bluuebunny/crossref_metadata_2025 huggingface dataset:
The Memory Effect on Fractional Calculus: An Application in the Spread of Covid-19
Authors: de Barros Laécio Carvalho , Lopes Michele Martins , Simões Francielle Santo Pedro , Esmi Estevão , Santos José Paulo Carvalho dos , Sánchez Daniel Eduardo
Published: July 2020

Fractional calculus has been widely used in mathematical modeling of evolutionary systems with memory effect on dynamics. The main interest of this work is, through a statistical approach, to attest how the hysteresis phenomenon, which describes the memory effect present in biological systems, can be treated by fractional calculus, and to analyze the contribution of the historical values of a function in the evaluation of fractional operators according their order. In order to illustrate the efficiency of this non-integer order calculus, we consider the SIR (Susceptible-Infected-Recovered) compartmental model which is widely used in epidemiology. We employ SIR models to model the dynamics, with and without memory, of the spread of Covid-19 in some countries.
A false alarm of COVID-19 pneumonia in lung cancer: a case report of anti-PD-1 related pneumonitis and literature review
Authors: Dai Ying , Dai Ying , Liu Sha , Liu Sha , Zhao Zhiyan , Zhao Zhiyan , Li Xiaqiu , Li Xiaqiu , Zhang Yiruo , Zhang Yiruo , Liu Pingping , Liu Pingping , Du Yingying , Du Yingying
Published: July 2020

Background: The fatal toxicity of anti-PD-1/PD-L1 agents is pneumonitis. The diagnosis consists of the history of immunotherapy, clinical symptoms and presentation of computed tomography (CT) imaging. The typical CT findings include ground-glass opacities. Based on the similar radiographic feature with 2019 Novel Coronavirus (COVID-19) pneumonia, clinicians are cautious to evaluate diagnosis especially in COVID-19 epidemic areas. Case presentation: Herein we report a 67-year-old male patient with advanced non-small cell lung cancer developed pneumonitis post Sintilimab injection. The dyspnea appeared at the 15th day of close contact with his son who returned from Wuhan, but not accompanied with fever. The chest CT indicated peripherally subpleural lattice opacities at the inferior right lung lobe and bilateral thoracic infusion. The real-time reverse-transcription polymerase-chain-reaction (RT-PCR) from double swab samples within 72 hours remained negative. The patient was thereafter treated with prednisolone and antibiotics for over two weeks. Thereafter the chest CT demonstrated the former lesion almost absorbed, in line with prominently falling CRP level. The anti-PD-1 related pneumonitis with bacterial infection was diagnosed finally based on the clinical evidence and good response to the prednisolone and antibiotics. Conclusion: Both ani-PD-1 related pneumonitis and COVID-19 pneumonia harbor the common clinical symptom and the varied features of CT imaging. Differential diagnosis was based on the epidemiological and immunotherapy histories, RT-PCR tests. The response to glucocorticoid can indirectly help the diagnosis.
Impact of Insulin Initiation and Time to Insulin Initiation on within-Person Change of Healthcare Utilization in Medicaid Enrollees with type 2 Diabetes
Authors: Xue Lingshu , Strotmeyer Elsa S. , Zgibor Janice , Costacou Tina , Boudreau Robert , Kelley David , Donohue Julie M.
Published: July 2020

Background: Insulin use, time to insulin initiation, and subsequent healthcare utilization in low-income adults with type 2 diabetes (T2DM) are poorly understood.Methods: Our objectives were to examine whether 1) insulin initiation and 2) every 1-year decrease in the time from first-line glucose-lowering agents (GLAs) to insulin initiation reduced healthcare utilization within 12 months after insulin initiation in Pennsylvania (PA) Medicaid enrollees with T2DM. We included a cohort of 12,648 PA Medicaid enrollees (age 47.3±10.3 years) with first-line non-insulin GLAs between 2008 and 2016. Insulin users (N=3,625) were matched with non-insulin users (N=9,023) on dates of 1st GLA prescription and propensity scores calculated based on baseline characteristics to account for potential confounders. Generalized estimating equations models estimated within-person changes in inpatient stays and emergency room (ER) visits 12 months after vs. 12 months before insulin initiation. We performed sensitivity analyses in young (18-45 years) and middle-aged enrollees (>45 to 64 years). Results: The average time from first-line GLAs to insulin initiation was 2.0±1.7 years. Neither insulin initiation (rate ratio [RR]:1.0 [1.0, 1.1]) nor time to insulin initiation (RR: 1.0 [1.0, 1.0]) was associated with within-person change in ER visits. In young T2DM adults, insulin users had a greater subsequent increase in inpatient stays after insulin initiation vs. non-insulin users over the same time period (RR: 1.3 [1.1, 1.5]). Conclusions: In T2DM Medicaid enrollees, no reduction in healthcare utilization was observed after insulin initiation, even in early stages of pharmacotherapy. Studies investigating primary contributors to the increased inpatient use in young insulin users with T2DM are needed.
The Experiences of Individuals With Cervical Spinal Cord Injury and Their Family During Post-injury Care in Non-Specialised and Specialised Units in UK
Authors: McRae Jackie , Smith Christina , Emmanuel Anton , Beeke Suzanne
Published: July 2020

BackgroundIndividuals with acute cervical spinal cord injury require specialised interventions to ensure optimal clinical outcomes especially for respiratory, swallowing and communication impairments. This study explores the experiences of post-injury care for individuals with cervical spinal cord injury and their family members during admissions in specialised and non-specialised units in the United Kingdom.MethodsSemi-structured interviews were undertaken with individuals with a cervical spinal cord injury and their family member, focussing on the experience of care across units. Eight people with spinal cord injury levels from C2 to C6, were interviewed in their current care settings. Six participants had family members present to support them. Interviews were audio-recorded and transcribed with data inputted into NVivo for thematic analysis.Results The study identified six themes from the participant interviews that highlighted different experiences of care in non-specialised and specialised settings. A number of these were related to challenges with the system, whilst others were about the personal journey of recovery. The themes were titled as: adjustment, transitions, “the golden opportunity”, “when you can’t eat”, communication, and “in the hands of the nurses and doctors”.ConclusionsWhilst participants reported being well cared for in non-specialised units, they felt that they did not receive specialist care and this delayed their rehabilitation. Participants were dependent on healthcare professionals for information and care and at times lost hope for recovery. Staff in non-specialised units require training and guidance to help provide support for those with dysphagia and communication difficulties, as well as reassurance to patients and families whilst they wait for transfer to specialised units.
Tubeless Uniportal Thoracoscopic Wedge Resection with Modified Air Leak Test and Chest Tube Drainage
Authors: Liu Zhengcheng , Yang Rusong , Sun Yang
Published: July 2020

Background: To investigate whether tubeless uniportal thoracoscopic wedge resection has better short-term outcomes than non-intubated approach with chest tube drainage.Methods: Data were collected retrospectively from January 2017 and December 2019. Tubeless group included 55 patients with pulmonary nodules underwent tubeless uniportal thoracoscopic wedge resection, 211 patients underwent non-intubated uniportal thoracoscopic wedge resection with chest tube drainage were included in drainage group. Perioperative outcomes between two groups were compared. Results: After 1:1 matching, 110 patients remained for analysis, baseline demographic and clinical variables were comparable between the two groups. Mean incision size was 3 cm in both group. Mean operative time was 59.3 minutes in tubeless group and 52.8 minutes in drainage group. The detectable mean lowest SpO2 and mean peak EtCO2 during operation was acceptable in both groups. Conversion to intubated ventilation or thoracotomy was not required. No patient failed the air leak test and did not undergo a tubeless procedure. Mean postoperative hospital stay was 1.5 days in tubeless group and 2.5 days in drainage group. Residual pneumothorax or subcutaneous emphysema was not frequent and mild in tubeless group. The postoperative pain VAS score was pain score was significantly lower in tubeless group in post-operative day 1 and 3. Side effects were rare and mild, including cough and hemoptysis. No reintervention or readmission occurred.Conclusions: Tubeless uniportal thoracoscopic wedge resection with modified air leak test and chest tube drainage is feasible and safe for selected patients with peripheral pulmonary nodules, it might reduce post-operation pain and lead to faster recovery.
Surgical Care in Poland after COVID19 Outbreak: A National Survey.
Authors: Stefura Tomasz , Rymarowicz Justyna , Wysocki Michał , Szeliga Jacek , Wallner Grzegorz , Pędziwiatr Michał , Nowakowski Michał , Major Piotr
Published: July 2020

Background: During COVID-19 pandemic, it is necessary to collect and analyze data concerning management of hospitals and wards to work out solutions for potential future crisis. The objective of the study was to investigate how surgical wards in Poland are managing during rapid development of the COVID-19 pandemicMethods: An anonymous, online survey was designed and distributed to surgeons and surgery residents working in surgical departments during pandemic. Responders were divided into two groups: Group 1 (responders working in a “COVID-19-dedicated” hospital) and Group 2 (responders working in other hospitals). Results: Overall, 323 responders were included in the study group, 30.03% of which were female. Medical staff deficits were reported by 21.15% responders from Group 1 and 29.52% responders from Group 2 (p=0.003). The mean number of elective surgeries performed weekly prior to the pandemic in Group 1 was 40.37±46.31 and during the pandemic was 13.98±37.49 (p<0.001). In Group 2, the mean number of elective surgeries performed weekly before the start of the pandemic was 26.85±23.52 and after the start of the pandemic, it was 7.65±13.49 (p<0.001). There were significantly higher reported levels of preparedness in Group 1 in terms of: theoretical training of the staff, equipping the staff and adapting the operating theater to safely perform procedures on patients with COVID-19. Overall, 62.23% of responders presume being infected with SARS-CoV-2.Conclusions: SARS-CoV-2 pandemic had a significantly negative impact on surgical wards. Despite the preparations, the number of responders who presume being infected with SARS-CoV-2 during present crisis is high.Trial registration: The study was registered in https://www.clinicaltrials.gov/ registry (NCT04368026).
Insulin receptor activation by proinsulin preserves synapses and vision in retinitis pigmentosa
Authors: Sánchez-Cruz Alonso , Hernández-Pinto Alberto , Lillo Concepción , Isiegas Carolina , Marchena Miguel , Lizasoain Ignacio , Bosch Fátima , Villa Pedro de la , Hernández-Sánchez Catalina , Rosa Enrique J. de la
Published: July 2020

Background Synaptic loss, neuronal cell death, and circuit remodeling are common features of central nervous system neurodegenerative disorders. Retinitis pigmentosa, the leading cause of inherited blindness, is a group of retinal dystrophies characterized by photoreceptor cell dysfunction and death. The insulin receptor, a key controller of metabolism, also regulates neuronal survival and synaptic formation, maintenance, and activity. Indeed, deficient insulin receptor signaling has been implicated in several brain neurodegenerative pathologies. Methods We employed a gene therapy strategy to enhance insulin receptor signaling in the Pde6b rd10/rd10 mouse model of RP by using recombinant AAV serotype 2/1 viral vectors bearing cDNA from the human proinsulin gene. Insulin receptor expression and signaling were analyzed by PCR and immunostaining. Synaptic connectivity was evaluated by electron microscopy and immunostaining. Proinsulin levels were measured by ELISA. Photoreceptor preservation was assayed by histological analysis and visual function was assessed by electroretinography and optomotor test. Results We present evidence linking impaired insulin receptor signaling with retinitis pigmentosa. We found a selective decrease in the levels of the insulin receptor and its downstream effector phospho-S6 in retinal horizontal cell axons in the rd10 mouse model of retinitis pigmentosa, as well as aberrant synapses between rod photoreceptors and the postsynaptic terminals of horizontal and bipolar cells. A gene therapy strategy to induce sustained proinsulin production restored retinal insulin receptor signaling, by increasing S6 phosphorylation, without peripheral metabolic consequences. Moreover, proinsulin preserved photoreceptor synaptic connectivity and prolonged visual function as determined by electroretinography and optomotor tests. Conclusion These findings point to a disease-modifying role of insulin receptor and support the therapeutic potential of proinsulin in retinitis pigmentosa.
Staphylococcus Aureus: Selective Reporting of Antibiogram Results and Its Impact on Antibiotic Use. Interventional Study with a Reference Group on the Effect of Switching from Non-Selective to Selective Antibiotic Reporting
Authors: Lestin-Bernstein Franka , Harberg Ramona , Schumacher Ingo , Briedigkeit Lutz , Heese Oliver , Biedermann Kristina
Published: July 2020

Background:Antimicrobial stewardship (AMS) strategies worldwide focus on optimised antibiotic use. Selective susceptibility reporting is recommended as an effective AMS tool, although there is a lack of representative studies investigating the impact of selective susceptibility reporting on antibiotic use.The aim of this study was to investigate the impact of selective susceptibility reporting of Staphylococcus aureus (S. aureus) on antibiotic consumption. Enhancing the use of narrow-spectrum beta-lactam antibiotics such as flucloxacillin/cefazolin/cefalexin is one of the main goals in optimising antibiotic therapy of S. aureus infections.Methods:This interventional study with control group was conducted at a tertiary care hospital in Germany. During the one-year interventional period, susceptibility reports for all methicillin-sensitive S. aureus (MSSA) were restricted to flucloxacillin/cefazolin/oral cefalexin, trimethoprim-sulfamethoxazole, clindamycin, gentamicin and rifampin/fosfomycin; instead of reporting all tested antibiotics during the year before the intervention and in the reference clinic. The impact of the intervention was analysed by monitoring antibiotic consumption (recommended daily dose/100 occupied bed days: RDD/100 BD).Results:MSSA-antibiograms were reported for 2836 patients. Total use of narrow-spectrum beta-lactams more than doubled during the intervention (from 1.2 to 2.8 RDD/100 BD, P<0.001; P<0.001 compared to the reference clinic); the percentage of total antibiotic use increased from 2.6% to 6.2%. A slight, but significant increase in the use of trimethoprim-sulfamethoxazole was also observed (+ 0.37 RDD/100 BD).There was no decrease in antibiotics withdrawn from the antibiogram, probably as a consequence of their wide use for indications other than S. aureus infections.Conclusions:As narrow-spectrum beta-lactams are not widely used for other infections, there is a strong indication that selective reporting guided clinicians to optimised antibiotic therapy of S. aureus infections.As useful AMS tool, we recommend implementing selective reporting rules into the national/international standards for susceptibility reporting.
Rumen microbiome structure and metabolites activity in dairy cows with clinical and subclinical mastitis
Authors: Wang Yue , Nan xuemei , Zhao Yiguang , Wang Mengling , Wang Hui , Zhang Fan , Xue Fuguang , Hua Dengke , Liu Jun , Jiang Linshu , Yao Junhu , Xiong Benhai
Published: July 2020

Background: With high prevalence and complex etiology, bovine mastitis (BM) often causes serious damage to dairy cows’ health and milk quality. Although the shift in milk has been the main research interest on mastitis, recent studies have suggested that gastrointestinal microorganism has a crucial effect on the inflammation of the tissues outside the gut, such as mammary gland. However, studies related to the variation of rumen inner-environment during mastitis were limited. This study compared the differences of rumen microorganisms and metabolites under different udder health conditions, in order to investigate the correlation between udder health status and rumen microbiome structure and metabolites activity. Based on the somatic cell counts (SCC), California mastitis test (CMT) parameters and clinical symptoms of mastitis, 60 lactating Holstein dairy cows with similar body conditions (excepted for udder health condition) were divided into 3 groups (n = 20 per group): healthy (H) group, subclinical mastitis (SM) group and clinical mastitis (CM) group. Lactation and rumen fermentation parameters were detected, and rumen microbiota and metabolites were analyzed via 16S rRNA amplicon sequencing and untargeted metabolomics, respectively. Results: As the degree of mastitis increased, milk SCC and milk protein were significantly increased (P < 0.01). Milk yield, milk fat and lactose (P < 0.01), and rumen lactic acid (LA) (P < 0.01), acetate, propionate, butyrate, valerate (P < 0.001), total volatile fatty acids (TVFAs) concentrations (P < 0.01) and pH value (P = 0.024) were significantly decreased. In the rumen of CM cows, the significantly increased pathogens related to intestinal and oral inflammation, such as g__Lachnospiraceae_UCG-006 (P = 0.03), g__Moraxella and g__norank_f__Neisseriaceae (P < 0.01), etc., were accompanied by a significant increase in 12-oxo-20-dihydroxy-leukotriene B4 and 10beta-Hydroxy-6beta-isobutyrylfuranoeremophilane (P < 0.01). Meanwhile, in the rumen of SM cows, the g__Ruminiclostridium_9 (P = 0.04) and g_Enterorhabdus (P = 0.01) were increased with methenamine, 5-Hydroxymethyl-2-furancarboxaldehyde (5-HMF) and 6-Methoxymellein (P < 0.01). During mastitis, the decrease of short-chain fatty acids (SCFAs)-producing bacteria and intestinal probiotics in rumen, including g__Prevoterotoella_1 and g__Bifidobacterium (P = 0.03), etc., were significantly reduced, accompanied by a reduction in 2-Phenylbutyric acid (2-PBA) (P < 0.01).Conclusion: This study suggested that the microflora and metabolites associated with pathogen invasion, inflammatory response and rumen wall damage in the rumen of cows suffered mastitis were prominent.
What are the challenges of pedestrian safety from the viewpoints of traffic and transport stakeholders? A qualitative Study
Authors: Haghighi Morteza , Aghdam Fatemeh Bakhtari , Sadeghi-Bazargani Homayoun , Nadrian Haidar
Published: July 2020

Background

Pedestrians are among the most vulnerable groups in traffic accidents. Our aim in this study was to explore the challenges associated to pedestrian safety from the perspective of traffic and transport stakeholders.
Methods

In 2018, applying a qualitative approach, twenty-four traffic and transport stakeholders were invited to participate in semi-structured individual interviews in Tabriz, Iran. To analyze data, conventional content analysis approach was used. MAXQDA software version 11 was applied to manage data analysis process.
Findings:

Participants reported a wide range of challenges which were grouped into six categories: "Challenges related to pedestrians", "Challenges related to drivers", "Management system challenges", "Environmental infrastructure challenges", "Educational and media challenges", and "Challenges of legislation and enforcement".
Conclusion

We identified pedestrian safety as a challenging urban traffic and transport issue with specific complexities, particularly in the management system. With a holistic approach to the challenges, as discussed inside, all reported obstacles seem to be overshadowed by one core challenge, namely the lack of a traffic management system with health-oriented approach and enough authority. Using evidence while policy-making and intervention planning, as well as media support is recommended.
Comparison of CRB/CRB-65, qSOFA, and SIRS for Risk Prediction in Patients with Urinary Tract Infection
Authors: Bae Sung Jin , Lee Jae Hee , Choi Yoon Hee
Published: July 2020

Background: Early recognition of sepsis is critical for improving patient outcomes. In approximately 20%-30% of patients, sepsis resulted from urinary tract infection (UTI). This study aimed to investigate the effectiveness of CRB (confusion, respiratory rate, blood pressure), CRB-65, and quick sequential organ failure assessment (qSOFA) in predicting intensive care unit (ICU) admission and in-hospital mortality of patients with UTI and compare them with Systemic Inflammatory Response Syndrome (SIRS). Methods: This retrospective cohort study included patients with UTI who visited the emergency department of a single medical center between February 2018 and March 2020. Baseline characteristic data were obtained and compared with the prevalence of ICU admission and in-hospital mortality. The effectiveness of CRB, CRB-65, qSOFA, and SIRS as indicators of ICU admission and in-hospital mortality was evaluated using the area under the receiver operating characteristic (AUROC) curve. Results: Overall, 1151 patients were included in this study, of whom 132 (11.5%) were admitted to the ICU and 30 (2.6%) succumbed to in-hospital mortality. AUROC values of CRB, CRB-65, and qSOFA as predictors of ICU admission and in-hospital mortality were similar. The CRB score of ≥1 had a sensitivity and specificity of 71.3% and 73.5%, respectively, for ICU admission and 66.7% and 69.2%, respectively, for in-hospital mortality. The CRB-65 score of ≥2 had a sensitivity and specificity of 61.2% and 80.9%, respectively, for ICU admissions and 60% and 76.9%, respectively, for in-hospital mortality. The qSOFA score of ≥1 had a sensitivity and specificity of 71.3% and 79.6%, respectively, for ICU admission and 66.7% and 74.8%, respectively, for in-hospital mortality. Conclusion: CRB, CRB-65, and qSOFA were more effective predictors than SIRS for patients with UTI. CRB, CRB-65, and qSOFA had similar general values for predicting outcomes in patients with UTI in the emergency department.
Peer Assisted Study Session (PASS): Are the Millennial Leaders the Leaders of Tomorrow? A Prospective Cohort Study.
Authors: Shafiaai Mohd Syameer Firdaus Mohd , Kadirvelu Amudha , Pamidi Narendra
Published: July 2020

Background PASS is a peer-led structured academic mentoring program designed to provide academic assistance for new students in their transition from college to university studies and also for students struggling in certain units. This study aims to establish acquired skills by peer leaders associated with peer-led mentoring via PASS program, and to explore the role played by these acquired skills in their journey to become a successful doctor.Methods Study participants were forty selected second-year undergraduate medical students at Monash University Malaysia with commendable examination results. Validated pre-test and post-test questionnaires were administered to explore changes in the level of communication, leadership, professional, and pedagogical skills before and after participation in peer mentoring program. Qualitative analysis of focused group interviews was performed by an independent investigator to identify how the skills developed as a peer mentor may help with becoming a good doctor. Major themes were identified with the thematic-analysis approach.Results Thirty-eight students completed the pre-test and post-test questionnaires. Peer leaders reported improvement in oral and written skills for teaching; increased confidence to give constructive feedback; better stress management; efficient time management; improved interpersonal skills; and enhanced problem-solving and critical thinking capabilities. Eight major themes were identified from the interview and peer leaders reported positive experience of working in diverse environments and shouldering of responsibilities.Conclusions Peer-led mentoring provides a good opportunity for medical students to shoulder responsibilities as a leader and offers an of experience of managing a team of their peers and juniors which in turn may enhance their communication, interpersonal, and leadership skills.
New insights in the reproducibility of visual and electronic tooth color assessment for dental practice
Authors: Ratzmann Anja , Welk Alexander , Hoppe Stephanie , Fanghaenel Jochen , Schwahn Christian
Published: July 2020

Background The aim of the study was to compare a 2D and 3D color system concerning a variety of statistical and graphical methods to assess validity and reliability of color measurements, and to give some guidance when to use which system and how to interpret color distance measures, including ΔE and d(0M1).Methods The tooth color of teeth 14 to 24 of 35 patients with a regular bleaching treatment (BT) was visually assessed and electronically measured with the spectrophotometer Shade Inspector™. Tooth color was recorded before BT (T1/T2- Baseline), 14d (T3/T4) and 6 months (T5/T6) after BT. VITAPAN® Classical (VC) and VITA-3D-Master® (3D) served as reference systems.Results Intra-rater variability. The 2D system is better than the 3D system both visually and electronically in terms of ΔE and d(0M1) for statistics of agreement and reliability. All four methods show strong patterns of disagreement between repeated measurements in Bland-Altman plots. The 3D system lacks reliability of hue compared with that of lightness and chroma, which is more pronounced visually than electronically. The smallest detectable color difference (SDCD) differs by the four methods used and is most favorable in the electronical 2D system. Inter-rater variability. The agreement between the 2D and 3D system in terms of ΔE is not good according to Byrt’s classification. It is lower within the electronical method than within the visual method. Comparability of the 2D and 3D system is uncertain because confidence intervals of ICCs accounting for systematic error are wide. The systematic error between the 2D and 3D system cannot be neglected. The reliability of the visual and electronical method is substantially the same within the 2D and 3D system; this comparability is fair to good.Clinical Relevance: According to the results of this study, the 3D system may confuse human raters and even electronical devices. The 2D system is the natural and best choice.
MAL62 overexpression enhances uridine diphosphoglucose-dependent trehalose synthesis and glycerol metabolism for cryoprotection of baker’s yeast in lean dough
Authors: Sun Xi , Zhang Jun , Fan Hua Zhi , Xiao Ping , Li Feng , Liu Qing Hai , Zhu Bi Wen
Published: July 2020

Background: In Saccharomyces cerevisiae, the alpha-glucosidase (maltase) is a key enzyme in maltose metabolism. Overexpression of the alpha-glucosidase-encoding gene MAL62 has been shown to increase the freezing tolerance of yeast in lean dough. However, its cryoprotection mechanism is still not clear.Results: RNA sequencing (RNA-seq) revealed that MAL62 overexpression increased transcription of uridine diphosphoglucose (UDPG)-dependent trehalose synthesis. The changes in transcript abundance were confirmed by quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and enzyme activity assays. When the UDPG-dependent trehalose synthase activity was abolished, MAL62 overexpression failed to promote the synthesis of intracellular trehalose. Moreover, in strains lacking trehalose synthesis, cell viability in the late phase of prefermentation freezing coupled with MAL62 overexpression was slightly reduced, which can be explained by the increase in intracellular glycerol concentration which was consistent with the elevated transcription of glycerol synthesis pathways. Conclusions: The increased freezing tolerance by MAL62 overexpression is mainly achieved by the increased trehalose content via the UDPG-dependent pathway, and glycerol plays a secondary role. These findings shed new light to the mechanism of yeast response to freezing in lean bread dough and can help the improvement of industrial yeast strains.
A combination of genome reduction and promoter engineering can enhance surfactin production by Bacillus amyloliquefaciens LL3
Authors: Zhang Fang , Huo Kaiyue , Song Xingyi , Quan Yufen , Gao Weixia , Wang Shufang , Yang Chao
Published: July 2020

Background: Genome reduction and metabolic engineering have emerged as intensive research hotspots for constructing the optimal functional chassis and various microbial cell factories. Surfactin, a lipopeptide-type biosurfactant with broad spectrum antibiotic activity, has wide application prospects in anticancer therapy, biocontrol and bioremediation. Bacillus amyloliquefaciens LL3, previously isolated by our lab, contains an intact srfA operon in the genome for surfactin biosynthesis.Results: In this study, a genome-reduced strain GR167 lacking ~4.18% of the B. amyloliquefaciens LL3 genome was constructed by deleting some unnecessary genomic regions. Compared with the strain NK-1 (LL3 derivative, ΔuppΔpMC1), GR167 harbored faster growth rate, higher transformation efficiency, increased intracellular reducing power level and higher heterologous protein productivity. Furthermore, the optimal chassis GR167 was engineered for enhanced surfactin production. Firstly, the iturin and fengycin biosynthetic gene clusters were deleted from GR167 to generate GR167ID. Subsequently, two strong promoters PRsuc and PRtpxi from LL3 were obtained by RNA-seq and promoter strength characterization, and then they were individually substituted for the native srfA promoter in GR167ID to generate GR167IDS and GR167IDT. The best mutant GR167IDS showed a 678-fold improvement in the transcriptional level of the srfA operon relative to GR167ID, and it produced 311.35 mg/L surfactin, with a 10.4-fold increase relative to GR167.Conclusions: The genome-reduced strain GR167 was advantageous over the parental strain in several industrially relevant physiological traits assessed and it was highlighted as an optimum chassis for enhanced surfactin production. In future studies, further reduction of the LL3 genome can be expected to create high-performance chassis for synthetic biology applications.
Geographic access and maternal health services utilization in Sélingué Health District, Mali.
Authors: TOUNKARA Moctar , Sangho Oumar , Beebe Madeleine , Whiting-Collins Lillian Joyce , Goins Rebecca R. , Marker Hannah C. , Winch Peter J. , Doumbia Seydou
Published: July 2020

Introduction. Maternal mortality is one of the main causes of death for women of childbearing age in Mali, and improving this outcome is slow, even in high geographic-access regions. Disparities in maternal health services utilization can constitute a major obstacle in the reduction of maternal mortality and denotes a lack of equity in the Malian health system.Literature on maternal health inequity has explored structural and individual factors influencing outcomes but has not examined inequities in health facility distribution within moderate geographic access districts in Mali. The purpose of this article is to examine disparities in education and geographic distance and how they affect utilization of maternal care within the Sélingué health district, a district with moderate geographic access to care, near Bamako, Mali.Methods. We conducted a cross sectional survey with cluster sampling in the Sélingué health district. Maternal health services characteristics and indicators were described. Association between dependent and independent variables was verified using Kendall’s tau-b correlation, Chi square, logistic regression with odds ratio and 95% confidence interval. Gini index and concentration curve were used to measure inequity.Results. The majority of the participants were 20 to 24 years old. Over 68% of our sample had some education, 65% completed at least four ANC visits, and 60.8% delivered at a health facility. Despite this evidence of healthcare access in Sélingué, disparities within the health district impede the other roughly 40% of our sample from utilizing maternal healthcare. The concentration index demonstrated the impact of inequity in geographic access comparing women residing near and far from the referral care facility.Conclusion. Maternal health services underutilization, within a district with moderate geographic access, indicates that deliberate attention should be paid to addressing geographic access even in such a district.
Interleukin-35 inhibited production of histamine and pro-inflammatory cytokines through suppression MAPKs pathway in HMC-1 cells
Authors: Chen Tao , Fu Lixin , Sun Qiaomei , Zhou Peimei , Guo Zai-pei
Published: July 2020

Background: IL-35 is a newly anti-inflammatory cytokine which belong to the IL-12 family. Mast cells, as one of the major effector cells in the immune response system, play important roles in the pathogenesis of chronic spontaneous urticarial (CSU). The aim of our study is to explore the inhibited role of IL-35 in HMC-1. Methods: The effects of IL-35 on cell proliferation, cytokine expression and histamine release in human mast cell line (HMC­1) were investigated by CCK8, ELISA or RT-PCR. The phosphorylation of ERK1/2, p38 and JNK1/2, in PMA and A23187 induced HMC-1 cells were detected by Western Blot.Results: We found that IL-35 significantly inhibited the proliferation of HMC-1 cells stimulated by PMA and A23187. IL-35 also down-regulates the released of histamine and the mRNA expression of IL-6 and IL-17 in activated HMC-1. Furthermore, IL-35 markedly inhibited the phosphorylation of ERK1/2, p38 and JNK1/2, in PMA and A23187 induced HMC-1 cells. Conclusions: This study provides first observations on the inhibitory and anti-inflammtory effect of IL-35 on activated HMC-1 cells. We suggest that IL35 may play an inhibited role in the pathogenesis of CSU.
The expression of the acarbose biosynthesis gene cluster in Actinoplanes sp. SE50/110 is dependent on the growth phase
Authors: Droste Julian , Ortseifen Vera , Schaffert Lena , Persicke Marcus , Schneiker-Bekel Susanne , Pühler Alfred , Kalinowski Jörn
Published: July 2020

Background: Actinoplanes sp. SE50/110 is the natural producer of the diabetes mellitus drug acarbose, which is highly produced during the growth phase and ceases during the stationary phase. In previous works, the growth-dependency of acarbose formation was assumed to be caused by a decreasing transcription of the acarbose biosynthesis genes during transition and stationary growth phase.Results: In this study, transcriptomic data using RNA-seq and state-of-the-art proteomic data from seven time points of controlled bioreactor cultivations were used to analyze expression dynamics during growth of Actinoplanes sp. SE50/110. A hierarchical cluster analysis revealed co-regulated genes, which display similar transcription dynamics over the cultivation time. Aside from the expected metabolic switch from primary to secondary metabolism during transition phase, we observed a significantly decreasing transcript abundance of all acarbose biosynthetic genes, with the strongest decrease for the monocistronically transcribed genes acbA, acbB, acbD and acbE. Our data confirm a similar trend for acb gene transcription and acarbose formation rate.Surprisingly, the proteome dynamics does not follow the respective transcription for all acb genes. This suggests different protein stabilities or post-transcriptional regulation of the Acb proteins, which in turn could indicate bottlenecks in the acarbose biosynthesis. Furthermore, several genes are co-expressed with the acb gene cluster over the course of the cultivation, including eleven transcriptional regulators (e.g. ACSP50_0424), two sigma factors (ACSP50_0644, ACSP50_6006) and further genes, which have not previously been in focus of acarbose research in Actinoplanes sp. SE50/110.Conclusion: In conclusion, we have demonstrated, that a genome wide transcriptome and proteome analysis in a high temporal resolution is well suited to study the acarbose biosynthesis and the transcriptional and post-transcriptional regulation thereof.
Identification of key pathways and hub genes in the myogenic process of pluripotent stem cell: A bioinformatics study
Authors: Fei Wenyong , Liu Mingsheng , Zhang Yao , Cao Shichao , Wang Xuanqi , Xie Bin , Wang Jingcheng
Published: July 2020

Purpose: The study aims to determine the process of myoginc differentiation in human pluripotent stem cells and to figure out that the key pathways and hub genes in the process, which do helpful for the further research of muscular regeneration.Method: Three gene expression profiles, GSE131125, GSE148994, GSE149055, about the comparisons of pluripotent stem cells and myogenic stem cells from the Gene Expression Omnibus (GEO) data base. Common differentially expressed genes (DEGs) were obtained and for the further analysis as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA analysis and protein‑protein interaction (PPI) network. In vitro cell research to verify the hub genes and key pathways.Result:824 DEGs were co-expressed in the three GSEs. 19 hub genes were identified from the PPI network. The GO and KEGG pathway analysis were performed to determine the functions of DEGs. GSEA analysis indicated the differentiated cells were enriched in muscle cell development and myogenesis.Conclusion: Our research revealed the main hub genes and modules in the myogeinc process of stem cells which contribute to further study about the molecular mechanism of myogenesis regeneration. Paving a way for more accurate treatment for muscle dysfunction.
Long-term Outcomes of the R3™ Delta Ceramic Acetabular System in Total Hip Arthroplasty
Authors: Davis Edward Thomas , Remes Ville , Virolainen Petri , Gebuhr Peter , Backlé Bart Van , Revell Matthew P. , Kopjar Branko
Published: July 2020

Background: Whilst bony fixation of hip replacement has stable solutions, there remains controversy over which bearing best optimizes longevity and function. Ceramic-on-ceramic (CoC) bearing combinations are associated with lower risk of revision due to aseptic loosening and dislocation. Evidence for long-term functional outcomes of modern, 4th generation CoC bearings is limited. The aim of this study was to analyze outcomes and complications of the R3™ Acetabular System (Smith & Nephew, Inc., Cordova, TN, USA) in combination with BIOLOX® Delta ceramic femoral head in patients undergoing primary total hip arthroplasty (THA).Methods: Between June 2009 and May 2011, 175 patients (178 hips) were enrolled into a prospective, study at 6 sites in Europe and prospectively followed-up at 3 months and 1, 3, 5, and 7 years postoperative. Results: Total WOMAC score improved from 63 (range, 22-91) preoperative to 8 (range, 0- 8) at 1-year follow-up and remained unchanged at 7-year follow-up. Modified Harris Hip Score improved from 45 (range, 10-87) preoperative to 83 (range, 25-100) at 3 months, 91 (range, 42-100) at 1 year, and 92 (range, 46, 100) at 7 years. UCLA Activity Rating Scale score improved from 3.3 (range, 1-8) preoperative to 6.2 (range, 2-8) at 1 year; it marginally declined to 5.8 (range, 3-8) at 7-year follow-up. There were 4 trochanteric fractures and 5 patients died of unrelated reasons. Three hips were revised (2 periprosthetic fractures and 1 subluxation). The 7-year cumulative survival rate was 98.3%. Conclusion: Clinical and functional improvements of THA with CoC bearing are maintained at 7 years postoperative.
Intraventricular haemorrhage in a Ugandan cohort of low birth weight neonates: The IVHU study
Authors: MacLeod Rachael , Paulson Joseph N , Okalany Noella , Okello Francis , Acom Linda , Ikiror Juliet , Cowan Frances M , Tann Cally J , Dyet Leigh E , Hagmann Cornelia F , Burgoine Kathy
Published: July 2020

Background Globally, 15 million neonates are born prematurely every year, over half in low income countries (LICs). Premature and low birth weight neonates have a higher risk of intraventricular haemorrhage (IVH). There are minimal data regarding IVH in sub-Saharan Africa. This study aimed to examine the incidence, severity and timing of and modifiable risk factors for IVH amongst low-birth-weight neonates in Uganda.Methods This is a prospective cohort study of neonates with birthweights of ≤2000g admitted to a neonatal unit (NNU) in a regional referral hospital in eastern Uganda. Maternal data were collected from interviews and medical records. Neonates had cranial ultrasound (cUS) scans on the day of recruitment and days 3, 7 and 28 after birth. Risk factors were tabulated and are presented alongside odds ratios (ORs) and adjusted odds ratios (aORs) for IVH incidence. Outcomes included incidence, timing and severity of IVH and 28-day survival. Results Overall, 120 neonates were recruited. IVH was reported in 34.2% of neonates; 19.2% had low grade (Papile grades 1-2) and 15% had high grade (Papile grades 3-4). Almost all IVH (90.2%) occurred by day 7, including 88.9% of high grade IVH. Of those with known outcomes, 70.4% (81/115) were alive on day 28 and survival was not associated with IVH. We found that vaginal delivery, gestational age (GA) <32 weeks, resuscitation in the NNU and being small for gestational age (SGA, <10th centile) increased the odds of IVH. Of the 6 neonates who received 2 doses of antenatal steroids, none had IVH. Conclusion In this resource limited NNU in eastern Uganda, more than a third of neonates born weighing ≤2000g had an IVH and the majority of these occurred by day 7. We found that vaginal birth, earlier gestation, being SGA and need for resuscitation after admission to the NNU increased the risk of IVH. This study had a high rate of SGA neonates and the risk factors and relationship of these factors with IVH in this setting needs further investigation. The role of antenatal steroids in the prevention of IVH in LICs also needs urgent exploration.
Recent Advances in the Development of Casein Kinase 1 Inhibitors
Authors: Li Sha-Sha , Dong Yue-Hui , Liu Zhao-Peng
Published: July 2020

Background:

The casein kinase 1 (CK1) family is involved in regulating many cellular
processes, including membrane trafficking, DNA damage repair, cytoskeleton dynamics,
cytoskeleton maintenance and apoptosis. CK1 isoforms, especially CK1δ and CK1ε have
emerged as important therapeutic targets for severe disorders such as Alzheimer’s disease
(AD), amyotrophic lateral sclerosis (ALS), familial advanced sleep phase syndrome and cancer.
Due to the importance of CK1 for the pathogenesis of disorders, there are great interests
in the development of CK1 inhibitors.

Method:

Using SciFinder® as a tool, the publications about the biology of CK1 and the recent
developments of CK1 inhibitors were surveyed with an exclusion of those published as
patents.

Results:

This review presents the current state of knowledge on the development of CK1 inhibitors,
including both synthetic small molecular inhibitors that were divided into 7 categories
according to structural features, and the natural compounds. An overview of the advancement
of CK1 inhibitors was given, with the introduction of various existing CK1 inhibitors,
their inhibitory activities, and the structure-activity relationships.

Conclusion:

Through physicochemical characterization and biological investigations, it is
possible to understand the structure-activity relationship of CK1 inhibitors, which will contribute
to better design and discovery of potent and selective CK1 inhibitors as potential
agents for severe disorders such as AD, ALS and cancer.
The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients
Authors: Okay Gülay , Koc Meliha Meric , Guler Eray Metin , Yabaci Ayşegül , Kocyigit Abdürrahim , Akkoyunlu Yasemin
Published: July 2020

Background:

Serum cytokine levels over the course of HIV infection usually increase
with immunosuppression and decrease after antiretroviral treatment (ART).

Objectives:

The aim of the study is to compare cytokine levels between HIV-infected patients (HIP)
and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine
levels.

Methods:

The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and
sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples
of HIP at the beginning and at month 6 of ART and in controls.

Results:

The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the
study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive
(p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was
lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002).
There was a positive correlation between the CD4+T cell count and serum concentration of IFN-
γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA
level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive
correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p>0.00).

Conclusions:

Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease
after ART, they were still significantly higher than the controls. IFN-γ responded differently
to ART compared to the other cytokines, indicating that it may play a distinct and important role in
the pathogenesis of HIV infection.
In Silico Investigation of the SARS CoV2 Protease with Thymoquinone, the Major Constituent of Nigella Sativa
Authors: Kadil Youness , Mouhcine Mohammed , Filali Houda
Published: July 2020

Introduction:

The COVID-19 caused by a new type of coronavirus has emerged from
China and led to thousands of deaths globally. Despite many groups engaged in studying the newly
emerged virus and searching for the treatment, the understanding of the SARS-CoV2 target ligand
interactions represents a key challenge. Several studies are being conducted to identify potential
treatment. Alternatively, the results of numerous studies have shown that protease inhibitors
can be a genuine leader in research. The antiviral activity and beneficial effect against respiratory
disorders of thymoquinone have been largely demonstrated.

Aim:

The aim of this study is to evaluate in silico the inhibition of the replication of SARS CoV2
by thymoquinone.

Methods:

This is a molecular simulation study using SARS CoV2 protease and thymoquinone
structures provided by Protein Data Bank.

Results:

The preliminary results have shown that thymoquinone may have inhibitory activities
against SARS CoV2 protease.

Conclusion:

Furthermore, given the demonstrated results of thymoquinone, we can conclude that
it may be considered as an effective or adjuvant treatment for SARS CoV2 infection.