bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering central pathways for industrial-level (3R)-acetoin biosynthesis in Corynebacterium glutamicum
Authors: Lu Lingxue , Mao Yufeng , Kou Mengyun , Cui Zhenzhen , Jin Biao , Chang Zhishuai , Wang Zhiwen , Ma Hongwu , Chen Tao 
Published: April 2020

Abstract
Background: Acetoin, especially the optically pure (3S)- or (3R)-enantiomer, is a high-value-added bio-based platform chemical and important potential pharmaceutical intermediate. Over the past decades, intense efforts have been devoted to the production of acetoin through green biotechniques. However, efficient and economical methods for the production of optically pure acetoin enantiomers are rarely reported. Previously, we systematically engineered the GRAS microorganism Corynebacterium glutamicum to efficiently produce (3R)-acetoin from glucose. Nevertheless, its yield and average productivity were still unsatisfactory for industrial bioprocesses.Results: In this study, cellular carbon fluxes in the acetoin producer CGR6 were further redirected toward acetoin synthesis using several metabolic engineering strategies, including blocking anaplerotic pathways, attenuating key genes of the TCA cycle and integrating additional copies of the alsSD operon into the genome. Among them, the combination of attenuation of citrate synthase and inactivation of phosphoenolpyruvate carboxylase showed a significant synergistic effect on acetoin production. Finally, the optimal engineered strain CGS11 produced a titer of 102.45 g/L acetoin with a yield of 0.419 g/g glucose at a rate of 1.86 g/L/h in a 5 L fermenter. The optical purity of the resulting (3R)-acetoin surpassed 95%.Conclusion: To the best of our knowledge, this is the highest titer of highly enantiomerically enriched (3R)-acetoin, together with a competitive product yield and productivity, achieved in a simple, green processes without expensive additives or substrates. This process therefore opens the possibility to achieve easy, efficient, economical and environmentally-friendly production of (3R)-acetoin via microbial fermentation in the near future.
A common variant of the NOTCH4 gene modulates functional connectivity of the occipital cortex and its relationship with schizotypal traits
Authors: xie xiaohui , Zu Meidan , Zhang Long , Bai Tongjian , Wei Ling , Huang Wanling , JI Gong-Jun , Qiu Bensheng , Hu Panpan , Tian Yanghua , Wang Kai 
Published: April 2020

Abstract
Background: Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. Methods: In present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image（rs-fMRI）. The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). Results: Our results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype.Conclusion: Our results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate.
Dynamic alterations of genome and transcriptome in KRAS G13D mutant CRC PDX model treated with cetuximab.
Authors: zhang hangyu , yuan liyun , liu lulu , yan cong , cheng jinming , fu qihan , tong zhou , jiang weiqin , zheng yi , zhao peng , zhang guoqing , fang weijia 
Published: April 2020

Abstract
Background: KRAS mutations have been characterized as the major predictive biomarkers for resistance to cetuximab treatment. However, studies indicate that not all KRAS mutations are associated with equivalent treatment outcomes. KRAS G13D mutations were observed to account for approximately 16% of all KRAS mutations in advanced colorectal cancer patients, and whether these patients can benefit from cetuximab has not been determined.Methods: An established KRAS G13D mutant colorectal cancer (CRC) patient-derived xenograft (PDX) model was treated with cetuximab. After repeated use of cetuximab, treatment-resistant PDX models were established. Tissue samples were collected before and during treatment, and multiomics data were subsequently sequenced and processed, including whole-exome, mRNA and miRNA data, to explore potential dynamic changes.Results: Cetuximab treatment initially slowed tumor growth, but resistance developed not long after treatment. WES (whole-exome sequencing) and RNA sequencing found that 145 genes had low P values (< 0.01) when analyzed between the locus genotype and its related gene expression level. Among these genes, SWAP70 was believed to be a probable cause of acquired resistance. JAK2, PRKAA1, FGFR2 and RALBP1, as well as 10 filtered immune-related genes, also exhibited dynamic changes during the treatment.Conclusions: Cetuximab may be effective in KRAS G13D mutation patients. Dynamic changes in transcription, as determined by WES and RNA sequencing, occurred after repeated drug exposure, and these changes were believed to be the most likely cause of drug resistance.
A Geriatric Core Curriculum for Undergraduate Dental Students
Authors: Stuck Anna K. , Schimmel Martin 
Published: April 2020

Abstract
BackgroundIt is well-accepted that graduating dentists require geriatric competencies to ensure proper treatment of their elderly patients. Nevertheless, geriatric competencies in a curriculum for undergraduate dental students are often not adequately addressed. Thus, the purpose is to develop an efficient teaching model covering geriatric competencies in a dedicated geriatric core curriculum instructed by a geriatrician.MethodsTo design and develop a geriatric core curriculum, we selected domains based on clinical relevance for dental practice and specified learning objectives, aligning them to discrete competency levels. We used a case-based approach and developed real patient and/or clinical practice scenarios to elaborate the geriatric domains. In a pilot study, we implemented this geriatric core curriculum. Student satisfaction was evaluated using a feedback survey.ResultsOur geriatric core curriculum was successfully implemented for undergraduate dental students in this pilot study. Detailed learning objectives for each domain aligned to corresponding competency levels are described. Clinical practice scenarios for the case-based approach are matched to corresponding domains. Overall, the majority of students rated the domains of polypharmacy (93%), pain (71%), and decision-making capacity (57%) as highly relevant for their future clinical practice. Nevertheless, we encountered several challenges in this pilot study, namely low attendance and a suboptimal learning setting.ConclusionWe conclude that this pilot geriatric core curriculum proves to be largely feasible and serves as an educational template.
Inhibition of autophagy enhanced chemosensitivity in cisplatin resistant hypopharyngeal squamous carcinoma cells
Authors: dong pin , Zhang Jia , Mao Wei , Liu Yuying , Ding Jian , Wang Jie , Yu Ziwei , Huang Ruo fei , Yang Sen , Sun Ying 
Published: April 2020

Abstract
Background: Hypopharyngeal carcinoma is characterized by high degree of malignancy. The most common pathological type is squamous cell carcinoma (HSCC). It has been confirmed that high autophagy level promotes the development of hypopharyngeal cancer in recent years. Clinical researches have reported that high autophagy level often caused insensitivity to chemotherapy, a common phenomenon that greatly reduces therapeutic effect in cisplatin-resistant tumor cell lines. Therefore, exploring internal mechanisms of autophagy on cisplatin resistant HSCC is necessary for founding theoretical basis for synergistic antitumor drugs by interfering with autophagy.Methods: Part I: Cisplatin-resistant FaDu cell line was established and cultured. Cell counting kit-8 was used to detect drug resistance. Inverted microscope was used to observe the morphological changes at different concentrations, then the survival rate was calculated. After MDC staining, the autophagic vacuoles were observed by fluorescence microscopy. The expression of Beclin1 from each group was confirmed by RT-PCR and Western blot method. Part II: Beclin1 was knocked down by plasmid transfection, autophagy inhibitor 3-MA was applied for cisplatin-resistant cells intervention. Cell cycle was detected using flow cytometry assay, apoptosis with necrosis was detected by staining with propidium iodide (PI). CCK-8 was used to observe the cell survival rate in each group. The expression of autophagy-related gene Beclin1,LC3I,LC3II,Atg-5 and P62 in each group was verified by Western blot analysis.Results: Cisplatin-resistant FaDu cell line can be stably constructed by cisplatin intervention. Compared with normal group, autophagy and its related protein Beclin1 expression was enhanced in cisplatin resistant FaDu cells. Autophagy inhibition group showed significant cell cycle changes, mainly manifested by G1 arrest, increased apoptosis rate and significantly decreased survival rate at 24h level. Furthermore, Western blot showed that expression of Beclin1, lc3i, lc3ii, atg-5 protein decreased significantly after the inhibitor used, while the expression of p62 up-regulated, which also confirmed autophagy flow was blocked.Conclusion: Our work confirmed high autophagy level is important for the cisplatin-resistance of HSCC and insensitivity to chemotherapy. The use of 3-MA and Beclin 1 inhibition can significantly reduce autophagy level of cisplatin-resistant FaDu cells, arresting its cell cycle, promote apoptosis and reverse the multidrug resistance condition. These results provide the experimental basis for overcoming multidrug resistance through combination chemotherapy.#These authors contributed equally to this work.
Influence of automated visual field testing on intraocular pressure
Authors: Bertaud Samuel , Borowski Elisabeth Skarbek , Abbas Rachid , Baudouin Christophe , Labbé Antoine 
Published: April 2020

Abstract
Background
To evaluate the influence of automated visual field (VF) testing on intraocular pressure (IOP) in patients with ocular hypertension (OHT) or glaucoma.
Methods
We conducted a prospective observational study from October 2015 to July 2016 at Quinze-Vingts National Ophthalmology Hospital in Paris. Ninety-five right eyes of 95 patients followed for glaucoma or OHT with reliable standard automated perimetry (SAP) were included. IOP was measured three times using a Nidek NT-510 non-contact tonometer within a maximum of 5 minutes before and after VF testing. Subanalyses using logistic regression analysis were performed to evaluate the impact of gender, age, central corneal thickness (CCT), mean deviation (MD) of the VF, VF test duration and filtration surgery on IOP fluctuations.
Results
There was no significant change in IOP after VF testing, with IOP’s 15.14 ± 4.00 mmHg before and 14.98 ± 3.33 mmHg after the VF (P = 0.4). The average change in IOP was 0.15 ± 1.82 mmHg. Using multivariate analysis, no effect of the VF test on IOP was found (global model fit R²=0.12), whether based on duration of the VF test (P = 0.18) or the MD (P = 0.7) after adjustment for age, gender, CCT and history of glaucoma surgery. Similarly, there was no significant difference within different types of glaucoma, including open-angle glaucoma (p = 0.36), chronic angle closure glaucoma (P = 0.85) and OHT (P = 0.42). The subgroup of patients with an IOP elevation > 2 mmHg had a significantly higher SAP test duration (P = 0.002).
Conclusion
VF testing by SAP does not influence IOP as measured with a non-contact tonometer.
Antibiotics Prescription for Febrile Outpatients: A Health Facility-Based Secondary Data Analysis for the Greater Accra region of Ghana
Authors: Opoku Michael Mireku , Bonful Harriet Affran , Koram Kwadwo A. 
Published: April 2020

Abstract
Background Misguided prescription of antibiotics is an important facilitator of the emergence and spread of antibiotic resistance. In the absence of the implementation of effective interventions to control antibiotic use, its consumption may increase out of proportion to requirements. Antibiotic stewardship interventions must be appropriately targeted and assessed to enhance the proper use of antibiotics. The objective of this study was to determine the factors associated with antibiotics prescription to febrile outpatients who seek care in health facilities within the Greater Accra region of Ghana.Methods Secondary data obtained from a review of medical records of 2,519 febrile patients at the outpatient department of 6 health facilities in 3 municipalities during the baseline survey of a quasi-experiment in 2016 were used. The primary outcome was prescription of any antibiotic. Independent variables included patients’ demographics, symptoms, laboratory investigations (blood film microscopy, malaria rapid diagnostic test, full blood count, urine and stool routine examinations), diagnoses, and prescribers’ demographics. Crude and adjusted logistic regression analyses were used to determine the factors associated with antibiotics prescription.Results The prevalence of antibiotics prescription was 70.1% (95% CI: 67.7–72.4). Prescribers with more years of practice (> 5 years) were more likely to prescribe antibiotics compared to those with less than 3 years of practice (p < 0.001). Integrated Management of Neonatal and Childhood Illnesses (IMNCI) training was associated with a 2.3 (95% CI: 1.54, 3.53, p < 0.001) times higher odds of antibiotic prescribing. Patients aged 5 years or more were 60% less likely to be prescribed antibiotics compared with those under 5 years (AOR = 0.40, 95% CI: 0.32, 0.51; p < 0.001). Patients referred for laboratory investigations were 29% less likely to be prescribed with antibiotics than those not referred. Presenting to the outpatient clinic with cough was associated with a 3.5 (95% CI: 2.54, 4.92) times higher odds of antibiotics prescribing.Conclusion Prescription of antibiotics to febrile outpatients was high. Promoting laboratory testing can potentially reduce irrational antibiotics prescribing. Prescribing antibiotics for children under five and the prescribing practices of prescribers with longer years of practice should be targeted with interventions to reduce high use of antibiotics.
Ileal proteomic changes associated with IL-25-mediated resistance against intestinal trematode infections
Authors: Álvarez-Izquierdo María , Esteban J. Guillermo , Muñoz-Antoli Carla , Toledo Rafael 
Published: April 2020

Abstract
Background: Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been extensively used to investigate the factors that determine the rejection of intestinal helminths. In this sense, several studies have shown that IL-25 is critical for the development of resistance against E. caproni in mice. In fact, treatment of mice with recombinant IL-25 generates resistance against primary E. caproni infection. However, the mechanisms by which IL-25 induces resistance remain unknown.Methods: To study the mechanisms responsible for resistance elicited by IL-25, we analyze the ileal proteomic changes induced by IL-25 in mice and their potential role in resistance. To this purpose, we compare the protein expression profiles in the ileum of four experimental groups of mice: naïve controls; E. caproni-infected mice; rIL-25-treated mice; and rIL-25-treated mice exposed to E. caproni metacercariae.Results: Quantitative comparison by 2D-DIGE showed significant changes in a total of 41 spots. Forty of those spots validated protein spots were identified by mass spectrometry corresponding to 24 proteins.Conclusions: The analysis of our results indicates that resistance to infectiuon is associated with the maintenance of the intestinal epithelial homeostasis and the regulation of proliferation and cell death. These results provide new insights into the proteins involved in the regulation of tissue homeostasis after intestinal infection and its transcendence in resistance.
NAMPT/SIRT2–mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells
Authors: Xu Yun , Nasri Masoud , Dannenmann Benjamin , Mir Perihan , Zahabi Azadeh , Welte Karl , Morishima Tatsuya , Skokowa Julia 
Published: April 2020

Abstract
Background: Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins (SIRTs). SIRTs regulate functions of histones and none-histone proteins. The role of NAMPT/SIRTs pathway in the regulation of maintenance and differentiation of human induced pluripotent stem (iPS) cells is not fully elucidated. Methods: We evaluated the effects of specific inhibitors of NAMPT-, or SIRT2 on the pluripotency, proliferation, survival and hematopoietic differentiation of human iPS cells. We also studied the molecular mechanism downstream of NAMPT/SIRTs in iPS cells. Results: We demonstrated that NAMPT is indispensable for the maintenance, survival and hematopoietic differentiation of induced pluripotent stem (iPS) cells. We found that inhibition of NAMPT or SIRT2 in iPS cells induces p53 protein by promoting its lysine acetylation. This leads to activation of the p53 target, p21, with subsequent cell cycle arrest and induction of apoptosis in iPS cells. NAMPT and SIRT2 inhibition also affects hematopoietic differentiation of iPS cells in an embryoid body (EB)-based cell culture system. Conclusions: Our data demonstrate the essential role of the NAMPT/SIRT2/p53/p21 signaling axis in the maintenance and hematopoietic differentiation of iPS cells.
Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis
Authors: Gäckler Anja , Schönermarck Ulf , Dobronravov Vladimir , Manna Gaetano La , Denker Andrew , Liu Peng , Vinogradova Maria , Yoon Sung-Soo , Praga Manuel 
Published: April 2020

Abstract
Background: Atypical hemolytic uremic syndrome (aHUS) triggered by pregnancy is a rare disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor obtained through selective modifications to eculizumab, is efficacious in inhibiting complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. In this analysis, we report outcomes in a subgroup of patients from the 311 study who developed TMA postpartum.Methods: This was a phase 3, multicenter trial evaluating efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete TMA response (simultaneous platelet count normalization [≥150 x 109/L], lactate dehydrogenase normalization [≤246 U/L] and 25% improvement in serum creatinine) through the 183-day initial evaluation period. Additional efficacy endpoints included time to complete TMA response, hematologic normalization, and dialysis requirement status. Results: Eight patients presenting with TMA postpartum (median age of 37.7 [range; 22.1–45.2] years) were diagnosed with aHUS and received ≥1 dose of ravulizumab. Five patients (63%) were on dialysis at baseline. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 31.5 days. Hematologic normalization was observed in all patients. All patients on dialysis at baseline discontinued dialysis within 21 days after treatment with ravulizumab. All patients showed continued improvements in the estimated glomerular filtration rate from baseline to Day 183. Three possible treatment-related adverse events were observed in 2 patients (arthralgia and nasopharyngitis [both non-severe]; urinary tract infection). No deaths or meningococcal infections occurred.Conclusions: Treatment with ravulizumab provided immediate and complete C5 inhibition, resulting in rapid clinical and laboratory improvements and complete TMA response through 183 days in patients with aHUS triggered by pregnancy. The safety profile observed in this subset of patients analysed is consistent with the 311 study investigating ravulizumab in patients with aHUS naïve to complement treatment. Clinical trial identifier: NCT02949128
Comparison of Body Mass Index (BMI) and fat percentage criteria classification of 7-13 year old rural boys in the Eastern Cape, South Africa
Authors: Gent Maya van , Pienaar Anita , Noorbhai Habib 
Published: April 2020

Abstract
Background:

The aim of this paper is to investigate whether BMI and fat percentage classification criteria, would classify a sample in similar criteria’s.
Methods:

A cross-sectional study with a stratified random sampling included 602 rural boys (7–13 years old). Fat percentage criteria classification and BMI was measured Maturity, age and peak height velocity (PHV) were indirectly determined. Statistical techniques included descriptive, Pearson product correlation, the Kappa agreement test and the McNemar’s test. The level of statistical significance was set at p ≤ 0.05.
Results:

All age groups presented statistically significant high correlations between BMI and fat percentage, and low to medium correlations between fat percentage and maturity age (MA). Measurement of agreement between BMI and fat percentage classifications showed poor to fair agreements for all age groups, with the exception of the eight-year old group which presented a moderate agreement.
Conclusion:

Classifications according to BMI and fat percentage, results in different classifications for the same population. Classifications for categorizing purpose should make use of adiposity rather than BMI, as it includes fat free mass within the assessment protocol.
A New View into the Silica Deposition Vesicles of Diatoms
Authors: Heintze Christoph , Formanek Petr , Pohl Darius , Hauptstein Jannes , Rellinghaus Bernd , Kröger Nils 
Published: April 2020

Abstract
Diatoms are single-celled microalgae that produce silica-based cell walls with intricate nano- and micropatterns. Biogenesis of diatom biosilica is a bottom-up process that occurs in large intracellular compartments termed silica deposition vesicles (SDVs). Investigating the mechanism of silica morphogenesis has so far been severely limited by the lack of methods for imaging the entire volume of an SDV with high spatial resolution during all stages of development. Here we have developed a method that allows for rapid identification and electron microscopy imaging of many different, full sized SDVs that are in the process of producing biosilica valves. This enabled visualizing the development of characteristic morphological biosilica features with unprecedented spatio-temporal resolution. During early to mid-term development, valve SDVs contained ~ 20 nm sized particles that were primarily associated with the radially expanding rib-like biosilica structures. The results from electron dispersive X-ray analysis suggests that the immature biosilica patterns are silica-organic composites. This supports the hypothesis that silica morphogenesis is dependent on organic biomolecules inside the SDV lumen.