bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel variants in Krueppel Like Factor 1 that cause Persistence of Fetal Hemoglobin in In(Lu) individuals
Authors: Eernstman Jesse , Veldhuisen Barbera , Ligthart Peter , Lindern Marieke von , Schoot Ellen van der , Akker Emile van den
Published: April 2021

Beta-hemoglobinopathies become prominent after birth due to a switch from γ-globin to the mutated β-globin. Haploinsufficiency for the erythroid specific indispensable transcription factor Krueppel-like factor 1 (KLF1) is associated with high persistence of fetal hemoglobin (HPFH). The In(Lu) phenotype, characterized by low to undetectable Lutheran blood group expression is caused by mutations within KLF1 gene. These KLF1 variants often lead to KLF1 haploinsufficiency. We screened a donor cohort of 55 Lutheran weak or negative donors for KLF1 variants. To discriminate between weak and negative Lutheran expression, a flow cytometry (FCM) assay was developed to detect Lu polymorphisms. The Lu(a-b-) (negative) donor group, showing a significant decreased CD44 (Indian blood group) expression, also showed increased HbF and HbA2 levels, with outliers expressing >5% HbF. KLF1 exons and promoter sequencing revealed variants in 80% of the Lutheran negative donors. Thirteen different variants plus one high frequency SNP (c.304T>C) were identified of which 6 were novel. In primary erythroblasts, knockdown of endogenous KLF1 resulted in decreased CD44, Lu and increased HbF expression, while KLF1 over-expressing cells were comparable to wild type (WT). In line with the pleiotropic effects of KLF1 during erythropoiesis, distinct KLF1 mutants expressed in erythroblasts display different abilities to rescue CD44 and Lu expression and/or to affect fetal (HbF) or adult (HbA) hemoglobin expression.
Selenium and the risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective observational studies and randomized controlled trials
Authors: Sun Hualei , Long Shao Rong , Chen Gaiyun , Wang Yajuan , Liang Rui , Li Wenjie
Published: April 2021

BackgroundThis meta-analysis of prospective observational studies and randomized controlled trials (RCTs) was carried out to explore the association between selenium and the risk of cardiovascular disease (CVD) and all-cause mortality.Methods and Study DesignWe searched the PubMed, EMBASE and Web of Science database for eligible studies which included the relationship between selenium and the outcomes of interest. 25 prospective observational studies and 9 RCTs were included in our meta-analysis.ResultsThe observational studies showed that there was a significant inverse association between serum selenium and the risk of CVD (RR: 0.78; 95% CI: 0.68–0.89), coronary heart disease (CHD) (RR: 0.75; 95% CI: 0.58–0.95) and all-cause mortality (RR: 0.77; 95% CI: 0.71–0.84). We also found a significant inverse association between selenium supplements and the risk of total CVD (RR: 0.78; 95% CI: 0.62–0.98) and all-cause mortality (RR: 0.81; 95% CI: 0.65-1.00) in RCTs studies.ConclusionsOur meta-analysis found a significant inverse association between selenium and CVD, CHD, and all-cause mortality in prospective observational studies and RCTs, which indicate the selenium has protective effect in cardiovascular disease and all-cause mortality.
In-situ Conservation of Traditional Vegetable Diversity in Wa Homegardens in Southwestern Yunnan, China
Authors: Shao Hua , Hill Rosemary , Xue Dayuan , Yang Jingbiao
Published: April 2021

Background: Homegardens are recognized as in-situ conservation sources of germplasm diversity to overcome homogenous germplasm problems in the industrial agriculture system; it is crucial to understand how smallholders manage their homegardens to maintain traditional genetic resources. Wa is a long-dwelling ethnic group living mainly in southwest Yunnan, China. Traditional vegetables in homegardens management are still central to farmers’ livelihoods in Wa villages. We surveyed traditional vegetables in Wa homegardens and analyzed the factors conserving traditional vegetables in the homegardens management. Methods: The methods used in this work included semi-structured interviews, questionnaires, and field surveys. A total of 60 households through purposive sampling in three townships, 6 villages were surveyed. We documented ethnobotanical information on local name, edible methods, edible parts of traditional vegetables maintained in Wa homegardens. Plant species cultivated in Wa homegardens were identified according to Flora of China.Results: Fifty-five traditional vegetable varieties and 36 hybrid vegetable varieties in the homegardens were recorded. Among all the villages, 23 ± 6 (average ± S.D.) traditional vegetable varieties per homegarden and 9 ± 3 (average ± S.D.) introduced vegetable varieties per homegarden were recorded. 78% of households choose to store the local seeds themselves, with a further 9% of households’ seed supplies coming from neighbors and relatives, other 13% of households choose to purchase local seeds in the markets. In 83% of families, the female head holds the main responsibility for decision making for traditional vegetables planted in homegardens; in 10% of families were male head household to take responsibility for decision-making, and a small percentage which is 2% is determined by the elderly. 5% of families will make decisions jointly between both male and female household heads.Conclusions: This study demonstrated that rich traditional germplasm diversity is harbored in the Wa homegardens because of Wa communities’ unique culture and traditional knowledge, which is practiced daily using homegrown food plants. Local vegetable seed saving and sharing systems can help maintain the germplasm diversity in the Wa community’s homegardens. Wa homegardens can be a practical solution to protect the traditional germplasm diversity and maintain a lifestyle with traditional culture.
A Novel Tooth Tip Relief Method for Reducing Micro-Pitting of Spur Gears
Authors: Xu Xiangyang , Liang Yinghua , Zuo Shumiao , Dong Peng , Liu Yanfang , Wang Shuhan , Wang Zhuo
Published: April 2021

Micro-pitting is a common fatigue failure mode of spur gears. To reduce it, this paper proposes a novel tooth tip relief method. Gear meshing simulation is firstly performed considering the actual contact path, showing that there are four Hertz contact stress peaks in the transition areas of the tooth flank. Equations are then developed for the novel tooth tip relief method: one focuses on the smooth transition between the involute profile and the tip relief region, the other on the smooth transition between the tip relief region and the tooth tip. The results of curvature radius and Hertz contact stress show that the proposed novel method can effectively reduce the Hertz contact stress peaks, which indicates this tip relief method could benefit for reducing the micro-pitting. Finally, both wear simulations and bench tests are conducted, verifying the effectiveness of the proposed method for reducing the micro-pitting of spur gears.
Palmitoylethanolamide for Sleep Disturbance. A Double-blind, Randomised, Placebo-controlled Interventional Study
Authors: Rao Amanda , Ebelt Phillippa , Mallard Alistair , Briskey David
Published: April 2021

Background: Sleep is essential for wellbeing, yet sleep disturbance is a common problem linked to a wide range of health conditions. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide proposed to promote better sleep via potential interaction with the endocannabinoid system.Methods: This double-blind, randomized study on 103 adults compared the efficacy and tolerability of 8 weeks of daily supplemented PEA formulation (350 mg Levagen+TM) to a placebo. Sleep quality and quantity were measured using wrist actigraphy, a sleep diary and questionnaires. Results: At week 8, PEA supplementation reduced sleep onset latency, time to feel completely awake and improved cognition on waking. After 8 weeks, both groups improved their sleep quality and quantity scores similarly. There was no difference between groups at baseline or week 8 for sleep quantity or quality as measured from actigraphy or sleep diaries. Conclusion: These findings support PEA as a potential sleeping aid capable of reducing sleep onset time and improving cognition on waking. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12618001339246. Registered 9th August 2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375493&isReview=true
Polyaniline as a Hippocampus-inspired Biomimetic Device for Electrochemical Monitoring of Phosphorylated Tau induced Neurodegenerative Processes
Authors: Hsu Chien-Chih , Wang Yu-Rong , Tripathi Adarsh , Wang Yu-Lin , Chen Jung-Chih
Published: April 2021

Tau protein plays an important role in Alzheimer’s Disease (AD), especially its hyper-phosphorylated state, which is involved in aggregating and triggering entangled nerve fibers, eventually leading to neuronal death. This study investigates whether this hyper-phosphorylated tau can be dephosphorylated by electrochemical techniques. Aiming at the phosphorylation sites only found in AD brain, we utilized human tau (pS214) peptide as the target for this study. With the help of electrochemical quartz crystal microbalance (EQCM) system, we utilized electrochemical methods to trigger interaction between potential charge and tau protein and monitor the whole reaction on the electrode by QCM. The polyaniline membrane was then used as a hippocampus-inspired biomimetic device to observe charge-protein interactions where positive potential attaches phosphorylated tau and negative potential detaches the phosphoryl group. We successfully found out that 0.5 V can induce complete attachment to phosphorylated tau and − 0.3 V can achieve dephosphorylation of tau peptide. Furthermore, to demonstrate dephosphorylation of tau peptide, we performed mass spectrometry to examine the reaction product and prove our hypothesis. To sum up, this device could be a potential novel treatment for tau-related neurodegenerative diseases.
A Comparative Analysis on Risk Communication between International and Chinese Literature from the Perspective of Knowledge Domains Visualization
Authors: Dong Huiling , Wu Qunhong , Pang Yue , Wu Bingyi
Published: April 2021

Background At the end of 2019, the outbreak of coronavirus disease (COVID-19) severely damaged and endangered people’s lives. Risk communication plays an important role in the response to COVID-19 successfully. Therefore, a comprehensive analysis of risk communication research is necessary, which can understand current research hotspots and reveal new trends.Methods In this study, international articles come from Web of science database (3983), Chinese articles come from the China National Knowledge Infrastructure database (1134), Bibliometric and mapping knowledge domain analysis were used for cooperation network, co-word co-occurrence network and burst detection analysis.Results The first article in this field was published by western scholars earlier, while the first Chinese article in 2002. Research institutions mainly come from universities. The United States play a key role in this field. Chinese scholars had a closer cooperation network, but there was less cooperation among domestic institutions. Risk perception, public trust, risk management, and risk information dissemination had always been the research hot-spots in this academic direction. Trust, sentiment research, and public risk events were essential directions for future. There are 25 burst words for international articles, while 11 burst words for Chinese articles from 2000–2020.Conclusions In summary, both domestic and international researchers are concerned about risk communication, risk perception, trust, and risk information. International scholars begin to take cares with ecological and technological risks research, radiating many areas of social risk. Compared with international research on risk communication more systematic and comprehensive, Chinese scholars takes SARS as the research background and reviewing foreign knowledge as the research starting point. With purpose of practical and applied research based on a public emergency, the risk-communication research lacks continuity in Chinese academy in the past years.
Organic N-type Electrets for Field-effect Transistors, Photo Memories and Artificial Synapses
Authors: Li Dongfan , Qin Zongze , Lu Wanlong , Ren Yurong , Zhu Yuanwei , Wang Hong , Li Shengtao , Bu Laju , Lu Guanghao
Published: April 2021

Electrets, typically referring to insulator materials with permanently-trapped charges, are widely used for electronic devices, actuators and medical filtering. Here, organic n-type electrets, generated from oxygen-degraded n-type semiconductors, are proposed as photo-induced electrets. The sheet charge densities of such n-type electret films, as high as 7.47 × 1012 cm-2, are used to provide steady built-in electric field to significantly improve the performance of organic field-effect transistors (OFETs). For example, OFETs made of p-type semiconductor 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT), in combination with n-type electret N,N′-Dioctyl-3,4,9,10-perylenedicarboximide (C8-PTCDI), show a hole field-effect mobility 13.3 cm2·V−1·s−1, along with a memory window over 100 V, a memory on/off ratio 106 and a stable retention life time over one month in ambient air. Subsequently, the generality of n-type electrets for transistors and photo memories applications are demonstrated. Furthermore, OFETs with organic n-type electrets are employed in artificial synapse, and the recognition rate of brain-inspired neuromorphic computing is 65%.
RLIM: Representation Learning Method for Influence Maximization in social networks
Authors: Chengai Sun , Xiuliang Duan , Liqing Qiu , Qiang Shi , Tengteng Li
Published: April 2021

A core issue in influence propagation is influence maximization, which aims to find a group of nodes under a specific information diffusion model and maximize the final influence of this group of nodes. The limitation of the existing researches is that they excessively depend on the information diffusion model and randomly set the propagation ability (probability). Therefore, most of the algorithms for solving the influence maximization problem are basically difficult to expand in large social networks. Another challenge is that fewer researchers have paid attention to the problem of the large difference between the estimated influence spread and the actual influence spread. A measure to solve the influence maximization problem is applying advanced neural network architecture also represents learning method. Based on this idea, the paper proposes Representation Learning for Influence Maximization (RLIM) algorithm. The premise of this algorithm is to construct the influence cascade of each source node. The key is to adopt neural network architecture to realize the prediction of propagation ability. The purpose is to apply the propagation ability to the influence maximization problem by representation learning. Furthermore, the results of the experiments show that RLIM algorithm has greater diffusion ability than the state-of-the-art algorithms on different online social network data sets, and the diffusion of information is more accurate.
Metformin Resistant MDA-MB-468 Cells Exhibit EMT-like Phenotype and Increased Migration Capacity
Authors: Koker Sahika Cingir , Yalcin Banu , Turacli Irem Dogan
Published: April 2021

Background: Metformin is one of the most prescribed drug for the treatment of type II diabetes. Its anti-proliferative effect is also taken advantage for the treatment of cancer. Despite many of the studies mention the positive effects of metformin in inhibiting the proliferation of cancer cells, there are also studies which questions this idea as well.Methods: In this study, we investigated the most widely studied breast cancer cell lines, ER(+) MCF7 cells, TNBC MDA-MB-231 and MDA-MB468 cells in terms of metastatic behavior under long-term metformin treatment. MCF7, MDA-MB231 and MDA-MB468 cells were gained resistant to metformin starting from 0.2mM to 3.2mM. Results: Compared to MCF7 and MDA-MB231 cell lines, we only observed dramatic changes in MDA-MB468 cells whose morphology has been changed towards mesenchymal like phenotype. Moreoever, migration capacity of these cells were also significanlty increased which were validated at both mRNA and protein levels as well as wound healing assay. In addition EMT like phenotype and increasing migration capacity of metformin resistant MDA-MB468 cells, they exhibited less sensitivity to PI3K inhibitor. Conclusions: All together, our data pointed out that, metformin’s effects should be questioned depending on the subtype of the breast cancer that’s to be treated.
Polyphenol-Rich Muscadine Grape Extract Reduces Triple Negative Breast Cancer Metastasis in Mice with Changes in the Gut Microbiome
Authors: Collard Marianne , Austin Nataleigh N , Brown-Harding Heather , Westwood Brian , Tallant E Ann , Gallagher Patricia E
Published: April 2021

Background

Triple negative breast cancer (TNBC) has a high propensity to metastasize and no treatments are available to slow or prevent metastatic progression. The goal of this study is to determine whether a proprietary high-polyphenol content muscadine grape extract (MGE) inhibits TNBC metastasis.

Methods

4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control (n=8) or treatment group that received 0.1 mg/mL total phenolics MGE in the drinking water (n=8) for 4 weeks. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids (SCFAs) were detected by gas chromatography. MDA-MB-231, BT-549 and 4T1 TNBC cell motility and cytoskeletal organization was assessed in vitr o by scratch wound migration and confocal microscopy, respectively. Data were evaluated by student’s t -test.

Results

MGE reduced metastatic proliferation in mouse lungs (33.3%) and livers (58.3%) and decreased the number (51.1%) and size (17.4%) of liver metastases, resulting in a 55.7% reduction in metastatic tumor burden ( P < 0.01). Serum IL-6 was reduced 99.6% in MGE-treated mice ( P = 0.06). MGE attenuated migration, altered cytoskeletal organization, and reduced RHAMM expression in TNBC cells ( P < 0.05). The gut microbiota, a mediator of polyphenolic bioactivities, was altered significantly in MGE-treated mice; MGE increased the alpha diversity (7.14%), Firmicutes/Bacteroidetes ratio (2-fold), relative abundance of butyrate-producing genera, and butyrate (3-fold) ( P < 0.05). Butyrate inhibited 4T1 cell proliferation and migration, suggesting butyrate contributes to MGE’s anti-metastatic activities ( P < 0.05).

Conclusion

Our results indicate that MGE may be an effective adjuvant therapy to reduce TNBC metastatic progression.
A Novel Blood-Based Assay for Treatment Monitoring of Tuberculosis
Authors: Zimmer Alexandra Jaye , Schumacher Samuel G , Södersten Erik , Mantsoki Anna , Wyss Romain , Persing David H , Banderby Sara , Meuzelaar Linda Strömqvist , Prieto Jacqueline , Gnanashanmugam Devasena , Khatri Purvesh , Ongarello Stefano , Ruhwald Morten , Denkinger Claudia Maria
Published: April 2021

ObjectivesA novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) that has been validated for TB diagnosis. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instruments. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature with time following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment. ResultsOur results show that the 3-gene signature expression level (TB score) changes significantly over time with respect to baseline levels. The greatest increase in TB score occurred within the first month of treatment (median fold-increase in TB score: 1.08 [IQR 0.54-1.52]) and plateaued after 4 months of treatment (median TB score: 1.97 [IQR: 1.03-2.33]. The rapid and substantial increase of the TB score in the first month of treatment holds promise for the early identification of patients that respond to TB treatment. The plateau in TB score at 4 months may indicate early clearance of disease and could direct treatment to be shortened. These hypotheses need to be further explored with large prospective treatment monitoring and test of cure studies.
The Transcription Factor Complex LMO2/TAL1 Regulates Branching and Endothelial Cell Migration in Sprouting Angiogenesis
Authors: Yamada Yoshihiro , Zhong Yi , Miki Shiho , Taura Akiko , Rabbitts Terence
Published: April 2021

The transcription factor complex, consisting of LMO2, TAL1/LYL1, and GATA2, plays an important role in capillary sprouting by regulating VEGFR2, DLL4, and angiopoietin 2 in tip cells. Overexpression of the basic helix-loophelix transcription factor LYL1 in transgenic mice results in shortened tails. This phenotype is associated with vessel hyperbranching and a relative paucity of straight vessels due to DLL4 downregulation in tip cells by forming aberrant complex consisting of LMO2 and LYL1. Knockdown of LMO2 or TAL1 inhibits capillary sprouting in spheroid-based angiogenesis assays, which is associated with decreased angiopoietin 2 secretion. In the same assay using mixed TAL1- and LYL1-expressing endothelial cells, TAL1 was found to be primarily located in tip cells, while LYL1-expressing cells tended to occupy the stalk position in sprouts by upregulating VEGFR1 than TAL1. Thus, the interaction between LMO2 and TAL1 in tip cells plays a key role in angiogenic switch of sprouting angiogenesis.
Visual and proprioceptive feedback mechanisms of precision manual motor control in autism spectrum disorder
Authors: Shafer Robin L , Wang Zheng , Bartolotti James , Mosconi Matthew W.
Published: April 2021

Background

Individuals with Autism Spectrum Disorder (ASD) show deficits processing sensory feedback to reactively adjust ongoing motor behaviors. Atypical reliance on visual and proprioceptive feedback each have been reported during motor behaviors in ASD suggesting that impairments are not specific to one sensory domain but may instead reflect a deficit in multisensory processing, resulting in reliance on unimodal feedback. The present study tested this hypothesis by examining motor behavior across different visual and proprioceptive feedback conditions during a visually guided precision grip force test.
Methods

Participants with ASD (N = 43) and age-matched typically developing (TD) controls (N = 23), range 10–20 years, completed a test of precision gripping. They pressed on force sensors with their index finger and thumb while receiving visual feedback on a computer screen in the form of a horizontal bar that moved upwards with increased force. They were instructed to press so that the bar reached the level of a static target bar and then to hold their grip force as steadily as possible. Visual feedback was manipulated by changing the gain of the force bar. Proprioceptive feedback was manipulated by applying 80 Hz tendon vibration at the wrist to induce an illusion of muscle elongation. Force variability (standard deviation) and irregularity (sample entropy) were examined using multilevel linear models.
Results

While TD controls showed increased force variability with the tendon vibration on compared to off, individuals with ASD showed similar levels of force variability across tendon vibration conditions. Individuals with ASD showed stronger age-associated reductions in force variability relative to controls across conditions. The ASD group also showed greater age-associated increases in force irregularity relative to controls, especially at higher gain levels and when the tendon vibrator was turned on.
Conclusions

Our findings that individuals with ASD show similar levels of force variability and regularity during induced proprioceptive illusions suggest a reduced ability to integrate proprioceptive feedback information to guide ongoing precision manual motor behavior. We also document stronger age-associated gains in force control in ASD relative to TD suggesting delayed development of multisensory feedback control of motor behavior.
Effect of unifaceted and multifaceted interventions on antibiotic prescription control for respiratory diseases: a systematic review of randomised controlled trials
Authors: Chang Yue , Cui Zhezhe , Yang Guanghong , He Xun , Wang Lei , Zhang Xin , Tang Lei
Published: April 2021

Background

The global health system is improperly using antibiotics, particularly in the treatment of respiratory diseases. We aimed to examine the effectiveness of implementing a unifaceted and multifaceted intervention for unreasonable antibiotic prescriptions.
Methods

Relevant literature published in the databases of Pubmed, Embase, Science Direct, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Journal Full-text (CNKI) and Wanfang was searched. Data were independently filtered and extracted by two reviewers based on a pre-designed inclusion and exclusion criteria. The Cochrane collaborative bias risk tool was used to evaluate the quality of the included randomised controlled trials studies.
Results

A total of 1,074 studies were obtained of which 58 were included in the systematic review. Fifty-one studies reported positive results, that is, the primary results in the intervention groups were superior to those in the control groups. The remaining 7 studies had negative or partially negative results. In 19 studies the outcome variable was the antibiotic prescription rate with detailed reports of the number of prescriptions being further analyzed, of which 17 involved educational interventions for doctors, including: (1) Online training using email, web pages and webinar, (2) Antibiotic guidelines for information dissemination measures by email, postal or telephone reminder, (3) Training doctors in communication skills, (4) Short-term interactive educational seminars, and (5) Short-term field training sessions. Seventeen studies of interventions for health care workers also included: (6) Regular or irregular assessment/audit of antibiotic prescriptions, (7) Prescription recommendations from experts and peers delivered at a meeting or online, (8) Publicly reporting on doctors' antibiotic usage to patients, hospital administrators, and health authorities, (9) Monitoring/feedback prescribing behavior to general practices by email or poster, and (10) Studies involving patients and their families (n = 9). Seventeen randomised controlled trials were rated as having a low risk of bias while 2 randomised controlled trials were rated as having a high risk of bias.
Conclusion

The combination of education, prescription audit, prescription recommendations from experts, public reporting, prescription feedback and patient or family member multifaceted interventions can effectively reduce antibiotic prescription rates in health care institutions. Moreover, adding multifaceted interventions to educational interventions can control antibiotic prescription rates and may be a more reasonable method.
Registrations:

This systematic review was registered in PROSPERO, registration number: CRD42020192560.
Freestyle Aortic Root Prosthesis in Combination with Aortic Replacement and Open Anastomosis: A Retrospective Analysis.
Authors: Zientara Alicja , Rosselet-Droux Kim , Bruijnen Hans , Odavic Dragan , Genoni Michele , Dzemali Omer
Published: April 2021

Background: The Freestyle® bioprosthesis is used for pathologies of the aortic root. Additional resection of the ascending aorta and the proximal arch in dissections or aneurysms might be indicated. The aim was to assess mid-term outcome regarding prosthetic performance, stroke, reoperations, and survival in various pathologies comparing patients with and without additional procedures on the ascending aorta and proximal arch focusing on the standardized technique of unilateral antegrade cerebral perfusion under moderate hypothermia. Methods: Retrospective data analysis of 278 consecutive patients after Freestyle® root replacement between September 2007 and March 2017. Patients were divided in three categories due to the pathology of the aortic root (re-operation vs endocarditis vs dissection). Two groups based on the aortic anastomosis technique (non-open arch anastomosis (non-OA) versus open arch anastomosis (OA)) were compared (119 OA vs 159 non-OA). Cardiovascular risk, previous cardiac events, intra- and postoperative data were evaluated. Inferential statistics were performed with Mann-Whitney U-test. Nominal and categorical variables were tested with Fisher-Freeman-Halton exact test. Kaplan-Meier estimate was used to assess survival.Results: The follow-up rate was 90% (median follow-up: 39.5 months). There were differences in the indication (endocarditis: OA 5 (4.2%) vs non-OA 36 (24%), p<0.0001; dissection: OA 13 (10.9%) vs non-OA 2 (1.3%); p=0.0007). OA patients had less perioperative stroke (1 (1%) vs 15 (10%), p=0.001) and shorter hospital stay (9 vs 12 days, p=0.0004). There were no differences in the mortality (in-hospital: non-OA 8 (5%) vs OA 8 (7%); p=0.6; death at follow-up: non-OA 15 (11%) vs OA 5 (5%); p=0.1). Overall valve performance showed a well-functioning valve in 97.3% at follow-up.Conclusion: The valve performance showed excellent results regardless of the initial indication. The incidence of stroke was lower in patients receiving an open arch anastomosis using unilateral antegrade cerebral perfusion without elevated mortality or prolonged hospital stay.
Implementing YouthCHAT – Evaluation and Development of An Implementation Framework
Authors: Martel Rhiannon , Darragh Margot , Goodyear-Smith Felicity
Published: April 2021

Background Northland, New Zealand has a generally socioeconomically deprived population with a high proportion of indigenous Māori. Māori youth suffer a high rate of mental ill-health, substance misuse, and other risky behaviours. While evidence demonstrates that early detection and management of these issues leads to long-term positive health outcomes, implementation of systematic screening and intervention is challenging. This study aimed to implement YouthCHAT, a self-administered digital tool screening young people for mental health concerns and risky health behaviours, into youth services in Northland using an iterative process of implementation, evaluation, and modification, and to create a framework for national-level rollout and implementation.Methods Normalisation Process Theory and a Māori research approach informed the implementation and its evaluation. Data sources included end-user focus groups, staff surveys, field notes, and informal communications with key stakeholders. Number of YouthCHAT screens completed measured intervention uptake.Results: Ongoing staff and youth feedback led to changes in YouthCHAT which increased acceptability. Facilitating two-way communication between providers and management, providing accessible training, and improved e-health record integration assisted uptake. Contextual factors, such as establishing a bicultural co-design approach and programming remote functionality during COVID-19 lockdown, were important factors in YouthCHAT’s ultimate acceptability and implementation. Other impediments such as staff redeployed during meningococcal and measles epidemics merely required patience. An implementation framework for YouthCHAT was developed which addresses tool acceptance and uptake, requiring ongoing effective communication and coordination, and iterative evaluation.Conclusions Failure to launch may be due to the interplay between the intervention, its users, contextual factors, and wider organisational aspects. Interventions may need to be tailored to a specific context to meet the needs of users, and address organisational and system barriers. Ultimately there will only be uptake where providers see this as worthwhile. Perception that its effective use will reduce their workload serves as a valuable incentive. The participatory research and bicultural Māori approaches employed in this project eventually led to YouthCHAT’s successful implementation in Northland. Full ownership of the Northland YouthCHAT version was transferred to local stakeholders on project completion. An iterative and evaluative strategy is recommended for future implementation. While derived for a specific population, the principles are generic, and our framework should be generalisable to other settings.Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12618000299202p, 16-02-2018; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374532
Virtual screening of the potential hCA XII inhibitors based on the pharmacophore modelling, molecular docking, MMGBSA and molecular dynamics simulations studies
Authors: Al-Sanea Mohammad M. , Chilingaryan Garri , Abelyan Narek , Arakelov Grigor , Sahakyan Harutyun , Arakelov Vahram , Hussein Shaimaa , Alazmi Gharam M. , Alsharari Haifa E. , Al-faraj Waad M. , Alruwaili Faten S. , Albilasi Nouf Q. , Alsharari Tahani S. , Alsaleh Abdulaziz A. S. , Alazmi Turki M. , Almalki Atiah H. , Alotaibi Nasser H. , Abdelgawad Mohamed A.
Published: April 2021

Human carbonic anhydrase XII (hCA XII) has gained therapeutic value in the field of medicinal chemistry as a pharmacological target and biomarker for different types of cancer. Despite the fact that interaction features of hCAs inhibitors with the catalytic site of the enzyme are well described, lack in the selectivity of the traditional hCA inhibitors is an urgent issue. This study was devoted to the identification of novel potential hCA XII inhibitors using comprehensive set of computational approaches, including generation of structure-and ligand-based pharmacophore models, molecular docking, MMGBSA calculations and molecular dynamics simulations. As the results of the study multiple potential hCA inhibitors were identified. Along with the identified derivatives of the classical hCA inhibitors (have sulfonamide motifs), several compounds with alternative chemical scaffolds, that can be considered and further investigated as potential non-classical hCA XII inhibitors, were identified.
The relations between different factors of intolerance of uncertainty and symptoms of generalized anxiety disorder: a network analysis
Authors: Ren Lei , Wei Zihan , Li Ye , Cui Long-Biao , Wang Yifei , Wu Lin , Wei Xinyi , Peng Jiaxi , Li Kuiliang , Jin Yinchuan , Li Fengzhan , Yang Qun , Liu Xufeng
Published: April 2021

Background: Intolerance of uncertainty (IU) is considered as a specific risk factor in the development and maintenance of generalized anxiety disorder (GAD). Yet, researches have investigated the relations between IU and GAD (or worry) using total scores on self-report measures. This ignores that there are two different factors exist in IU, and clinical heterogeneity and differential relations among symptoms of GAD. In the present study, we explored the relations among different factors of IU and symptoms of GAD.Methods: A dimensional approach which take individual differences into consideration in different factors of IU along a full range of normal to abnormal symptom severity levels of GAD were used in this study. Unregularized partial-correlation networks were estimated using cross-sectional data from 624 university students. Factors of IU were measured by 12-item Intolerance of Uncertainty Scale and symptoms of GAD were measured by Generalized Anxiety Disorder 7-Item Questionnaire. Results: Five edges between two factors of IU and symptoms of GAD, including edges are between “prospective anxiety” and “nervousness or anxiety”, between “prospective anxiety” and “worry too much”, between “inhibitory anxiety” and “uncontrollable worry”, between “inhibitory anxiety” and “worry too much”, and between “inhibitory anxiety” and “restlessness”. The symptom “worry too much” had the highest strength centrality in the present network. In the community of IU, factor “inhibitory anxiety” has the higher bridge strength than factor “prospective anxiety”. And in the community of GAD symptoms, symptom “worry too much” has the higher bridge strength than other symptoms.Conclusions: This study reveals the underlying relationship between factors of IU and various symptoms of GAD. These findings may provide some references for related preventions and interventions, such as targeting “worry too much” may minimize the level of both IU and GAD symptoms and focusing on “inhibitory anxiety” may be more effective at reducing symptoms of GAD than focusing on “prospective anxiety”.
Ophthalmic pathologies in an older HIV-positive Tanzanian population and their association with neurological morbidity and evaluation of a low-resource screening strategy
Authors: George Grace , Murphy Declan C , Hogg HD Jeffry , Boniface Japhet Bright , Urasa Sarah , Rwiza Justus , Uwemeye Livin , Bristow Clare , Hillsmith Grace , Rainey Emma , Walker Richard , Gray William K , Maria-Paddick Stella
Published: April 2021

Background

Globally, 43 million people are living with HIV, 90% in developing countries. Increasing life expectancy with combination antiretroviral therapy (cART) results in chronic complications, including HIV-associated neurocognitive disorders (HAND) and eye diseases. HAND screening is currently challenging.
Objectives

To evaluate clinical utility of HIV-retinopathy as a screening measure of HAND in older cART-treated individuals in Tanzania and feasibility of smartphone-based retinal screening in this low-resource setting.
Methods

A cross-sectional systematic sample aged ≥ 50-years attending routine HIV follow-up in Tanzania were comprehensively assessed for HAND by American Academy of Neurology criteria and received ophthalmic assessment including smartphone-based retinal imaging. HAND and ophthalmic assessments were independent and blinded. Diagnostic accuracy was evaluated by AUROC curves.
Results

Of 129 individuals assessed, 69.8% were visually impairment. Six had suspected HIV retinopathy. HAND prevalence was 66.7%. HIV retinopathy was significantly associated with HAND but HIV-disease factors (CD4, viral load) were not. Diagnostic accuracy of HIV-retinopathy for HAND was poor (AUROC 0.545–0.617) but specificity and positive predictive value were high.
Conclusions

Ocular pathology and HAND appear highly prevalent in this low-resource setting. Although retinal screening cannot be used alone identify HAND, prioritization of individuals with abnormal retinal screening is a potential strategy in low-resource settings.
Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants
Authors: Ikegame Satoshi , Siddiquey Mohammed , Hung Chuan-Tien , Haas Griffin , Brambilla Luca , Oguntuyo Kasopefoluwa , Kowdle Sheryas , Vilardo Ariel , Edelstein Alexis , Perandones Claudia , Kamil Jeremy , Lee Benhur
Published: April 2021

The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China1,2. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales have prompted re-evaluation of strategies to achieve universal vaccination3. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic4–8. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that only 1 out of 12 serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.
Are Antibiotics Prescribed to Inpatients According to Recommended Standard Guidelines in Juba Teaching Hospital, South Sudan? A Retrospective Cross-sectional Study
Authors: Otim Michael Ekubu , Demaya Desmond Kabuya , Al-Marzouqi Amina M , Mukasa Jean P.
Published: April 2021

Background: The emergence and spread of antibiotic resistance occurred at an alarming rate globally, and has limited the use of antibiotics for preventing and treating infectious diseases. Failure to follow guidelines and protocols for antibiotic use for rational therapeutics and infection control has led to overuse and misuse of antibiotics. However, there is paucity of data on the current pattern of antibiotics prescribing for hospitalised patients in South Sudan, which is among the youngest countries in the world. Therefore, this study aimed to explore the prescription and use of antibiotics at Juba Teaching Hospital (JTH) in South Sudan.Methods:A retrospective cross-sectional study was conducted among JTH inpatients between January and December 2016. A sample of 316 files from the medical and surgical wards were extracted using probability sampling proportional to ward size. Extracted files were reviewed to determine the pattern of antibiotics administration. Data on indications for antibiotic use were also collected. All data were entered twice and analysed using STATA version 13.0.Results: In all reviewed files, patients received treatment with antibiotics. Antibiotic use was highest in the medical ward (75.4%). Conditions in which antibiotic use was most prevalent were infectious and parasitic diseases (23.7%) and diseases of the digestive system (19.9%). The top three antibiotics prescribed were ceftriaxone (21.2%), metronidazole (20.0%) and amoxicillin (11.5%). The majority of patients (40.2%) were treated with two antibiotics. Conclusions: This study revealed a high level of inappropriate antibiotics use at JJTH. Furthermore, there is non-adherence to national/international guidelines in administration of these antibiotics among doctors. It is necessary to introduce antibiotic stewardship activity, along with continuous national surveillance and enforcement to reduce irrational antibiotics use and the associated risk for antibiotic resistance.
Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): a stepped wedge cluster randomised trial within the EFFECTS trial
Authors: Isaksson Eva , Näsman Per , Wester Per , Laska Ann-Charlotte , Lundström Erik
Published: April 2021

Background: Two out of three randomised controlled trials fail to meet their recruitment goals. Recruitment to EFFECTS, a trial of fluoxetine for stroke recovery was slower than anticipated. We aimed to evaluate an intervention to improve recruitment to EFFECTS.Methods: We performed a stepped wedge, cluster randomised trial embedded in the ongoing EFFECTS trial. The Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC) comprised a structured teleconference with the study personnel and the head of department supplemented by a commitment contract. ERUTECC’s primary outcome was the number of patients recruited into EFFECTS per 60 days per site. We compared the recruitment 60 days before the intervention with 60 days after and considered at least a 20% increase to be a positive outcome. All centres started as controls and were followed by 60 days observation. The order in which the centres began was decided through block randomisation.Results: At randomisation, EFFECTS had 29 active centres. ERUTECC recruited 20 centres between 9th Nov 2017 and 30th June 2018, providing 80 site months of observation for the primary analysis.The inclusion rate was 1.9 patient/centre/60 days before the intervention and 2.1 patient/centre/60 days after the intervention, representing a 10% overall increase. However, the recruitment increased more than 20% the first 30 days after the intervention. We also noted that inclusion rate increased directly after the first contact with the centres, announcing a future telephone conference. Some centres changed their screening process, transferring the task from doctors to nurses.Conclusions: Although a teleconference with the study personnel and the head of department accompanied by a commitment contract did not increase recruitment to an RCT by more than 20%, 60 days post intervention, recruitment improved during the first month, especially at low-recruitment centres.Trial registration : The ERUTECC study was registered in the Northern Ireland Hub for Trials Methodology Research Studies Within a Trial Repository (SWAT58) 30 April 2017. https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/SWATSWARInformation/Repositories/SWATStore/EFFECTS was retrospectively registered 2 February 2016 in ClinicalTrials.gov: NCT02683213.
Nanosilver toxicity thresholds estimative for aquatic and sediment environmental safety
Authors: Castro Vera Lucia , Jonsson Claudio , Silva Mariana Silveira Guerra M. , Castanha Rodrigo , Vallim Jose Henrique , Silva Leticia da , Oliveira Raissa de , Correa Daniel , Ferreira Marcos David
Published: April 2021

Silver nanoparticles (AgNPs) have been largely utilized. Despite that, comprehensive studies on their ecotoxicological effects and environmental risk are still required. In the present study, the AgNPs effect was assessed to some organisms including algae, plants, microcrustaceans, cnidaria, nematodes, aquatic insect, earthworm, and fish embryos. The no-observed-effect concentration (NOEC) was calculated for each organism using a log-logistic function. AgNPs remained stable in contact with culture media during the analyzed period and conditions employed, presenting dispersion less than 20%, except for Artemia salina medium. On this occasion, NPs presented dispersion of approximately 25%, although their size remained unchangeable. The Predicted No Effect Concentration (PNEC) of AgNPs in the aquatic compartment was estimated in the concentration range from 0.13 to 0.66 µg L-1. A Risk Quotient (RQ) of 15.1 was derived for the NP tested with the aid of a maximum AgNPs Predicted Environmental Concentration (PEC) estimated value. The RQ value superior to one indicates a risk and the need for its management measures implementation. These data, in addition to the expected increase in AgNPs use, reinforce the importance of the AgNPs safety levels establishment that can contribute to performing their risk assessment studies.
Schwannoma of the posterior pharyngeal wall in a child
Authors: Zhu Peng , Li Xiao Yan
Published: April 2021

Background: To our knowledge, There are only 7 cases of posterior pharyngeal wall schwannoma which have been previously reported in the literature, but none of them was associated with a 3-year-old child.Case presentation: We presented a rare case of a schwannoma which is localized on the posterior pharyngeal wall, It caused severe difficulty in swallowing and breathing in a child whose age is three years old. Schwannomas of the posterior pharyngeal wall has been rarely reported in children, The tumor was removed with plasma radio frequency excision via a transoral route, There was not seen any recurrence of tumor by examination of CT or MRI up to two years. as far as we know, It's the first time which a case of posterior pharyngeal wall schwannoma that has been reported to occur in a 3-year-old child, and the first case in which the schwannoma was removed via transoral plasma radio frequency excision.Conclusions: This case illustrates that schwannoma may be found in children ,and it is safe to treat this disease through plasma radio frequency excision via a transoral route.