that the U.N. sanctions are insignificant. As for the policy implication, sanctioned countries should implement a policy that could mitigate the adverse consequences of economic restrictions on currency performance.
Loneliness in Young Adulthood: a Protocol for a Scoping Review of the Quantitative and Qualitative Literature.
Authors: Kirwan Emma , Ó’Súilleabháin Páraic S , Burns Annette , McMahon Jennifer , Summerville Sarah , Creaven Ann-Marie
Published: March 2021

BackgroundLoneliness refers to the distressing feeling that accompanies the experience of perceiving the quantity or quality of one’s social relationships as inadequate (1). There is increasing recognition of the prevalence of loneliness in young adults. Despite this, there is no existing scoping review on loneliness in young adulthood. Young adults (18-25 years) are in a critical life stage involving diverse social, demographic, biological and cognitive transitions which may affect the development of loneliness. Evidence that loneliness is a risk factor for poorer mental and physical health further emphasises the need to understand the experience in this age group. Therefore, the aim of our scoping review is to provide a summary of the quantitative and qualitative literature on loneliness in young adulthood. MethodsThe proposed scoping review will follow the Joanna Briggs Institute methodology and Arksey and O’Malley’s (2005) framework for scoping reviews. Peer-reviewed journal articles and grey literature in the form of reports or difficult-to-locate studies will be identified by: (a) electronic database searching, (b) contacting national and international researchers in the field, and (c) by posting general requests for relevant information on Twitter. We will include all study designs published in English from 2000 to 2021 where loneliness (defined as subjective) is a key focus of the work and the mean age of participants is ≥ 18 and ≤ 25 years. Editorials, commentaries, opinion pieces, dissertations, and book chapters will be excluded. Articles will be selected for inclusion following screening of titles/abstracts succeeded by full-text screening. Results will be presented in a narrative form to provide a descriptive summary of the literature on loneliness in young adults.DiscussionThe results of this scoping review will provide an up-to-date overview of available research related to loneliness in young adults and will inform our future research in the area. Results will be shared through a peer-reviewed journal publication and conference presentations. RegistrationThis protocol is registered with the Open Science Framework (OSF) available at: https://osf.io/jfcmp.
Periplasmic Synthesis and Purification of the Human Prolactin Antagonist Δ1-11-G129R-hPRL
Authors: Suzuki Miriam Fussae , Almeida Larissa Andrade , Pomin Stephanie Angelo , Silva Felipe Douglas , Freire Renan Passos , Oliveira João Ezequiel , Affonso Regina , Soares Carlos Roberto Jorge , Bartolini Paolo
Published: March 2021

The human prolactin antagonist Δ1-11-G129R-hPRL is a 21.9 kDa recombinant protein with 188 amino acids that downregulates the proliferation of a variety of cells expressing prolactin receptors. Periplasmic expression of recombinant proteins in E. coli has been considered an option for obtaining a soluble and correctly folded protein, as an alternative to cytoplasmic production. The aim of this work was, therefore, to synthesize for the first time, the Δ1-11-G129R-hPRL antagonist, testing different activation temperatures and purifying it by classical chromatographic techniques. E. coli BL21(DE3) strain was transformed with a plasmid based on the pET25b(+) vector, DsbA signal sequence and the antagonist cDNA sequence. Different doses of IPTG were added, activating under different temperatures, and extracting the periplasmic fluid via osmotic shock. The best conditions were achieved by activating at 35 °C for 5 h using 0.4 mM IPTG, which gave a specific expression of 0.157±0.015 μg/mL/A600 at a final optical density of 3.43±0.13 A600. Purification was carried out by nickel-affinity chromatography followed by size-exclusion chromatography, quantification being performed via high-performance size-exclusion chromatography (HPSEC). The prolactin antagonist was characterized by SDS-PAGE, Western blotting, reversed-phase high-performance liquid chromatography (RP-HPLC) and MALDI-TOF-MS. The final product presented >95% purity and its antagonistic effects were evaluated in vitro in view of potential clinical applications, including inhibition of the proliferation of cancer cells overexpressing the prolactin receptor and specific antidiabetic properties, taking also advantage of the fact that this antagonist was obtained in a soluble and correctly folded form and without an initial methionine.
On Pickles: Biological and Sociocultural Links Between Fermented Foods and the Human Gut Microbiome
Authors: Flachs Andrew , Orkin Joseph
Published: March 2021

BackgroundThe composition of the human microbiome varies considerably in diversity and density across communities as a function of the foods we eat and the places we live. While all foods contain microbes, humans directly shape this microbial ecology through fermentation. Fermented foods are produced from microbial reactions that depend on local environmental conditions, fermentation practices, and the manner in which foods are prepared and consumed. These interactions are of special interest to ethnobiologists because they link investigations of how people shape and know the world around them to local knowledge, food traditions, local flora, and microbial taxa. MethodsIn this manuscript, we report on data collected at a fermentation revivalist workshop in Tennessee. To ask how fermentation traditions are learned and influence macro and micro ecologies, we conducted interviews and participated in a four-day craft fermentation workshop, and then collected both fermented food products and stool samples from workshop participants eating those fermented foods. ResultsWe identified ten major themes comprised of 29 sub-themes drawn from 326 marked codes in the transcripts. In combination, this analysis allowed us to summarize key experiences with fermentation, particularly those related to a sense of authenticity, place, health, and the discovery of tactile work. From the 605 ASVs shared between food and fecal samples, we identified 25 candidate ASVs that are suspected to have been transmitted from fermented food samples to the gut microbiomes of the workshop participants. Our results indicate that many of the foods prepared and consumed during the workshop were rich sources of probiotic microbes. ConclusionsBy combining these qualitative social and quantitative microbiological data, we suggest that variation in culturally-informed fermentation practices introduces variation in bacterial flora even among very similar foods, and that these food products can influence gut microbial ecology.
Exploring the impact of complex diseases on non-diseased human tissue transcriptomes
Authors: Poon Chi-Lam , Chen Cho-Yi
Published: March 2021

Background

The development of complex diseases is contributed by the combination of multiple factors and complicated interactions between them. Inflammation has recently been associated with many complex diseases and may cause long-term damage to the human body. In this study, we examined whether two types of complex disease systematically altered the transcriptomes of non-diseased human tissues and whether inflammation was linked to identifiable molecular signatures, using post-mortem samples from the Genotype-Tissue Expression (GTEx) project.
Results

Following a series of differential expression (DE) analyses, dozens to hundreds of DE genes were identified in multiple tissues between subjects with and without a history of cerebrovascular disease (CVD) or major depression (MD). DE genes from these disease-associated tissues—the visceral adipose, tibial artery, caudate, and spinal cord for CVD; and the hypothalamus, putamen, and spinal cord for MD—were further analyzed for functional enrichment. Many pathways associated with immunological events were positively enriched in the DEGs of the CVD-associated tissues, as were the neurological and metabolic pathways in the MD-associated tissues. Eight gene–tissue pairs were found to overlap with those prioritized by our transcriptome-wide association studies (TWAS), indicating a potential genetic effect on gene expression for circulating cytokine phenotypes.
Conclusions

Complex diseases like CVD and MD may cause observable changes in the gene expression of non-diseased tissues, suggesting that a long-term impact of diseases, lifestyles and environmental factors may together contribute to the appearance of transcriptomic “scars” on the human body. Furthermore, inflammation is probably one of the systemic and long-lasting effects of cerebrovascular events.
Corilagin Reduces Resistance to PARP Inhibitors by Inhibiting the ERK Signaling Pathway in Ovarian Cancers
Authors: Luan Baoxin , Zhao Hongbo , Bast Robert C. , Lu Zhen , Yu Yinhua
Published: March 2021

Background: Corilagin is a compound with hepatoprotective and antiviral activity extracted from Phyllanthus niruri L. Our previous work demonstrated that corilagin inhibits the growth of ovarian cancer cells by regulating the TGF-β/AKT/ERK signaling. Corilagin was also found to sensitize ovarian cancer cells to paclitaxel and carboplatin by inhibiting the Snail-glycolysis pathway. We have now studied whether corilagin could overcome resistance of ovarian cancer cells to poly ADP ribose polymerase inhibitors (PARPi). PARPi block DNA base excision repair and have been approved for treatment of ovarian cancers. Drug resistance has limited efficacy of PARPi. Methods: We have assessed the effect of corilagin alone and in combination with PARPi in two pairs of ovarian cancer cell lines-A2780CP/A2780CP_R and UWB1.289/UWB1.289_R-that are sensitive or resistant to PARPi. CulcuSyn software (BIOSOFT-Software for Science, Cambridge, U.K.) was used to calculate synergy between two drug combinations. Results: Corilagin was active against all four cell lines and enhanced BMN673 activity synergistically in both PARPi resistant cell lines. PARPi-BMN673 down-regulated the expression levels of PARP and up-regulated pH2AX, it decreased pERK activity in sensitive cell lines, but not in resistant cell lines. While corilagin affected DNA repair function to some extent, it inhibited pERK activity in both PARPi sensitive and resistant cells in a dose dependent manner. Corilagin, but not the BMN673, inhibited ZEB1 in resistant cells. Conclusions: Corilagin deserves further evaluation as a drug that could enhance the activity of PARPi in PARPi-resistant ovarian cancer cells.
Characterization of a haplotype- reference panel for genotyping by low-pass sequencing in Swiss Large White pigs
Authors: Nosková Adéla , Bhati Meenu , Kadri Naveen Kumar , Crysnanto Danang , Neuenschwander Stefan , Hofer Andreas , Pausch Hubert
Published: March 2021

Background
The key-ancestor approach has been frequently applied to prioritize individuals for whole-genome sequencing based on their marginal genetic contribution to current populations. Using this approach, we selected 70 key ancestors from two lines of the Swiss Large White breed that have been selected divergently for fertility and fattening traits and sequenced their genomes with short paired-end reads.
Results
Using pedigree records, we estimated the effective population size of the dam and sire line to 72 and 44, respectively. In order to assess sequence variation in both lines, we sequenced the genomes of 70 boars at an average coverage of 16.69-fold. The boars explained 87.95 and 95.35% of the genetic diversity of the breeding populations of the dam and sire line, respectively. Reference-guided variant discovery using the GATK revealed 26,862,369 polymorphic sites. Principal component, admixture and FST analyses indicated considerable genetic differentiation between the lines. Genomic inbreeding quantified using runs of homozygosity was higher in the sire than dam line (0.28 vs 0.26). Using two complementary approaches (CLR and iHS), we detected 51 signatures of selection. However, only six signatures of selection overlapped between both lines. We used the sequenced haplotypes of the 70 key ancestors as a reference panel to call 22,618,811 genotypes in 175 pigs that had been sequenced at very low coverage (1.11-fold) using GLIMPSE. The genotype concordance, non-reference sensitivity and non-reference discrepancy between thus inferred and Illumina PorcineSNP60 BeadChip-called genotypes was 97.60, 98.73 and 3.24%, respectively. The low-pass sequencing-derived genomic relationship coefficients were highly correlated (r > 0.99) with those obtained from microarray genotyping.
Conclusions
We assessed genetic diversity within and between two lines of the Swiss Large White pig breed. Our analyses revealed considerable differentiation, even though the split into two populations occurred only few generations ago. The sequenced haplotypes of the key ancestor animals enabled us to implement genotyping by low-pass sequencing which offers an intriguing cost-effective approach to increase the variant density over current array-based genotyping by more than 350-fold.