bluuebunny/crossref_metadata_2025 huggingface dataset:
The stability of outcomes of cancellous autografts with acellular membrane for extended osteochondritis of the knee. Outcomes for 22 AMIC® grafts at an average follow-up of 4 years
Authors: Pauvert Adrien , Chainard Caroline Vincelot , Buisson Xavier , Robert Henri
Published: February 2021

Objectives:

Loss of osteochondral substances resulting from osteochondritis dissecans (OCD) of the knee are arthrogenic in the long term. When they exceed 2 cm2, the Autologous Matrix Induced Chondrogenesis (AMIC®) technique is one of the methods used in France. The objective of this study was to evaluate the medium-term results of the AMIC® technique.

Methods:

This was a consecutive, prospective, single-center, single-operator series of 22 patients (13 men, 9 women, mean age 28 years (15-51)) treated by AMIC® (spongy bone graft + sutured collagen membrane) between September 2011 and November 2016. Previous surgery had been performed on 17 patients. According to the ICRS classification, the lesion was stage IV in 21 cases and stage III in 1 case. The sites were: condylar: 19 cases, patellar: 2 cases and trochlear: 1 case. The mean surface area was 3.6 cm2 (2-8) and the depth was 0.5 mm (0.4-0.8). All the patients were functionally assessed by an independent examiner using validated functional scores for these indications (KOOS, subjective IKDC). Student’s T tests were used.

Results:

At a mean follow-up of 4 years (minimum 2 years) all but 2 patients had significantly improved (In preop. IKDC: 44±14 and KOOS: 56±17). In these 2 cases, the postoperative scores remained unchanged over the years: one patient had had several surgeries before the graft and a 51-year-old female patient had an extensive lesion of 6.9 cm2. The mean IKDC and KOOS scores were 73±18 and 78±15 and then 77±16 and 81±14 respectively, at 1 and 4 years (p> 0.05 for IKDC and KOOS). Regrettably there were 2 complications: 1 arthrolysis 1 year after surgery and 1 algodystrophy.

Conclusion:

Few techniques are available in France for extensive symptomatic osteochondral lesions. AMIC® is a reliable, one-step, reproducible, inexpensive technique for loss of substance due to OCD with stable results as of 1 year after surgery.
Knowledge-Behavior Gap on COVID-19 among Older People in Rural Thailand
Authors: Vicerra Paolo Miguel Manalang
Published: February 2021

This study analyzed the difference between rural and urban older adults in Thailand regarding the relationship between the knowledge and behavior toward the prevention of contracting COVID-19. Path analysis was used to observe if the performance of protective behaviors was affected by the level of knowledge that older people have about the disease. This study used the Impact of COVID-19 on Older Persons in Thailand survey collected across the five regions of the country.

Rural residents benefited from community network of village health volunteers who provided information during the pandemic but, they had disadvantages on accessing newer media sources, mainly the internet, for the latest developments on COVID-19. Rural older adults had a higher level of knowledge about COVID-19 than those in urban areas; no difference was observed regarding their behavior to prevent themselves from being infected. The knowledge-behavior gap was viewed as a mechanism of cognitive avoidance because of overwhelming unprecedented information.
Impact of COVID-19 on the Knowledge and Attitudes of Dentists toward Teledentistry
Authors: Plaza-Ruíz S.P. , Barbosa-Liz D.M. , Agudelo-Suárez A.A.
Published: February 2021

Introduction:

The coronavirus disease 2019 (COVID-19) pandemic has created a new scenario for dental practice, and teledentistry (TD) is a field of relevance for dentists.

Objective:

To evaluate the impact of the COVID-19 pandemic on the knowledge, practices, and expectations of dentists toward TD and its association with sociodemographic variables.

Methods:

A cross-sectional survey was administered to dentists in Colombia as part of global research on the impact of COVID-19 on dentistry. The core questionnaire included 5 additional questions on TD that were added by the Colombian research team in 5 domains about TD: Q1, knowledge; Q2, practices; Q3, expectations; Q4, usefulness; and Q5, reimbursement. Sociodemographic variables were also measured. The questionnaire was validated in a pilot test and administered via digital media. Descriptive and bivariate analysis for sociodemographic and TD variables were done. For the evaluation of the chances of a determined answer, an ordinal multinomial logistic regression (Q1 and Q2) and binomial logistic regression (Q3 and Q5) analyses were made.

Results:

In total, 5,370 dentists answered the survey (women: 3,878; mean age: 45 y). The response rate of the survey was 16.84%. Knowledge and practice of TD before the COVID-19 pandemic were both low (25.75% and 12.42%, respectively); however, since the beginning of the current pandemic, knowledge increased by 62.72% and practice by 42.53%. Some 93.1% of respondents considered that TD could be useful in their clinical practice, and 59.55% would consider practicing it after the pandemic. A high number of dentists (88.58%) did not charge for these services. Logistic regressions showed significant differences according to sociodemographic variables.

Conclusions:

The COVID-19 pandemic has had a great impact on TD, increasing knowledge and practice significantly. Dentists expect to continue practicing TD in the future. However, some geographical, technological, and attitudinal barriers need to be broken down to increase daily use of TD.

Knowledge Transfer Statement:

This article provides an overview about the impact of COVID-19 pandemic in the knowledge and attitudes about teledentistry (TD) in general dentists and both clinical and nonclinical specialists. Although some barriers to the use of TD continue, this pandemic brought with it a new scenario for dental practice, which must be implemented through training for professionals to increase its use.
Planning for tourist urban evacuation routes: A framework for improving the data collection and evacuation processes
Authors: Wachtel Guy , Schmöcker Jan-Dirk , Hadas Yuval , Gao Yuhan , Nahum Oren E , Ben-Moshe Boaz
Published: February 2021

Tourism is one of the largest growing industries worldwide. As the number of tourists is rapidly increasing, so too are tourist safety concerns. The increasing frequency of natural disasters along with the growth of urban areas makes it even more complex to address the resilience of tourists during such events. This article proposes a framework for collecting information about tourist locations and flows within urban areas and how to use this information for more efficient and safe evacuation routing. We define population behavior models that can be obtained from gathering empirical data and categorize them into three groups. We review the different evacuation scenarios (divided into sudden and predictable scenarios) and the types of information needed in each case. Further, we discuss the complexity of monitoring and forecasting tourists’ movements in the long term and for short-term predictions including the available data sources for doing so. The data gathering and tourist behavior are explained with examples from Kyoto, Japan, a major tourist attraction and a location that is prone to disasters. Finally, technological solutions for better guidance during the evacuation process of the population are discussed, including low-tech ones and advanced options such as websites, apps and Bluetooth Low Energy sensors, where the last one is demonstrated by a navigation experiment in a 3D environment.
Modeling regional impacts and resilience to water service disruptions in urban economies
Authors: Pagsuyoin Sheree A , Santos Joost R
Published: February 2021

Water is a critical natural resource that sustains the productivity of many economic sectors, whether directly or indirectly. Climate change alongside rapid growth and development are a threat to water sustainability and regional productivity. In this paper, we develop an extension to the economic input-output model to assess the impact of water supply disruptions to regional economies. The model utilizes the inoperability variable, which measures the extent to which an infrastructure system or economic sector is unable to deliver its intended output. While the inoperability concept has been utilized in previous applications, this paper offers extensions that capture the time-varying nature of inoperability as the sectors recover from a disruptive event, such as drought. The model extension is capable of inserting inoperability adjustments within the drought timeline to capture time-varying likelihoods and severities, as well as the dependencies of various economic sectors on water. The model was applied to case studies of severe drought in two regions: (1) the state of Massachusetts (MA) and (2) the US National Capital Region (NCR). These regions were selected to contrast drought resilience between a mixed urban–rural region (MA) and a highly urban region (NCR). These regions also have comparable overall gross domestic products despite significant differences in the distribution and share of the economic sectors comprising each region. The results of the case studies indicate that in both regions, the utility and real estate sectors suffer the largest economic loss; nonetheless, results also identify region-specific sectors that incur significant losses. For the NCR, three sectors in the top 10 ranking of highest economic losses are government-related, whereas in the MA, four sectors in the top 10 are manufacturing sectors. Furthermore, the accommodation sector has also been included in the NCR case intuitively because of the high concentration of museums and famous landmarks. In contrast, the Wholesale Trade sector was among the sectors with the highest economic losses in the MA case study because of its large geographic size conducive for warehouses used as nodes for large-scale supply chain networks. Future modeling extensions could potentially include analysis of water demand and supply management strategies that can enhance regional resilience against droughts. Other regional case studies can also be pursued in future efforts to analyze various categories of drought severity beyond the case studies featured in this paper.
Financial Wellbeing-The Missing Piece in Holistic Wellbeing
Authors: Jaggar Sneha , Navlakhi Lovaii
Published: February 2021

The top causes of stress for employees, based on various studies, are financial or money matters and their challenges. Organisations recognise the impact this worry creates for the firm at large and thus financial wellbeing programmes are slowly gaining popularity. There is evidence to show how financial wellbeing is an integral part of holistic wellbeing, and organisations are experimenting with methods to disseminate financial literacy. In order to avoid the pitfalls of trying something big and failing, organisations and particularly human resource (HR) should spearhead the initiative of duly customised financial wellness programmes (FWPs) for their employees which address their pains and keep aside a budget for the same. Like any relationship, this too needs time to grow; finding a partner early whose objective aligns with that of the HR in ensuring holistic wellbeing for the employee is the important first step. The recent regulations for Registered Investment Advisors promulgated by SEBI allow HR in organisations to use them as a first filter in selecting their financial wellbeing partner.
Wellness Through Volunteering
Authors: Madhusudan Aarti , Sahai Shalabh
Published: February 2021

Beginning in 2004, long before the CSR Act 1 ushered a new spirit in corporate contribution in social development, iVolunteer has worked with over 100 leading Indian and multinational companies across a range of volunteering types from one-time episodic volunteering to more recently virtual volunteering. Our programmes have the potential to engage a range of employee motivations to volunteer. In this article, we examine the perceived notions about volunteering impact on well-being and if it can make a difference to work life? We share our experience over the years and will examine the impact of volunteering on wellbeing and positive mental health of the volunteers. There are almost no known Indian studies that explore this in detail. Individual companies do report higher satisfaction among employees who volunteer, regarding their work life. The article will draw upon insights from the HR community as well as from those executing volunteering in corporates in addition to some conclusions that we will draw based on some research studies. We hope to provide some possible ways forward for corporates to play a part in greater citizen engagement while creating pathways for mindful volunteering benefitting their employees both from a work and a societal perspective. The aim is to create a strong action plan to increase volunteering to both serve a social purpose and sustain the same by drawing out the positive impact that it can have on the individual.
Correction of β-thalassemia by CRISPR/Cas9 editing of the α-globin locus in human hematopoietic stem cells
Authors: Pavani Giulia , Fabiano Anna , Laurent Marine , Amor Fatima , Cantelli Erika , Chalumeau Anne , Maule Giulia , Tachtsidi Alexandra , Concordet Jean-Paul , Cereseto Anna , Mavilio Fulvio , Ferrari Giuliana , Miccio Annarita , Amendola Mario
Published: February 2021

β-thalassemias (β-thal) are a group of blood disorders caused by mutations in the β-globin gene (HBB) cluster. β-globin associates with α-globin to form adult hemoglobin (HbA, α2β2), the main oxygen-carrier in erythrocytes. When β-globin chains are absent or limiting, free α-globins precipitate and damage cell membranes, causing hemolysis and ineffective erythropoiesis. Clinical data show that severity of β-thal correlates with the number of inherited α-globin genes (HBA1 and HBA2), with α-globin gene deletions having a beneficial effect for patients. Here, we describe a novel strategy to treat β-thal based on genome editing of the α-globin locus in human hematopoietic stem/progenitor cells (HSPCs). Using CRISPR/Cas9, we combined 2 therapeutic approaches: (1) α-globin downregulation, by deleting the HBA2 gene to recreate an α-thalassemia trait, and (2) β-globin expression, by targeted integration of a β-globin transgene downstream the HBA2 promoter. First, we optimized the CRISPR/Cas9 strategy and corrected the pathological phenotype in a cellular model of β-thalassemia (human erythroid progenitor cell [HUDEP-2] β0). Then, we edited healthy donor HSPCs and demonstrated that they maintained long-term repopulation capacity and multipotency in xenotransplanted mice. To assess the clinical potential of this approach, we next edited β-thal HSPCs and achieved correction of α/β globin imbalance in HSPC-derived erythroblasts. As a safer option for clinical translation, we performed editing in HSPCs using Cas9 nickase showing precise editing with no InDels. Overall, we described an innovative CRISPR/Cas9 approach to improve α/β globin imbalance in thalassemic HSPCs, paving the way for novel therapeutic strategies for β-thal.
Comparative chloroplast genomes: insights into the evolution of the chloroplast genome of Camellia sinensis and the phylogeny of Camellia
Authors: Li Li , Hu Yunfei , He Min , Zhang Bo , Wu Wei , Cai Pumo , Huo Da , Hong Yongcong
Published: February 2021

Background

Chloroplast genome resources can provide useful information for the evolution of plant species. Tea plant (Camellia sinensis) is among the most economically valuable member of Camellia. Here, we determined the chloroplast genome of the first natural triploid Chinary type tea (‘Wuyi narcissus’ cultivar of Camellia sinensis var. sinensis, CWN) and conducted the genome comparison with the diploid Chinary type tea (Camellia sinensis var. sinensis, CSS) and two types of diploid Assamica type teas (Camellia sinensis var. assamica: Chinese Assamica type tea, CSA and Indian Assamica type tea, CIA). Further, the evolutionary mechanism of the chloroplast genome of Camellia sinensis and the relationships of Camellia species based on chloroplast genome were discussed.

Results

Comparative analysis showed the evolutionary dynamics of chloroplast genome of Camellia sinensis were the repeats and insertion-deletions (indels), and distribution of the repeats, indels and substitutions were significantly correlated. Chinese tea and Indian tea had significant differences in the structural characteristic and the codon usage of the chloroplast genome. Analysis of sequence characterized amplified region (SCAR) using sequences of the intergenic spacers (trnE/trnT) showed none of 292 different Camellia sinensis cultivars had similar sequence characteristic to triploid CWN, but the other four Camellia species did. Estimations of the divergence time showed that CIA diverged from the common ancestor of two Assamica type teas about 6.2 Mya (CI: 4.4–8.1 Mya). CSS and CSA diverged to each other about 0.8 Mya (CI: 0.4–1.5 Mya). Moreover, phylogenetic clustering was not exactly consistent with the current taxonomy of Camellia.

Conclusions

The repeat-induced and indel-induced mutations were two important dynamics contributed to the diversification of the chloroplast genome in Camellia sinensis, which were not mutually exclusive. Chinese tea and Indian tea might have undergone different selection pressures. Chloroplast transfer occurred during the polyploid evolution in Camellia sinensis. In addition, our results supported the three different domestication origins of Chinary type tea, Chinese Assamica type tea and Indian Assamica type tea. And, the current classification of some Camellia species might need to be further discussed.
Characterization and fine mapping of a new dwarf mutant in Brassica napus
Authors: Li Xin , Xiang Fujiang , Zhang Wei , Yan Jindong , Li Xinmei , Zhong Ming , Yang Piao , Chen Caiyan , Liu Xuanming , Mao Donghai , Zhao Xiaoying
Published: February 2021

Background

Plant height is an important plant characteristic closely related to yield performance of many crops. Reasonable reduction of plant height of crops is beneficial for improving yield and enhancing lodging resistance.

Results

In the present study, we described the Brassica napus dwarf mutant bnd2 that was isolated using ethyl methanesulfonate (EMS) mutagenesis. Compared to wild type (WT), bnd2 exhibited reduced height and shorter hypocotyl and petiole leaves. By crossing the bnd2 mutant with the WT strain, we found that the ratio of the mutant to the WT in the F2 population was close to 1:3, indicating that bnd2 is a recessive mutation of a single locus. Following bulked segregant analysis (BSA) by resequencing, BND2 was found to be located in the 13.77–18.08 Mb interval of chromosome A08, with a length of 4.31 Mb. After fine mapping with single nucleotide polymorphism (SNP) and insertion/deletion (InDel) markers, the gene was narrowed to a 140-Kb interval ranging from 15.62 Mb to 15.76 Mb. According to reference genome annotation, there were 27 genes in the interval, of which BnaA08g20960D had an SNP type variation in the intron between the mutant and its parent, which may be the candidate gene corresponding to BND2. The hybrid line derived from a cross between the mutant bnd2 and the commercial cultivar L329 had similar plant height but higher grain yield compared to the commercial cultivar, suggesting that the allele bnd2 is beneficial for hybrid breeding of lodging resistant and high yield rapeseed.

Conclusion

In this study, we identified a novel dwarf mutant of rapeseed with a new locus, which may be useful for functional analyses of genetic mechanisms of plant architecture and grain yield in rapeseed.
Using a distribution-based approach and systematic review methods to derive minimum clinically important differences
Authors: Watt Jennifer A. , Veroniki Areti Angeliki , Tricco Andrea C. , Straus Sharon E.
Published: February 2021

Background

Clinical interpretation of changes measured on a scale is dependent on knowing the minimum clinically important difference (MCID) for that scale: the threshold above which clinicians, patients, and researchers perceive an outcome difference. Until now, approaches to determining MCIDs were based upon individual studies or surveys of experts. However, the comparison of meta-analytic treatment effects to a MCID derived from a distribution of standard deviations (SDs) associated with all trial-specific outcomes in a meta-analysis could improve our clinical understanding of meta-analytic treatment effects.

Methods

We approximated MCIDs using a distribution-based approach that pooled SDs associated with baseline mean or mean change values for two scales (i.e. Mini-Mental State Exam [MMSE] and Alzheimer Disease Assessment Scale – Cognitive Subscale [ADAS-Cog]), as reported in parallel randomized trials (RCTs) that were included in a systematic review of cognitive enhancing medications for dementia (i.e. cholinesterase inhibitors and memantine). We excluded RCTs that did not report baseline or mean change SD values. We derived MCIDs at 0.4 and 0.5 SDs of the pooled SD and compared our derived MCIDs to previously published MCIDs for the MMSE and ADAS-Cog.

Results

We showed that MCIDs derived from a distribution-based approach approximated published MCIDs for the MMSE and ADAS-Cog. For the MMSE (51 RCTs, 12,449 patients), we derived a MCID of 1.6 at 0.4 SDs and 2 at 0.5 SDs using baseline SDs and we derived a MCID of 1.4 at 0.4 SDs and 1.8 at 0.5 SDs using mean change SDs. For the ADAS-Cog (37 RCTs, 10,006 patients), we derived a MCID of 4 at 0.4 SDs and 5 at 0.5 SDs using baseline SDs and we derived a MCID of 2.6 at 0.4 SDs and 3.2 at 0.5 SDs using mean change SDs.

Conclusion

A distribution-based approach using data included in a systematic review approximated known MCIDs. Our approach performed better when we derived MCIDs from baseline as opposed to mean change SDs. This approach could facilitate clinical interpretation of outcome measures reported in RCTs and systematic reviews of interventions. Future research should focus on the generalizability of this method to other clinical scenarios.
Hepatitis C viraemic and seroprevalence and risk factors for positivity in Northwest Cambodia: a household cross-sectional serosurvey
Authors: Lynch Emily , Falq Gregoire , Sun Chhorvy , Bunchhoeung Pharm D Tek , Huerga Helena , Loarec Anne , Dousset Jean-Phillipe , Marquardt Tonia , Paih Mickael Le , Maman David
Published: February 2021

Background

Despite a dramatic reduction in HCV drug costs and simplified models of care, many countries lack important information on prevalence and risk factors to structure effective HCV services.

Methods

A cross-sectional, multi-stage cluster survey of HCV seroprevalence in adults 18 years and above was conducted, with an oversampling of those 45 years and above. One hundred forty-seven clusters of 25 households were randomly selected in two sets (set 1=24 clusters ≥18; set 2=123 clusters, ≥45). A multi-variable analysis assessed risk factors for sero-positivity among participants ≥45. The study occurred in rural Moung Ruessei Health Operational District, Battambang Province, Western Cambodia.

Results

A total of 5098 individuals and 3616 households participated in the survey. The overall seroprevalence was 2.6% (CI95% 2.3–3.0) for those ≥18 years, 5.1% (CI95% 4.6–5.7) for adults ≥ 45 years, and 0.6% (CI95% 0.3–0.9) for adults 18–44. Viraemic prevalence was 1.9% (CI95% 1.6–2.1), 3.6% (CI95% 3.2–4.0), and 0.5% (CI95% 0.2–0.8), respectively. Men had higher prevalence than women: ≥18 years male seroprevalence was 3.0 (CI95% 2.5–3.5) versus 2.3 (CI95% 1.9–2.7) for women. Knowledge of HCV was poor: 64.7% of all respondents and 57.0% of seropositive participants reported never having heard of HCV.

Risk factor characteristics for the population ≥45 years included: advancing age (p< 0.001), low education (higher than secondary school OR 0.7 [95% CI 0.6–0.8]), any dental or gum treatment (OR 1.6 [95% CI 1.3–1.8]), historical routine medical care (medical injection after 1990 OR 0.7 [95% CI 0.6–0.9]; surgery after 1990 OR 0.7 [95% CI0.5–0.9]), and historical blood donation or transfusion (blood donation after 1980 OR 0.4 [95% CI 0.2–0.8]); blood transfusion after 1990 OR 0.7 [95% CI 0.4–1.1]).

Conclusions

This study provides the first large-scale general adult population prevalence data on HCV infection in Cambodia. The results confirm the link between high prevalence and age ≥45 years, lower socio-economic status and past routine medical interventions (particularly those received before 1990 and 1980). This survey suggests high HCV prevalence in certain populations in Cambodia and can be used to guide national and local HCV policy discussion.
Psychological interventions for maternal depression among women of African and Caribbean origin: a systematic review
Authors: Jidong Dung Ezekiel , Husain Nusrat , Roche Ayesha , Lourie Grace , Ike Tarela J. , Murshed Maisha , Park Miriam S. , Karick Haruna , Dagona Zubairu K. , Pwajok Juliet Y. , Gumber Anil , Francis Christopher , Nyam Pam P. , Mwankon Shadrack B.
Published: February 2021

Background

Maternal depression is a leading cause of disease burden for women worldwide; however, there are ethnic inequalities in access to psychological interventions in high-income countries (HICs). Culturally appropriate interventions might prove beneficial for African and Caribbean women living in HICs as ethnic minorities.

Methods

The review strategy was formulated using the PICo (Population, phenomenon of Interest, and Context) framework with Boolean operators (AND/OR/NOT) to ensure rigour in the use of search terms (“postpartum depression”, “maternal depression”, “postnatal depression”, “perinatal depression” “mental health”, “psychotherapy” “intervention”, “treatment”, “black Caribbean”, “black African”, “mothers” and “women”). Five databases, including Scopus, PsycINFO, Applied Social Science Index and Abstracts (ASSIA), ProQuest Central and Web of Science, were searched for published articles between 2000 and July 2020. 13 studies met the inclusion criteria, and the relevant data extracted were synthesised and thematically analysed.

Results

Data syntheses and analyses of included studies produced four themes, including (1) enhance parenting confidence and self-care; (2) effective mother–child interpersonal relationship; (3) culturally appropriate maternal care; and (4) internet-mediated care for maternal depression.

Conclusion

In the quest to address maternal mental health disparities among mothers of African and Caribbean origin in HICs, the authors recommend culturally adapted psychological interventions to be tested in randomised control trials.
Taohuajing reduces oxidative stress and inflammation in diabetic cardiomyopathy through the sirtuin 1/nucleotide-binding oligomerization domain-like receptor protein 3 pathway
Authors: Yao Rui , Cao Yu , Wang Changming , Xu Lu , Zhang Xuan , Deng Yuqing , Li Feng , Wang Siwang
Published: February 2021

Background

Oxidative stress and inflammation promote the development of diabetic cardiomyopathy (DCM). Therefore, inhibiting these processes may show beneficial effects in the treatment of patients with DCM. Taohuajing (THJ) is prepared using Persicae semen (Taoren), Polygonatum sibiricum (Huangjing), and Carthami flos (Honghua) and may have applications in the treatment of DCM. However, the protective effects of THJ have not been thoroughly assessed. Accordingly, in this study, we aimed to investigate the protective effects of THJ in a model of DCM and further clarify the potential mechanisms.

Methods

A type 2 diabetes mellitus model was generated using male C57BL/6 mice. Echocardiography and histopathology were used to evaluate cardiac function. The expression levels of cytokines were measured using enzyme-linked immunosorbent assays. Western blotting and small interfering RNA were used to evaluate the targets of THJ.

Results

Compared with the control group, DCM mice showed cardiac dysfunction, metabolic disorder, fibrosis, and disorganized ultrastructure, and THJ treatment significantly inhibited these changes significantly. THJ treatment also inhibited the production of reactive oxygen species (ROS) and malondialdehyde (MDA), induced the production of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), decreased the levels of pro-inflammatory cytokines, and suppressed the activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. These protective effects were abolished by sirtinol, an inhibitor of sirtuin1 (SIRT1).

Conclusions

Overall, THJ protected the heart from hyperglycemia-induced oxidative stress and inflammation in DCM mice via a mechanism involving SIRT1-mediated antioxidant proteins and suppression of the NLRP3 inflammasome.
Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin
Authors: Coleman Craig I. , Costa Olivia S. , Brescia Christopher W. , Vardar Burcu , Abdelgawwad Khaled , Sood Nitesh
Published: February 2021

Background

Diabetes increases a patient’s risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes.

Methods

This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression.

Results

We included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88–0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86–0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66–1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89–0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55–0.72).

Conclusions

In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.
Identification and characterization of heteroclitic peptides in TCR-binding positions with improved HLA-binding efficacy
Authors: Cavalluzzo Beatrice , Ragone Concetta , Mauriello Angela , Petrizzo Annacarmen , Manolio Carmen , Caporale Andrea , Vitagliano Luigi , Ruvo Menotti , Buonaguro Luigi , Tagliamonte Maria
Published: February 2021

The antigenicity as well as the immunogenicity of tumor associated antigens (TAAs) may need to be potentiated in order to break the immunological tolerance. To this aim, heteroclitic peptides were designed introducing specific substitutions in the residue at position 4 (p4) binding to TCR. The effect of such modifications also on the affinity to the major histocompatibility class I (MHC-I) molecule was assessed. The Trp2 antigen, specific for the mouse melanoma B16F10 cells, as well as the HPV-E7 antigen, specific for the TC1 tumor cell lines, were used as models. Affinity of such heteroclitic peptides to HLA was predicted by bioinformatics tools and the most promising ones were validated by structural conformational and HLA binding analyses. Overall, we demonstrated that TAAs modified at the TCR-binding p4 residue are predicted to have higher affinity to MHC-I molecules. Experimental evaluation confirms the stronger binding, suggesting that this strategy may be very effective for designing new vaccines with improved antigenic efficacy.
COVID-19 pandemic effects on orthopaedic surgeons in British Columbia
Authors: Simon Maciej J. K. , Regan William D.
Published: February 2021

Background

COVID-19 was declared a global emergency in the first quarter of 2020. It is has resulted in and continues in over a million deaths worldwide and halted medical systems and particularly elective surgeries worldwide. The aim of this study was to identify the effect of the initial COVID-19 pandemic months on orthopaedic surgeons in British Columbia.

Methods

The study surveyed (June until August 2020) 187 orthopaedic surgeons in British Columbia affiliated with the University of British Columbia or the British Columbia Orthopaedic Association using an online survey to help identify the impact of COVID-19 on patient care, work and personal life.

Results

Eighty-seven out of 187 (46.5%) orthopaedic surgeons participated in the online survey. All types of surgeries were completely cancelled for 23 respondents. Elective surgeries were cancelled for most respondents (in-hospital n = 38 and/or ambulatory n = 32). Trauma cases were reduced according to 35 respondents. Outpatient clinics were stopped initially and transferred in virtual clinics (telemedicine). Approximately 40% of respondents were afraid of infecting others (patients, family) and 25% admitted to drink more heavily. Ninety percent of respondents reported an income loss of > 15% (range 0–100%).

Conclusion

Orthopaedic surgeons and their patients have been significantly affected by the COVID-19 pandemic. Cancellation of surgeries has created an increased backlog of 32,400 orthopaedic surgeries in British Columbia. However, the COVID-19 pandemic has expedited the implementation of telemedicine, which will be a long-lasting benefit in providing healthcare.
Mesenchymal stem cell exosome-derived miR-223 alleviates acute graft-versus-host disease via reducing the migration of donor T cells
Authors: Liu Weijiang , Zhou Na , Liu Yuanlin , Zhang Wei , Li Xue , Wang Yang , Zheng Rongxiu , Zhang Yi
Published: February 2021

Background

Mesenchymal stem cells (MSCs) have been utilized in treating acute graft-versus-host disease (aGvHD) as they show strong immunosuppressive capacity through the release of various mediators, including immunosuppressive molecules, growth factors, chemokines, and exosomes. MicroRNAs (miRNAs) derived from MSC exosomes (MSCs-Exo) play a critical role in the regulation of immune responses. However, the function of miRNAs in treating aGvHD remains unknown. Here, we performed expression profiling of exosome-miRNAs from human umbilical cord MSCs (huc-MSCs) and murine compact bone MSCs (mb-MSCs) to investigate their immunoregulation effects in aGvHD.

Methods

Huc-MSCs-Exo and mb-MSCs-Exo were isolated and constructed MSCs-Exo-derived miRNA expression profiling using high-throughput sequencing. High expression of miR-223 was identified in both kinds of MSCs-Exo by bioinformatics analysis and quantitative real-time PCR (qPCR). In vitro cell crawling assay, transmigration assay and adhesion assay were subsequently applied to investigate the regulation of miR-223 on T cells. MiR-223 target gene was analyzed by western blot, luciferase analysis, and qPCR. Moreover, murine aGvHD model was established by infusing splenocytes and bone marrow nuclear cells from C57BL/6j mice (H-2Kb) into BALB/c recipient mice (H-2Kd). For therapeutic effect, MSCs or miR-223 Agomir were injected via tail vein. The general conditions of the mice in each group were monitored. Hematoxylin-eosin (H&E) staining was used to detect pathological changes of mice spleen, liver, and intestine. Mechanistically, immunofluorescence and flow cytometry were used to evaluate donor T cell migration, and enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of serum inflammatory cytokines IFN-γ, TNF-α, and IL-17.

Results

High-throughput sequencing revealed high expression of miR-223 in huc-MSCs-Exo and mb-MSCs-Exo. MiR-223 could restrain adhesion and migration of T cells by inhibiting ICAM-1 expression in mouse lymphatic endothelial cells. MiR-223Agomir infusion attenuated aGvHD clinical symptoms, reduced the donor T cell infiltration into the spleen, liver, and intestine, and decreased inflammatory cytokines IFN-γ, TNF-α, and IL-17.

Conclusion

MSCs-Exo-derived miR-223 could attenuate aGvHD in mice through decreasing donor T cell migration. Our results unveil a new role of MSCs-Exo containing miR-223 in the treatment of aGvHD.
Publisher Correction to: The rollout of the COVID-19 vaccination: what can Canada learn from Israel?
Authors: Marchildon Gregory P.
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Relationship between three-dimensional velocity of filament eruptions and CME association
Authors: Seki Daikichi , Otsuji Kenichi , Ishii Takako T. , Asai Ayumi , Ichimoto Kiyoshi
Published: February 2021

It is widely recognised that filament disappearances or eruptions are frequently associated with Coronal Mass Ejections (CMEs). Since CMEs are a major source of disturbances of the space environment surrounding the Earth, it is important to investigate these associations in detail for the better prediction of CME occurrence. However, the proportion of filament disappearances associated with CMEs is under debate. The estimates range from $$\sim$$
∼
 10 to $$\sim$$
∼
 90% and could be affected by the manners to select the events. In this study, we aim to reveal what parameters control the association between filament eruptions and CMEs. We analysed the relationships between CME associations and the physical parameters of filaments including their length, maximum ascending velocity, and direction of eruptions using 28 events of filament eruptions observed in H$$\alpha$$
α
. We found that the product of the maximum radial velocity and the filament length is well correlated with the CME occurrence. If the product is larger than $$8.0 \times 10^{6}$$

8.0
×

10
6

$$\text {km}^{2}$$

km
2

$$\text {s}^{-1}$$

s

-
1

, the filament will become a CME with a probability of 93%, and if the product is smaller than this value, it will not become a CME with a probability of 100%. We suggest a kinetic-energy threshold above which filament eruptions are associated with CMEs. Our findings also suggest the importance of measuring the velocity vector of filament eruption in three-dimensional space for the better prediction of CME occurrence.
Inference of a causal relation between low-density lipoprotein cholesterol and hypertension using mendelian randomization analysis
Authors: Go Tae-Hwa , Kwak Kyeong Im , Jang Ji-Yun , Yu Minheui , Kim Hye Sim , Kim Jang Young , Koh Sang Baek , Kang Dae Ryong
Published: February 2021

Background

It is known in some studies that higher the LDL-C, the greater the risk of developing cardiovascular disease. However, studies of the causal effects between LDL-C and hypertension are limited by their observational study design, and genetic epidemiology studies of associations between LDL-C and hypertension are lacking, as are studies using data for Koreans. In this study, we confirmed the causal effect of LDL-C on hypertension using Korean chip data.

Method

The epidemiology and genotype data were collected from the Korean Genome and Epidemiology Study conducted by the Korea National Institute of Health and covered 20,701 subjects. Single-nucleotide polymorphisms associated with LDL-C were selected (p-value < 5 × 10− 8) from the Global Lipids Genetics Consortium database, and Mendelian randomization analysis (MRA) was performed with counted genetic risk scores and weighted genetic risk scores (WGRSs) for 24 single-nucleotide polymorphisms.

Result

The assumptions for MRA were statistically confirmed, and WGRSs showed a strong association with LDL-C. Interestingly, while the relationship between LDL-C and hypertension was not statistically significant in the observational study, MRA study demonstrated that the risk of hypertension increased as LDL-C increased in both men and women.

Conclusions

The results of this study confirmed that the relationship between LDL-C and hypertension is greatly influenced by genetic information.
Binary phase hopping based spreading code authentication technique
Authors: Wang Shenran , Liu Hao , Tang Zuping , Ye Bin
Published: February 2021

Civil receivers of Global Navigation Satellite System (GNSS) are vulnerable to spoofing and jamming attacks due to their signal structures. The Spreading Code Authentication (SCA) technique is one of the GNSS message encryption identity authentication techniques. Its robustness and complexity are in between Navigation Message Authentication (NMA) and Navigation Message Encryption (NME)/Spreading Code Encryption (SCE). A commonly used spreading code authentication technique inserts unpredictable chips into the public spreading code. This method changes the signal structure, degrades the correlation of the spreading code, and causes performance loss. This paper proposes a binary phase hopping based spreading code authentication technique, which can achieve identity authentication without changing the existing signal structure. Analysis shows that this method can reduce the performance loss of the original signal and has good compatibility with the existing receiver architecture.
Optimization and comparison of ℽ-aminobutyric acid (GABA) production by LAB in soymilk using RSM and ANN models
Authors: Rayavarapu Bhargavi , Tallapragada Padmavathi , MS Usha
Published: February 2021

Background

ℽ-Aminobutyric acid (GABA) is a non-proteinaceous amino acid. In the mammalian nervous system, GABA functions as an inhibitory neurotransmitter. The present study focused on screening and optimization of ℽ-aminobutyric acid (GABA) yield by lactic acid bacteria by using soymilk as basal media. Lactobacillus fermentum (Lb. fermentum) was isolated from sourdough. The qualitative confirmation of GABA production by Lb. fermentum was observed by detecting colored spots on thin layer chromatography plate (TLC) and comparing it with standard GABA spot. The GABA from bacteria is confirmed by its molecular mass using mass spectrophotometry analysis (MS analysis). Single variable experiments were conducted for various physical and nutritional parameters, and determined the GABA content produced from Lb. fermentum, viable bacterial count, and pH of the fermented soymilk medium. Experimental data were authenticated by using response surface method (RSM) and artificial neural network (ANN) model.

Results

The results demonstrated that through single variable experiments, the yield of GABA and the viable bacterial cells increased in soymilk containing one percent of glucose, monosodium glutamate (MSG), and inoculum volume incubated at 37 °C, 48 h at pH 5. According to RSM results, the interaction of the highest concentration of MSG (1.5%) and mid glucose concentration (1.156%) yielded maximum GABA (5.54 g/L). The experimental data were in good agreement with two optimization models. The RSM models showed less error percentage than that of the ANN model.

Conclusion

This study indicates that soymilk is the best basal substrate for GABA production and growth of Lb. fermentum compared to synthetic media. Lb. fermentum can be explored further by food and pharmaceutical industries for the development of functional foods and therapeutic purposes.
Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas
Authors: Eder Joseph P. , Doroshow Deborah B. , Do Khanh T. , Keedy Vicki L. , Sklar Jeffrey S. , Glazer Peter , Bindra Ranjit , Shapiro Geoffrey I.
Published: February 2021

PURPOSE

Tumors with neomorphic mutations in IDH1/2 have defective homologous recombination repair, resulting in sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition. The Olaparib Combination trial is a phase II, open-label study in which patients with solid tumors harboring IDH1/2 mutations were treated with olaparib as monotherapy, with objective response and clinical benefit rates as the primary end points.

METHODS

Ten patients with IDH1/2-mutant tumors by next-generation sequencing were treated with olaparib 300 mg twice daily.

RESULTS

Three of five patients with chondrosarcomas had clinical benefit, including one patient with a partial response and two with stable disease lasting > 7 months. A patient with pulmonary epithelioid hemangioendothelioma had stable disease lasting 11 months. In contrast, clinical benefit was not observed among four patients with cholangiocarcinoma.

CONCLUSION

These results indicate preliminary activity of PARP inhibition in patients with IDH1/2-mutant chondrosarcoma and pulmonary epithelioid hemangioendothelioma. Further studies of PARP inhibitors alone and in combination in this patient population are warranted.