bluuebunny/crossref_metadata_2025 huggingface dataset:
Preemptive intravenous iron therapy versus autologous whole blood therapy for early postoperative hemoglobin level in patients undergoing bimaxillary orthognathic surgery: a prospective randomized noninferiority trial
Authors: Chae Min Suk , Lee Mihyun , Choi Min Ho , Park Je Uk , Park Misun , Kim Young Hoon , Choi Hoon , Joo Jin , Moon Young Eun
Published: January 2021

Background

Previous studies have reported the efficacy and safety of intravenous (IV) iron therapy during the perioperative period as an alternative and adjunct to allogeneic blood transfusion. Preemptive IV iron therapy provides noninferior hemoglobin levels on postoperative day (POD) 1 compared to autologous whole blood therapy (AWBT) in healthy patients who had undergone bimaxillary orthognathic surgery.

Methods

This was a prospective, patient-randomized, noninferiority trial. After excluding 2 patients, 64 patients were divided into two groups: the IV iron therapy group (patients received IV iron infusion 4 weeks before surgery; n = 32) and the AWBT group (2 units of autologous whole blood were collected 4 and 2 weeks before surgery; n = 32). The primary outcome was hemoglobin level on POD 1 and the prespecified noninferiority limit was − 1 g/dL.

Results

Baseline data were comparable, including hemoglobin and iron levels, between the two groups. Immediately before surgery, the levels of hemoglobin, iron, and ferritin were higher in the IV iron group than in the AWBT group. The mean treatment difference (iron group—whole blood group) in hemoglobin level on POD 1 between the two groups was 0.09 (95% CI = − 0.83 to 1.0). As the lower limit of the 95% CI (− 0.83) was higher than the prespecified noninferiority margin (δ = − 1), noninferiority was established. On POD 2, the hemoglobin level became lower in the iron group, which eventually led to greater requirement of allogeneic blood transfusion compared to the whole blood group. However, the iron group did not require allogeneic blood transfusion during or early after surgery, and the whole blood group showed continuously higher incidence of overt iron deficiency compared to the iron group.

Conclusion

As collection of autologous whole blood caused overt iron loss and anemia before surgery and intraoperative transfusion of whole blood was not able to prevent the occurrence of persistent iron deficiency after surgery, IV iron therapy was found to have potential benefits for iron homeostasis and subsequent erythropoiesis in healthy patients early after bimaxillary orthognathic surgery.

Trial registration: Clinical Research Information Service, Republic of Korea, approval number: KCT0003680 on March 27, 2019. https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15769&sLeft=2<ype=my&rtype=my.
Piperlongumine inhibits the growth of non-small cell lung cancer cells via the miR-34b-3p/TGFBR1 pathway
Authors: Lu Xinhua , Xu Chenyang , Xu Zhexuan , Lu Chunya , Yang Rui , Zhang Furui , Zhang Guojun
Published: January 2021

Background

Non-small cell lung cancer is a common type of lung cancer. Piperlongumine (PL), which is extracted from the roots of piperaceae plant, long pepper, and peppercorn, is an alkaloid amide that inhibits tumor growth and metastasis. However, whether it affects lung cancer cells remains unclear.

Methods

We assessed the effects of PL on the proliferation and apoptosis of A549 and H1299 NSCLC cell lines.

Results

PL was mildly toxic to normal human bronchial epithelial cells and significantly suppressed growth and facilitated apoptosis of A549 and H1299 cells. It also upregulated microRNA (miR)-34b-3p and downregulated the transforming growth factor beta type I receptor (TGFBR1). The dual-luciferase reporter assay showed that TGFBR1 is a target gene of miR-34b-3p. Silencing of miR-34b-3p or overexpression of TGFBR1 partially attenuated the effects of PL on A549 and H1299 cells.

Conclusions

PL inhibits proliferation and induces apoptosis of A549 and H1299 cells by upregulating miR-34b-3p and modulating TGFBR1 signaling pathway.
Suppression of autophagy through JAK2/STAT3 contributes to the therapeutic action of rhynchophylline on asthma
Authors: Li Hui , Bi Qianyu , Cui Hongxia , Lv Chuanfeng , Wang Meng
Published: January 2021

Background

Asthma is a chronic inflammatory disease characterized by airway remodeling and inflammation. Rhynchophylline is a kind of indole alkaloid isolated fromUncaria rhynchophylla. Here we investigated the effect of rhynchophylline on autophagy in asthma.

Methods

A mice model of asthma was established by ovalbumin challenge. Histopathological changes were assessed by hematoxylin-eosin staining, periodic acid-schiff staining and Masson staining. The levels of IgE in serum, interleukin-6 and interleukin-13 in bronchoalveolar lavage fluid, as well as the activities of superoxide dismutase and catalase in lung tissues were detected. The expression of autophagy-related genes and Janus kinase (JAK) 2/ signal transducer and activator of transcription (STAT) 3 signal was detected by western blot and immunofluorescence. Airway smooth muscle cells (ASMCs) were isolated, and the effect rhynchophylline on autophagy in ASMCs was explored.

Results

Our data showed that rhynchophylline treatment alleviated inflammation, airway remodeling, and oxidative stress in asthma. In addition, autophagy, which was implicated in asthma, was suppressed by rhynchophylline with decreased level of autophagy-related proteins. Furthermore, rhynchophylline suppressed the JAK2/STAT3 signaling pathway, which was activated in asthma. In vitro study showed that rhynchophylline suppressed ASMC autophagy through suppressing the activation of JAK2/STAT3 signal.

Conclusions

Our study demonstrated that rhynchophylline can alleviate asthma through suppressing autophagy in asthma, and that JAK2/STAT3 signal was involved in this effect of rhynchophylline. This study indicates that rhynchophylline may become a promising drug for the treatment of asthma.
Norwogonin attenuates hypoxia-induced oxidative stress and apoptosis in PC12 cells
Authors: Jing Linlin , Gao Rongmin , Zhang Jie , Zhang Dongmei , Shao Jin , Jia Zhengping , Ma Huiping
Published: January 2021

Background

Norwogonin is a natural flavone with three phenolic hydroxyl groups in skeletal structure and has excellent antioxidant activity. However, the neuroprotective effect of norwogonin remains unclear. Here, we investigated the protective capacity of norwogonin against oxidative damage elicited by hypoxia in PC12 cells.

Methods

The cell viability and apoptosis were examined by MTT assay and Annexin V-FITC/PI staining, respectively. Reactive oxygen species (ROS) content was measured using DCFH-DA assay. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and antioxidant enzyme levels were determined using commercial kits. The expression of related genes and proteins was measured by real-time quantitative PCR and Western blotting, respectively.

Results

We found that norwogonin alleviated hypoxia-induced injury in PC12 cells by increasing the cell viability, reducing LDH release, and ameliorating the changes of cell morphology. Norwogonin also acted as an antioxidant by scavenging ROS, reducing MDA production, maintaining the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and decreasing the expression levels of HIF-1α and VEGF. In addition, norwogonin prevented cell apoptosis via inhibiting the expression levels of caspase-3, cytochrome c and Bax, while increasing the expression levels of Bcl-2 and the ratio of Bcl-2/Bax.

Conclusions

Norwogonin attenuates hypoxia-induced injury in PC12 cells by quenching ROS, maintaining the activities of antioxidant enzymes, and inhibiting mitochondrial apoptosis pathway.
The effectiveness and safety of Tai Chi for patients with essential hypertension: study protocol for an open-label single-center randomized controlled trial
Authors: Li Yuxi , Zhong Dongling , Dong Chao , Shi Lihong , Zheng Yaling , Liu Yongguo , Li Qiaoqin , Zheng Hui , Li Juan , Liu Tianyu , Jin Rongjiang
Published: January 2021

Background

Evidence showed that Tai Chi may have beneficial effects among hypertensive individuals, although the results are not convincing. We aim to conduct a high-quality clinical trial with 24-h BP measurement to provide robust evidence of Tai Chi for essential hypertension.

Methods

This is an open-label single-center randomized controlled trial with 3 parallel arms. We will compare Tai Chi with walking and waiting-list control. We will recruit 234 hypertensive patients with mild to moderate essential hypertension and randomly assign them to 3 different groups. Participants in Tai Chi group will receive a group-format Yang style 24-form Tai Chi exercise program, 3 sessions per week for 12 weeks. The walking group will be asked to walk, 3 sessions per week for 12 weeks. The waiting-list group will not receive any interventions and/or exercise training. The primary outcome is the change in average 24-h systolic blood pressure (SBP) between baseline and 12 weeks after randomization. The secondary outcomes include 24-h Diastolic Blood Pressure (DBP), average SBP and average DBP during the daytime and night-time, blood pressure (BP) variability, SBP load and DBP load, circadian rhythm of BP, and morning BP surge, endothelial functional indicators, home measured BP, quality of life, adverse events and so on.

Discussion

We expect findings of this trial will provide important insight into application of Tai Chi as an effective and acceptable method for hypertensive patients. Successful completion of this proposed study will also contribute to promotion of Tai Chi in the community in the future.

Trial registration

Clinicaltrials.gov registry: https://clinicaltrials.gov/ct2/show/NCT04267471, date: February 12, 2020.
Simulation-based curriculum development: lessons learnt in Global Health education
Authors: Sawaya Rasha D. , Mrad Sandra , Rajha Eva , Saleh Rana , Rice Julie
Published: January 2021

Background

Simulation based medical education (SBME) allows learners to acquire clinical skills without exposing patients to unnecessary risk. This is especially applicable to Emergency Medicine training programs where residents are expected to demonstrate proficiency in the management of time critical, low frequency, and highly-morbidity conditions. This study aims to describe the process through which a SBME curriculum was created, in a limited simulation resource setting at a 4-year Emergency Medicine (EM) residency program at the American University of Beirut Medical Center.

Methods

A case-based pilot simulation curriculum was developed following Kern’s 6 step approach to curriculum design. The curricular objectives were identified through an anonymous survey of the program’s residents and faculty. Curriculum outcomes were assessed, and the curriculum was revised to address curricular barriers. Evaluations of the revised curriculum were collected during the simulation sessions and through a whole revised curriculum evaluation at the end of the first year of its implementation.

Results

14/20 residents (70%) and 8/8 faculty (100%) completed the needs assessment from which objectives for the pilot curriculum were developed and implemented through 6 2-h sessions over a 1-year period. Objectives were not met and identified barriers included cost, scheduling, resources, and limited faculty time. The revised curriculum addressed these barriers and 24 40-min sessions were successfully conducted during the following year. The sessions took place 3 at a time, in 2-h slots, using the same scenario to meet the objectives of the different learners’ levels. 91/91 evaluations were collected from participants with overall positive results. The main differences between the pilot and the revised curricula included: a better understanding of the simulation center resources and faculty’s capabilities.

Conclusion

Simulation-based education is feasible even with limited-resources. However, understanding the resources available, and advocating for protected educator time are essential to implementing a successful EM simulation curriculum.
Closing the knowledge gap in pelvic neuroanatomy: assessment of a cadaveric training program
Authors: Marcu Ioana , Balica Adrian , Gavard Jeffrey A. , Campian Eugen C. , Fernandes Gustavo Leme , Solnik M. Jonathon , Morozov Vadim , Lemos Nucelio
Published: January 2021

Background

The objective of this study is to characterize participants in a laparoscopic cadaveric neuroanatomy course and assess knowledge of pelvic neuroanatomy before and after this course.

Methods

This is a survey-based cohort study with a setting in a university educational facility. The participants are surgeons in a multiday laparoscopic cadaveric pelvic neuroanatomy course. Participants completed a precourse survey, including demographics and comfort with laparoscopic surgery. They then completed an identical precourse and postcourse anatomic knowledge test. Main outcomes are scores on the anatomic knowledge test precourse and postcourse.

Results

44 respondents were included: 25 completed fellowship, 15 completed residency, 2 were residents, and 2 were fellows. Participants were on average 11.09 years post training, with an average of 8.67 years from training if they completed fellowship and 18.62 years if they completed residency only. 22 of 42 respondents strongly agreed or agreed they are comfortable performing complex laparoscopic hysterectomies. The average precourse score was 32.18/50 points and the mean difference score (MDS, defined as mean of Postcourse scores minus Precourse scores) was 9.80, showing significant improvement (p <  0.001). Precourse and MDS scores were not significantly different when comparing country of practice, level of training, or time since training.

Conclusion

Baseline knowledge of pelvic neuroanatomy was similar among groups when comparing fellowship status, place of training, or time since training. There was significant improvement in knowledge after training in this dissection method. This course garnered interest from surgeons with broad training backgrounds.
Leadership curricula and assessment in Australian and New Zealand medical schools
Authors: Ross Simone Jacquelyn , Sen Gupta Tarun , Johnson Peter
Published: January 2021

Background

The Australian Medical Council, which accredits Australian medical schools, recommends medical leadership graduate outcomes be taught, assessed and accredited. In Australia and New Zealand (Australasia) there is a significant research gap and no national consensus on how to educate, assess, and evaluate leadership skills in medical professional entry degree/programs. This study aims to investigate the current curricula, assessment and evaluation of medical leadership in Australasian medical degrees, with particular focus on the roles and responsibilities of medical leadership teachers, frameworks used and competencies taught, methods of delivery, and barriers to teaching leadership.

Methods

A self-administered cross-sectional survey was distributed to senior academics and/or heads or Deans of Australasian medical schools. Data for closed questions and ordinal data of each Likert scale response were described via frequency analysis. Content analysis was undertaken on free text responses and coded manually.

Results

Sixteen of the 22 eligible (73%) medical degrees completed the full survey and 100% of those indicate that leadership is taught in their degree. In most degrees (11, 69%) leadership is taught as a common theme integrated throughout the curricula across several subjects. There is a variety of leadership competencies taught, with strengths being communication (100%), evidence based practice (100%), critical reflective practice (94%), self-management (81%), ethical decision making (81%), critical thinking and decision making (81%). Major gaps in teaching were financial management (20%), strategic planning (31%) and workforce planning (31%). The teaching methods used to deliver medical leadership within the curricula are diverse, with many degrees providing opportunities for leadership teaching for students outside the curricula. Most degrees (10, 59%) assess the leadership education, with one-third (6, 35%) evaluating it.

Conclusions

Medical leadership competencies are taught in most degrees, but key leadership competencies are not being taught and there appears to be no continuous quality improvement process for leadership education. There is much more we can do as medical educators, academics and leaders to shape professional development of academics to teach medical leadership, and to agree on required leadership skills set for our students so they can proactively shape the future of the health care system.
Computational analysis to repurpose drugs for COVID-19 based on transcriptional response of host cells to SARS-CoV-2
Authors: Li Fuhai , Michelson Andrew P. , Foraker Randi , Zhan Ming , Payne Philip R. O.
Published: January 2021

Background

The Coronavirus Disease 2019 (COVID-19) pandemic has infected over 10 million people globally with a relatively high mortality rate. There are many therapeutics undergoing clinical trials, but there is no effective vaccine or therapy for treatment thus far. After affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), molecular signaling pathways of host cells play critical roles during the life cycle of SARS-CoV-2. Thus, it is significant to identify the involved molecular signaling pathways within the host cells. Drugs targeting these molecular signaling pathways could be potentially effective for COVID-19 treatment.

Methods

In this study, we developed a novel integrative analysis approach to identify the related molecular signaling pathways within host cells, and repurposed drugs as potentially effective treatments for COVID-19, based on the transcriptional response of host cells.

Results

We identified activated signaling pathways associated with the infection caused SARS-CoV-2 in human lung epithelial cells through integrative analysis. Then, the activated gene ontologies (GOs) and super GOs were identified. Signaling pathways and GOs such as MAPK, JNK, STAT, ERK, JAK-STAT, IRF7-NFkB signaling, and MYD88/CXCR6 immune signaling were particularly activated. Based on the identified signaling pathways and GOs, a set of potentially effective drugs were repurposed by integrating the drug-target and reverse gene expression data resources. In addition to many drugs being evaluated in clinical trials, the dexamethasone was top-ranked in the prediction, which was the first reported drug to be able to significantly reduce the death rate of COVID-19 patients receiving respiratory support.

Conclusions

The integrative genomics data analysis and results can be helpful to understand the associated molecular signaling pathways within host cells, and facilitate the discovery of effective drugs for COVID-19 treatment.
Participation in the Cardiovascular Health Awareness Program (CHAP) by older adults residing in social housing in Quebec: Social network analysis
Authors: Deville-Stoetzel Nadia , Kaczorowski Janusz , Agarwal Gina , Lussier Marie-Thérèse , Girard Magali
Published: January 2021

Background

The Cardiovascular Health Awareness Program (CHAP) is as a community-based cardiovascular disease prevention program recently adapted to target older adults living in 14 social housing buildings in Ontario (7) and Quebec (7). Social network analysis (SNA) has been used successfully to assess and strengthen participation in health promotion programs. We applied SNA methods to investigate whether interpersonal relationships among residents within buildings influenced their participation in CHAP.

Methods

Our aim was to examine relational dynamics in two social housing buildings in Quebec with low and high CHAP attendance rates, respectively. We used sociometric questionnaires and network analysis for the quantitative phase of the study, supplemented by a phase of qualitative interviews. All residents of both buildings were eligible for the sociometric questionnaire. Respondents for the qualitative interviews were purposively selected to represent the different attendance situations following the principle of content saturation.

Results

In total, 69 residents participated in the study, 37 through sociometric questionnaires and 32 in qualitative interviews. Of the latter, 10 attended almost all CHAP sessions, 10 attended once, and 12 attended none. Results of the quantitative analysis phase identified well-known and appreciated local leaders. In Building 1, which had a high attendance rate (34.3%), there was a main leader (in-degree or ‘named by others’ frequency 23.2%) who had attended all CHAP sessions. In Building 2, which had a low attendance rate (23.9%), none of the leaders had attended CHAP sessions. Results of the qualitative analysis phase showed that residents who did not attend CHAP sessions (or other activities in the building) generally preferred to avoid conflicts, vindictiveness, and gossip and did not want to get involved in clans and politics within their building.

Conclusion

We identified four potential strategies to increase attendance at CHAP sessions by residents of subsidized housing for older adults: strengthen confidentiality for those attending the sessions; use community peer networks to enhance recruitment; pair attendees to increase the likelihood of participation; and intervene through opinion leaders or bridging individuals.
Genome-wide survey of tandem repeats by nanopore sequencing shows that disease-associated repeats are more polymorphic in the general population
Authors: Mitsuhashi Satomi , Frith Martin C. , Matsumoto Naomichi
Published: January 2021

Background

Tandem repeats are highly mutable and contribute to the development of human disease by a variety of mechanisms. It is difficult to predict which tandem repeats may cause a disease. One hypothesis is that changeable tandem repeats are the source of genetic diseases, because disease-causing repeats are polymorphic in healthy individuals. However, it is not clear whether disease-causing repeats are more polymorphic than other repeats.

Methods

We performed a genome-wide survey of the millions of human tandem repeats using publicly available long read genome sequencing data from 21 humans. We measured tandem repeat copy number changes using . Length variation of known disease-associated repeats was compared to other repeat loci.

Results

We found that known Mendelian disease-causing or disease-associated repeats, especially CAG and 5′UTR GGC repeats, are relatively long and polymorphic in the general population. We also show that repeat lengths of two disease-causing tandem repeats, inATXN3andGLS, are correlated with near-by GWAS SNP genotypes.

Conclusions

We provide a catalog of polymorphic tandem repeats across a variety of repeat unit lengths and sequences, from long read sequencing data. This method especially if used in genome wide association study, may indicate possible new candidates of pathogenic or biologically important tandem repeats in human genomes.
Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study
Authors: Rau Matthias , Thiele Kirsten , Hartmann Niels-Ulrik Korbinian , Schuh Alexander , Altiok Ertunc , Möllmann Julia , Keszei András P. , Böhm Michael , Marx Nikolaus , Lehrke Michael
Published: January 2021

Background

In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggest that immediate hemodynamic effects may play a role. However, hitherto no data exist on early effects of SGLT2 inhibitors on hemodynamic parameters and cardiac function. Thus, this study examined early and delayed effects of empagliflozin treatment on hemodynamic parameters including systemic vascular resistance index, cardiac index, and stroke volume index, as well as echocardiographic measures of cardiac function.

Methods

In this placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized to empagliflozin 10 mg or placebo for a period of 3 months. Hemodynamic and echocardiographic parameters were assessed after 1 day, 3 days and 3 months of treatment.

Results

Baseline characteristics were not different in the empagliflozin (n = 22) and placebo (n = 20) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 h; day 1: 48.4 ± 34.7 g/24 h; p < 0.001) as well as urinary volume (1740 ± 601 mL/24 h to 2112 ± 837 mL/24 h; p = 0.011) already after one day compared to placebo. Treatment with empagliflozin had no effect on the primary endpoint of systemic vascular resistance index, nor on cardiac index, stroke volume index or pulse rate at any time point. In addition, echocardiography showed no difference in left ventricular systolic function as assessed by left ventricular ejections fraction and strain analysis. However, empagliflozin significantly improved left ventricular filling pressure as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/eʹ) which became significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p = 0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/s; day 1: 0.73 ± 0.2 m/sec; p = 0.003).

Conclusions

Empagliflozin treatment of patients with T2D has no significant effect on hemodynamic parameters after 1 or 3 days, nor after 3 months, but leads to rapid and sustained significant improvement of diastolic function.

Trial registration EudraCT Number: 2016-000172-19; date of registration: 2017-02-20 (clinicaltrialregister.eu)
Study on the isoprene-producing co-culture system of Synechococcus elongates–Escherichia coli through omics analysis
Authors: Liu Hui , Cao Yujin , Guo Jing , Xu Xin , Long Qi , Song Lili , Xian Mo
Published: January 2021

Background

The majority of microbial fermentations are currently performed in the batch or fed-batch manner with the high process complexity and huge water consumption. The continuous microbial production can contribute to the green sustainable development of the fermentation industry. The co-culture systems of photo-autotrophic and heterotrophic species can play important roles in establishing the continuous fermentation mode for the bio-based chemicals production.

Results

In the present paper, the co-culture system of Synechococcus elongates–Escherichia coli was established and put into operation stably for isoprene production. Compared with the axenic culture, the fermentation period of time was extended from 100 to 400 h in the co-culture and the isoprene production was increased to eightfold. For in depth understanding this novel system, the differential omics profiles were analyzed. The responses of BL21(DE3) to S. elongatus PCC 7942 were triggered by the oxidative pressure through the Fenton reaction and all these changes were linked with one another at different spatial and temporal scales. The oxidative stress mitigation pathways might contribute to the long-lasting fermentation process. The performance of this co-culture system can be further improved according to the fundamental rules discovered by the omics analysis.

Conclusions

The isoprene-producing co-culture system of S. elongates–E. coli was established and then analyzed by the omics methods. This study on the co-culture system of the model S. elongates–E. coli is of significance to reveal the common interactions between photo-autotrophic and heterotrophic species without natural symbiotic relation, which could provide the scientific basis for rational design of microbial community.
Effect of overexpression of SNF1 on the transcriptional and metabolic landscape of baker’s yeast under freezing stress
Authors: Meng Lu , Yang Xu , Lin Xue , Jiang Huan-Yuan , Hu Xiao-Ping , Liu Si-Xin
Published: January 2021

Background

Freezing stress is the key factor that affecting the cell activity and fermentation performance of baker’s yeast in frozen dough production. Generally, cells protect themselves from injury and maintain metabolism by regulating gene expression and modulating metabolic patterns in stresses. The Snf1 protein kinase is an important regulator of yeast in response to stresses. In this study, we aim to study the role of the catalytic subunit of Snf1 protein kinase in the cell tolerance and dough leavening ability of baker’s yeast during freezing. Furthermore, the effects of SNF1 overexpression on the global gene expression and metabolite profile of baker’s yeast before and after freezing were analysed using RNA-sequencing and untargeted UPLC − QTOF-MS/MS, respectively.

Results

The results suggest that overexpression of SNF1 was effective in enhancing the cell tolerance and fermentation capacity of baker’s yeast in freezing, which may be related to the upregulated proteasome, altered metabolism of carbon sources and protectant molecules, and changed cell membrane components. SNF1 overexpression altered the level of leucin, proline, serine, isoleucine, arginine, homocitrulline, glycerol, palmitic acid, lysophosphatidylcholine (LysoPC), and lysophosphatidylethanolamine (LysoPE) before freezing, conferring cells resistance in freezing. After freezing, relative high level of proline, lysine, and glycerol maintained by SNF1 overexpression with increased content of LysoPC and LysoPE.

Conclusions

This study will increase the knowledge of the cellular response of baker’s yeast cells to freezing and provide new opportunities for the breeding of low-temperature resistant strains.
CircRNA PIP5K1A promotes the progression of glioma through upregulation of the TCF12/PI3K/AKT pathway by sponging miR-515-5p
Authors: Zheng Kebin , Xie Haipeng , Wu Wensong , Wen Xichao , Zeng Zhaomu , Shi Yanfang
Published: January 2021

Background

Increasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A, in glioma.

Methods

Firstly, reverse transcription-polymerase chain reaction (RT-PCR) was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical-pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and CircPIP5K1A overexpression and knockdown cell models were constructed. Subsequently, cell proliferation and viability were detected by the CCK8 method and BrdU staining. Cell apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (Caspase3, Bax, and Bcl2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, and N-cadherin) was determined by western blot or RT-PCR.

Results

The results manifested that CircPIP5K1A was upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated glioma cell proliferation, invasion, and EMT and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A upregulated TCF12 and PI3K/AKT activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3′-untranslated region (UTR) of TCF12.

Conclusions

Overall, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates glioma evolvement by modulating the miR-515-5p-mediated TCF12/PI3K/AKT axis.
Suppression of TCAB1 expression induced cellular senescence by lessening proteasomal degradation of p21 in cancer cells
Authors: Niu Jing , Gao Rui-Qi , Cui Meng-Tian , Zhang Chen-Guang , Li Shen-Tao , Cheng Shan , Ding Wei
Published: January 2021

Background

TCAB1, a.k.a. WRAP53β or WDR79, is an important molecule for the maintenance of Cajal bodies and critically involved in telomere elongation and DNA repair. Upregulation of TCAB1 were discovered in a variety types of cancers. However, the function of TCAB1 in tumor cell senescence remains absent.

Methods

The TCAB1 knockdown cell lines were constructed. The expression levels of TCAB1, p21, p16 and p53 were detected by qRT-PCR and western blotting. Staining of senescence-associated β-galactosidase was used to detect senescent cells. The ubiquitination of the p21 was analysed by immunoprecipitation and in vivo ubiquitination assay. TCGA databases were employed to perform in silico analyses for the mRNA expression of TCAB1, p21, p16 and p53.

Results

Here, we discovered that knockdown of TCAB1 induced rapid progression of cellular senescence in A549, H1299 and HeLa cells. In exploiting the mechanism underlining the role of TCAB1 on senescence, we found a significant increase of p21 at the protein levels upon TCAB1 depletion, whereas the p21 mRNA expression was not altered. We verified that TCAB1 knockdown was able to shunt p21 from proteasomal degradation by regulating the ubiquitination of p21. In rescue assays, it was demonstrated that decreasing the expression of p21 or increasing the expression of TCAB1 were able to attenuate the cellular senescence process induced by TCAB1 silencing.

Conclusions

This study revealed the importance of TCAB1 for its biological functions in the regulation of cell senescence. Our results will be helpful to understand the mechanisms of senescence in cancer cells, which could provide clues for designing novel strategies for developing effective treatment regimens.
Multi-view 3D skin feature recognition and localization for patient tracking in spinal surgery applications
Authors: Manni Francesca , Mamprin Marco , Holthuizen Ronald , Shan Caifeng , Burström Gustav , Elmi-Terander Adrian , Edström Erik , Zinger Svitlana , de With Peter H. N.
Published: January 2021

Background

Minimally invasive spine surgery is dependent on accurate navigation. Computer-assisted navigation is increasingly used in minimally invasive surgery (MIS), but current solutions require the use of reference markers in the surgical field for both patient and instruments tracking.

Purpose

To improve reliability and facilitate clinical workflow, this study proposes a new marker-free tracking framework based on skin feature recognition.

Methods

Maximally Stable Extremal Regions (MSER) and Speeded Up Robust Feature (SURF) algorithms are applied for skin feature detection. The proposed tracking framework is based on a multi-camera setup for obtaining multi-view acquisitions of the surgical area. Features can then be accurately detected using MSER and SURF and afterward localized by triangulation. The triangulation error is used for assessing the localization quality in 3D.

Results

The framework was tested on a cadaver dataset and in eight clinical cases. The detected features for the entire patient datasets were found to have an overall triangulation error of 0.207 mm for MSER and 0.204 mm for SURF. The localization accuracy was compared to a system with conventional markers, serving as a ground truth. An average accuracy of 0.627 and 0.622 mm was achieved for MSER and SURF, respectively.

Conclusions

This study demonstrates that skin feature localization for patient tracking in a surgical setting is feasible. The technology shows promising results in terms of detected features and localization accuracy. In the future, the framework may be further improved by exploiting extended feature processing using modern optical imaging techniques for clinical applications where patient tracking is crucial.
Maternal education and equity in breastfeeding: trends and patterns in 81 low- and middle-income countries between 2000 and 2019
Authors: Neves Paulo A. R. , Barros Aluisio J. D. , Gatica-Domínguez Giovanna , Vaz Juliana S. , Baker Phillip , Lutter Chessa K.
Published: January 2021

Background

In low- and middle-income countries (LMICs), low levels of formal maternal educational are positively associated with breastfeeding whereas the reverse is true among women with higher levels of formal education. As such, breastfeeding has helped to reduce health equity gaps between rich and poor children. Our paper examines trends in breastfeeding and formula consumption by maternal educational in LMICs over nearly two decades.

Methods

We used 319 nationally representative surveys from 81 countries. We used WHO definitions for breastfeeding indicators and categorized maternal education into three categories: none, primary, and secondary or higher. We grouped countries according to the World Bank income groups and UNICEF regions classifications. The trend analyses were performed through multilevel linear regression to obtain average absolute annual changes in percentage points.

Results

Significant increases in prevalence were observed for early initiation and exclusive breastfeeding across all education categories, but more prominently in women with no formal education for early breastfeeding and in higher level educated women for exclusive breastfeeding. Small decreases in prevalence were seen mostly for women with no formal education for continued breastfeeding at 1 and 2 years. Among formula indicators, only formula consumption between 6 and 23 months decreased significantly over the period for women with primary education. Analysis by world regions demonstrated that gains in early and exclusive breastfeeding were almost universally distributed among education categories, except in the Middle East and North Africa where they decreased throughout education categories. Continued breastfeeding at 1 and 2 years increased in South Asia, Latin America and the Caribbean, and Eastern Europe and Central Asia for primary or higher education categories. Declines occurred for the group of no formal education in South Asia and nearly all education categories in the Middle East and North Africa with a decline steeper for continued breastfeeding at 2 years. With a few exceptions, the use of formula is higher among children of women at the highest education level in all regions.

Conclusions

Over the course of our study, women with no formal education have worsening breastfeeding indicators compared to women with primary and secondary or higher education.
Regional inequality in the Janani Suraksha Yojana coverage in India: a geo-spatial analysis
Authors: Mishra Prem Shankar , Kumar Pradeep , Srivastava Shobhit
Published: January 2021

Introduction

Although India has made significant progress in institutional delivery after the implementation of the National Rural Health Mission under which the Janani Suraksha Yojana (JSY) is a sub-programme which played a vital role in the increase of institutional delivery in public facilities. Therefore, this paper aims to provide an understanding of the JSY coverage at the district level in India. Further, it tries to carve out the factors responsible for the regional disparity of JSY coverage at district levels.

Methods

The study used the National Family Health Survey data, which is a cross-sectional survey conducted in 2015–16, India. The sample size of this study was 148,145 women aged 15–49 years who gave last birth in the institution during 5 years preceding the survey. Bivariate and multivariate regression analysis was used to fulfill the study objectives. Additionally, Moran’s I statistics and bivariate Local Indicator for Spatial Association (LISA) maps were used to understand spatial dependence and clustering of JSY coverage. Ordinary least square, spatial lag and spatial error models were used to examine the correlates of JSY utilization.

Results

The value of spatial-autocorrelation for JSY was 0.71 which depicts the high dependence of the JSY coverage over districts of India. The overall coverage of JSY in India is 36.4% and it highly varied across different regions, districts, and even socioeconomic groups. The spatial error model depicts that if in a district the women with no schooling status increase by 10% then the benefits of JSY get increased by 2.3%. Similarly, if in a district the women from poor wealth quintile, it increases by 10% the benefits of JSY also increased by 4.6%. However, the coverage of JSY made greater imperative to understand it due to its clustering among districts of specific states only.

Conclusion

It is well reflected in the EAGs states in terms of spatial-inequality in service coverage. There is a need to universalize the JSY programme at a very individual level. And, it is required to revisit the policy strategy and the implementation plans at regional or district levels.
Sex-dependent dysregulation of human neutrophil responses by bisphenol A
Authors: Ratajczak-Wrona Wioletta , Garley Marzena , Rusak Malgorzata , Nowak Karolina , Czerniecki Jan , Wolosewicz Katarzyna , Dabrowska Milena , Wolczynski Slawomir , Radziwon Piotr , Jablonska Ewa
Published: January 2021

Background

In the present study, we aimed to investigate selected functions of human neutrophils exposed to bisphenol A (BPA) under in vitro conditions. As BPA is classified among xenoestrogens, we compared its action and effects with those of 17β-estradiol (E2).

Methods

Chemotaxis of neutrophils was examined using the Boyden chamber. Their phagocytosis and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity were assessed via Park’s method with latex beads and Park’s test with nitroblue tetrazolium. To assess the total concentration of nitric oxide (NO), the Griess reaction was utilized. Flow cytometry was used to assess the expression of cluster of differentiation (CD) antigens. The formation of neutrophil extracellular traps (NETs) was analyzed using a microscope (IN Cell Analyzer 2200 system). Expression of the investigated proteins was determined using Western blot.

Results

The analysis of results obtained for both sexes demonstrated that after exposure to BPA, the chemotactic capacity of neutrophils was reduced. In the presence of BPA, the phagocytic activity was found to be elevated in the cells obtained from women and reduced in the cells from men. Following exposure to BPA, the percentage of neutrophils with CD14 and CD284 (TLR4) expression, as well as the percentage of cells forming NETs, was increased in the cells from both sexes. The stimulatory role of BPA and E2 in the activation of NADPH oxidase was observed only in female cells. On the other hand, no influence of E2 on the expression of CD14 and CD284, chemotaxis, phagocytosis, and the amount of NET-positive neutrophils was found for both sexes. The study further showed that BPA intensified NO production and iNOS expression in the cells of both sexes. In addition, intensified expression of all tested PI3K-Akt pathway proteins was observed in male neutrophils.

Conclusions

The study demonstrated the influence of BPA on neutrophil functions associated with locomotion and pathogen elimination, which in turn may disturb the immune response of these cells in both women and men. Analysis of the obtained data showed that the effect of this xenoestrogen on the human neutrophils was more pronounced than E2.
A comparability study of natural and deglycosylated PD-L1 levels in lung cancer: evidence from immunohistochemical analysis
Authors: Mei Jie , Xu Junying , Yang Xuejing , Gu Dingyi , Zhou Weijian , Wang Huiyu , Liu Chaoying
Published: January 2021

Emerging evidence has revealed that the removal of N-linked glycosylation could enhance PD-L1 detection. However, whether PD-L1 antibodies against different epitopes of PD-L1 antigens responding to deglycosylation has not been characterized. In this study, we compared natural and deglycosylated PD-L1 expression in lung cancer (LuCa) using a panel of PD-L1 antibodies (28–8, CAL10, 73–10 and SP142). We found that removal of N-linked glycosylation markedly enhanced PD-L1 detection when the 28–8, CAL10 and SP142 monoclonal antibodies (mAbs) were used but slightly inhibited PD-L1 detection when the 73–10 mAb was used. Moreover, for the CAL10 and SP142 mAbs, deglycosylated PD-L1 levels showed stronger correlations with the response to anti-PD-1 therapy. Overall, our research provides a comprehensive insight into the application of deglycosylated PD-L1 detection, which expands the clinical significance of this established strategy in LuCa.
Surface charge modulation of rifampicin-loaded PLA nanoparticles to improve antibiotic delivery in Staphylococcus aureus biofilms
Authors: Da Costa David , Exbrayat-Héritier Chloé , Rambaud Basile , Megy Simon , Terreux Raphaël , Verrier Bernard , Primard Charlotte
Published: January 2021

Background

After the golden age of antibiotic discovery, bacterial infections still represent a major challenge for public health worldwide. The biofilm mode of growth is mostly responsible for chronic infections that current therapeutics fail to cure and it is well-established that novel strategies must be investigated. Particulate drug delivery systems are considered as a promising strategy to face issues related to antibiotic treatments in a biofilm context. Particularly, poly-lactic acid (PLA) nanoparticles present a great interest due to their ability to migrate into biofilms thanks to their submicronic size. However, questions still remain unresolved about their mode of action in biofilms depending on their surface properties. In the current study, we have investigated the impact of their surface charge, firstly on their behavior within a bacterial biofilm, and secondly on the antibiotic delivery and the treatment efficacy.

Results

Rifampicin-loaded PLA nanoparticles were synthetized by nanoprecipitation and characterized. A high and superficial loading of rifampicin, confirmed by an in silico simulation, enabled to deliver effective antibiotic doses with a two-phase release, appropriate for biofilm-associated treatments. These nanoparticles were functionalized with poly-l-lysine, a cationic peptide, by surface coating inducing charge reversal without altering the other physicochemical properties of these particles. Positively charged nanoparticles were able to interact stronger than negative ones with Staphylococcus aureus, under planktonic and biofilm modes of growth, leading to a slowed particle migration in the biofilm thickness and to an improved retention of these cationic particles in biofilms. While rifampicin was totally ineffective in biofilms after washing, the increased retention capacity of poly-l-lysine-coated rifampicin-loaded PLA nanoparticles has been associated with a better antibiotic efficacy than uncoated negatively charged ones.

Conclusions

Correlating the carrier retention capacity in biofilms with the treatment efficacy, positively charged rifampicin-loaded PLA nanoparticles are therefore proposed as an adapted and promising approach to improve antibiotic delivery in S. aureus biofilms.