bluuebunny/crossref_metadata_2025 huggingface dataset:
Theranostic nanoplatform to target macrophages enables the inhibition of atherosclerosis progression and fluorescence imaging of plaque in ApoE(−/−) mice
Authors: Wang Qi , Wang Yong , Liu Siwen , Sha Xuan , Song Xiaoxi , Dai Yue , Zhao Mingming , Cai Lulu , Xu Kai , Li Jingjing
Published: July 2021

Background

Rupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property. Therefore, the early diagnosis and inhibition of atherosclerotic plaque progress still be a vital task.

Results

In this study, we presented the development of composite mesoporous silica nanoparticle (Ru(bpy)3@SiO2-mSiO2, CMSN)-based nanomedicines (NMs) (Ru(bpy)3@SiO2-mSiO2@SRT1720@AntiCD36, CMSN@SRT@Anti) for accurate diagnosis and treatment of atherosclerosis (AS). In vitro cell experiments showed that both RAW264.7 and oxidized low density lipoprotein (ox-LDL)-stimulated RAW264.7 cells could significantly uptake CMSN@SRT@Anti. Conversely, little fluorescence signal could be observed in CMSN@SRT group, showing the excellent targeting ability of CMSN@SRT@Anti to Class II scavenger receptor, CD36 on macrophage. Additionally, such fluorescence signal was significantly stronger in ox-LDL-stimulated RAW264.7 cells, which might benefit from the upregulated expression of CD36 on macrophages after ox-LDL treatment. For another, compared with free SRT1720, CMSN@SRT@Anti had a better and more significant effect on the inhibition of macrophage foaming process, which indicated that drug-carrying mesoporous silicon with targeting ability could enhance the efficacy of SRT1720. Animal experimental results showed that after the abdominal injection of CMSN@SRT@Anti, the aortic lesions of ApoE-/-mice could be observed with obvious and persistent fluorescence signals. After 4 weeks post-treatment, the serum total cholesterol, aortic plaque status and area were significantly improved in the mouse, and the effect was better than that in the free SRT1720 group or the CMSN@SRT group.

Conclusions

The designed CMSN@SRT@Anti with excellent biocompatibility, high-performance and superior atherosclerosis-targeting ability has great potential for accurate identification and targeted therapy of atherosclerotic diseases.

Graphic abstract
Curcumin loaded sub-30 nm targeting therapeutic lipid nanoparticles for synergistically blocking nasopharyngeal cancer growth and metastasis
Authors: Luo Haiming , Lu Lisen , Liu Ni , Li Qingqing , Yang Xiaoquan , Zhang Zhihong
Published: July 2021

Systemic chemotherapy is still the primary treatment for advanced-stage nasopharyngeal carcinoma (NPC), but only limited therapeutic success has been achieved in the past decade because of drug resistance and systemic toxicity. Curcumin (Cur) is an effective alternative to chemotherapeutics because it showed remarkable therapeutic potential in the treatment of NPC. However, lack of tissue specificity and poor penetration in solid tumors are the major obstacles to effective therapy. Therefore, in this work, a self-assembled sub-30 nm therapeutic lipid nanoparticle loaded with Cur, named as Cur@α-NTP-LN, was constructed, specifically targeting scavenger receptor class B member 1 (SR-B1) and enhancing its therapeutic effects on NPC in vivo. Our results showed that Cur@α-NTP-LNs were effective and superior to free Cur on NPC cell-specific targeting, suppressing cell proliferation and inducing cell apoptosis. In vivo and ex vivo optical imaging revealed that Cur@α-NTP-LNs exerted high targeting efficiency, specifically accumulating in NPC xenograft tumors and delivering Cur into the tumor center after systemic administration. Furthermore, Cur@α-NTP-LNs exhibited a remarkable inhibitory effect on the growth of NPC subcutaneous tumors, with over 71 and 47% inhibition compared to Cur- and α-NTP-LNs-treated groups, respectively. In addition, Cur@α-NTP-LNs almost blocked NPC metastasis in a lung metastasis model of NPC and significantly improved the survival rate. Thus, the sub-30 nm Cur@α-NTP-LNs enhanced the solubility of Cur and demonstrated the ability of targeted Cur delivery into the center of the solid NPC tumor, performing synergistic inhibitory effects on the growth of NPC tumor and its metastasis with high efficiency.
An explainable supervised machine learning predictor of acute kidney injury after adult deceased donor liver transplantation
Authors: Zhang Yihan , Yang Dong , Liu Zifeng , Chen Chaojin , Ge Mian , Li Xiang , Luo Tongsen , Wu Zhengdong , Shi Chenguang , Wang Bohan , Huang Xiaoshuai , Zhang Xiaodong , Zhou Shaoli , Hei Ziqing
Published: July 2021

Background

Early prediction of acute kidney injury (AKI) after liver transplantation (LT) facilitates timely recognition and intervention. We aimed to build a risk predictor of post-LT AKI via supervised machine learning and visualize the mechanism driving within to assist clinical decision-making.

Methods

Data of 894 cases that underwent liver transplantation from January 2015 to September 2019 were collected, covering demographics, donor characteristics, etiology, peri-operative laboratory results, co-morbidities and medications. The primary outcome was new-onset AKI after LT according to Kidney Disease Improving Global Outcomes guidelines. Predicting performance of five classifiers including logistic regression, support vector machine, random forest, gradient boosting machine (GBM) and adaptive boosting were respectively evaluated by the area under the receiver-operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. Model with the best performance was validated in an independent dataset involving 195 adult LT cases from October 2019 to March 2021. SHapley Additive exPlanations (SHAP) method was applied to evaluate feature importance and explain the predictions made by ML algorithms.

Results

430 AKI cases (55.1%) were diagnosed out of 780 included cases. The GBM model achieved the highest AUC (0.76, CI 0.70 to 0.82), F1-score (0.73, CI 0.66 to 0.79) and sensitivity (0.74, CI 0.66 to 0.8) in the internal validation set, and a comparable AUC (0.75, CI 0.67 to 0.81) in the external validation set. High preoperative indirect bilirubin, low intraoperative urine output, long anesthesia time, low preoperative platelets, and graft steatosis graded NASH CRN 1 and above were revealed by SHAP method the top 5 important variables contributing to the diagnosis of post-LT AKI made by GBM model.

Conclusions

Our GBM-based predictor of post-LT AKI provides a highly interoperable tool across institutions to assist decision-making after LT.

Graphic abstract
Patterns and predictors of gestational weight gain in Addis Ababa, Central Ethiopia: a prospective cohort study
Authors: Asefa Fekede , Cummins Allison , Dessie Yadeta , Foureur Maralyn , Hayen Andrew
Published: July 2021

Introduction

Gaining excessive or inadequate gestational weight is associated with many adverse maternal and fetal outcomes. Inadequate gestational weight gain (GWG) increases the risk of fetal growth restriction, pre-term birth, and low birth weight. It is a public health concern in sub-Saharan Africa. The aim of this study was to assess the patterns and predictors of GWG in Addis Ababa, Ethiopia.

Methods

We conducted a prospective cohort study among pregnant women who attended antenatal care in health centres in Addis Ababa, from January to September 2019. Data were collected by a structured questionnaire and checklists and analysed using Stata version-14. Weight at or before 16 weeks gestation was used as a proxy for pre-pregnancy weight. Women’s height and baseline weight were measured by data collectors, and we obtained weight at the end of the 24th and 36th weeks of gestation from women’s medical records. GWG was categorized as inadequate, adequate and excessive based on the United States Institute of Medicine criteria. Predictors of GWG were identified using multinomial logistic regression.

Results

A total of 395 pregnant women were enrolled in the study. GWG was assessed for 369 (93%) women. The median GWG was 8.7 kg with inter quartile ranges (25th, 75th percentiles) of 7.0 kg and 11.6 kg. More than two-third of the participants, 248 (67.2% [95% CI: 62.2, 72.0%]), gained inadequate weight; 103 (27.9% [95% CI: 23.4, 32.8%]) gained adequate weight; and 18 (4.9% [95% CI: 2.9%, 7.6%]) gained excessive weight. Three quarters (75%) of underweight women gained inadequate gestational weight, whereas 43% of overweight or obese women gained inadequate gestational weight. Being underweight (AOR = 3.30 [95% CI: 1.32, 8.24]) or normal weight (AOR = 2.68 [95% CI: 1.37, 5.24]) before pregnancy increased the odds of gaining inadequate gestational weight compared to overweight or obese women. Not having paid employment was associated with higher odds of gaining inadequate gestational weight compared to women employed outside the home (AOR = 2.17 [95% CI: 1.16, 4.07]).

Conclusions

Most pregnant women in Addis Ababa gain inadequate gestational weight. In particular, three quarters of underweight women gained inadequate gestational weight. Being underweight, normal weight or having no paid employment were associated with higher odds of inadequate GWG. Promoting adequate GWG in Addis Ababa among underweight and normal weight women may be an important public health initiative.
Association of endothelial nitric oxide synthase gene variants with preeclampsia
Authors: Shaheen Ghazala , Jahan Sarwat , Bibi Nousheen , Ullah Asmat , Faryal Rani , Almajwal Ali , Afsar Tayyaba , Al-disi Dara , Abulmeaty Mahmoud , Al Khuraif Abdulaziz Abdullah , Arshad Mohammed , Razak Suhail
Published: July 2021

Background

Preeclampsia (PE) is a complex pregnancy hypertensive disorder with multifaceted etiology. The endothelial nitric oxide synthase (eNOS) gene and nitric oxide (NO) levels has been reported to be associated with PE predisposition in various populations. Therefore, present study was designed to investigate the role of NO levels andeNOSgene variants in preeclamptic women in Pakistan.

Methods

A total of 600 women were evaluated, 188 of PE with mild features, 112 of PE with severe features and 300 normotensive pregnant women. NO levels were detected by Greiss reaction method and genotyping following sequencing was conducted foreNOSgene variants. Furtherinsilicostudies were performed to get insights into the structural and functional impact of identifies mutation on eNOS protein as well as on protein regulation.

Results

Reduced concentrations of NO were reported in all PE groups (p < 0.05) as compared to controls. The frequency of c.894 T (p.298Asp) and g.-786C alleles were significantly associated with PE. In addition, novel homozygous variant g.2051G > A was also significantly associated with PE when compared to normotensive women. Dynamic simulation studies revealed that Glu298Asp mutation destabilize the protein molecule and decrease the overall stability of eNOS protein. Molecular docking analysis of mutant promoter with transcription factors STAT3 and STAT6 proposed changes in protein regulation upon these reported mutations in upstream region of the gene.

Conclusion

Considering the results of current study, the functional alterations induced by these variants may influence the bioavailability of NO and represents a genetic risk factor for increased susceptibility to PE. However, large studies or meta-analysis are necessary to validate these findings.
Influence of intensified adherence counselling on viral load suppression of people receiving antiretroviral therapy at a health centre IV in southwestern Uganda: a qualitative study
Authors: Pius Atwau , Josephine Najjuma Nambi , Erick Sibo , Winifred Agoa , Rita Mukashyaka , Silverjoseph Okoli , Lucy Ezatiru , Novatus Nyemara
Published: July 2021

Background

The prevalence of Human Immunodeficiency Virus (HIV) among adults and children in Uganda is 6.2% and 0.5% respectively. The prevalence of viral load suppression in Uganda among all adults and children living with HIV is 59.6% and 39.3% respectively. High viral load compromises on the quality of life of an individual, and as well increases on the risk of transmission of the virus to the unborn for pregnant mothers and to the spouse. The UNAID 90-90-90 campaign recommends that 90% know their status, 90% get treatment and 90% have viral suppression. Non-adherence to Antiretroviral Therapy (ART) is one of the causes of the high viral load. The world health organization recommends Intensified Adherence Counselling (IAC) be given to all individuals with a high viral load. The perceptions, attitudes and practices of people receiving IAC is important in understanding how best IAC should be implemented.

Methods

A qualitative study was done among 30 purposively selected individuals/guardians of children receiving ART and IAC at Kyabugimbi Health Center Four [HC IV (mini-hospital headed by a medical doctor)]. Data collected from Focus Group Discussion as audio-recordings in local language (Runyankole) was transcribed and later translated into English. Translated transcripts were analyzed manually using thematic content analysis.

Results

The major themes identified include: adherence to ART; change of attitude towards ART after IAC, IAC expectation and outcomes, IAC and stigma, and improving social support through IAC for PLWHIV.

Conclusion

Participating in IAC to be informative and led to change in their perceptions of HIV and better understanding the reasons for adherence to ART. IAC influenced the change in attitude and behavior thus seeking social support and mitigate stigma, which lead to a better ART adherence. However, there is need to improve on the way it is delivered both in structural setting and break down and packaging of information.
A day in the life: a qualitative study of clinical decision-making and uptake of neurorehabilitation technology
Authors: Celian Courtney , Swanson Veronica , Shah Maahi , Newman Caitlin , Fowler-King Bridget , Gallik Sarah , Reilly Kaitlin , Reinkensmeyer David J. , Patton James , Rafferty Miriam R.
Published: July 2021

Background

Neurorehabilitation engineering faces numerous challenges to translating new technologies, but it is unclear which of these challenges are most limiting. Our aim is to improve understanding of rehabilitation therapists’ real-time decision-making processes on the use of rehabilitation technology (RT) in clinical treatment.

Methods

We used a phenomenological qualitative approach, in which three OTs and two PTs employed at a major, technology-encouraging rehabilitation hospital wrote vignettes from a written prompt describing their RT use decisions during treatment sessions with nine patients (4 with stroke, 2 traumatic brain injury, 1 spinal cord injury, 1 with multiple sclerosis). We then coded the vignettes using deductive qualitative analysis from 17 constructs derived from the RT literature and the Consolidated Framework for Implementation Research (CFIR). Data were synthesized using summative content analysis.

Results

Of the constructs recorded, the five most prominent are from CFIR determinants of: (i) relative advantage, (ii) personal attributes of the patients, (iii) clinician knowledge and beliefs of the device/intervention, (iv) complexity of the devices including time and setup, and (v) organizational readiness to implement. Therapists characterized candidate RT as having a relative disadvantage compared to conventional treatment due to lack of relevance to functional training. RT design also often failed to consider the multi-faceted personal attributes of the patients, including diagnoses, goals, and physical and cognitive limitations. Clinicians’ comfort with RT was increased by their previous training but was decreased by the perceived complexity of RT. Finally, therapists have limited time to gather, setup, and use RT.

Conclusions

Despite decades of design work aimed at creating clinically useful RT, many lack compatibility with clinical translation needs in inpatient neurologic rehabilitation. New RT continue to impede the immediacy, versatility, and functionality of hands-on therapy mediated treatment with simple everyday objects.
Natural products provide a new perspective for anti-complement treatment of severe COVID-19: a review
Authors: Fan Yadong , Wang Ying , Yu Shuang , Chang Jun , Yan Yiqi , Wang Yiyang , Bian Yuhong
Published: July 2021

Exaggerated immune response and cytokine storm are accounted for the severity of COVID-19, including organ dysfunction, especially progressive respiratory failure and generalized coagulopathy. Uncontrolled activation of complement contributes to acute and chronic inflammation, the generation of cytokine storm, intravascular coagulation and cell/tissue damage, which may be a favorable target for the treatment of multiple organ failure and reduction of mortality in critically ill patients with COVID-19. Cytokine storm suppression therapy can alleviate the symptoms of critically ill patients to some extent, but as a remedial etiological measure, its long-term efficacy is still questionable. Anti-complement therapy has undoubtedly become an important hotspot in the upstream regulation of cytokine storm. However, chemosynthetic complement inhibitors are expensive, and their drug resistance and long-term side effects require further investigation. New complement inhibitors with high efficiency and low toxicity can be obtained from natural products at low development cost. This paper puts forward some insights of the development of natural anti-complement products in traditional Chinese medicine, that may provide a bright perspective for suppressing cytokine storm in critically ill patients with COVID-19.
Age-related increase in caveolin-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons
Authors: Ha Tae-Young , Choi Yu Ree , Noh Hye Rin , Cha Seon-Heui , Kim Jae-Bong , Park Sang Myun
Published: July 2021

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.
Reliability of mechanical ventilation during continuous chest compressions: a crossover study of transport ventilators in a human cadaver model of CPR
Authors: Orlob Simon , Wittig Johannes , Hobisch Christoph , Auinger Daniel , Honnef Gabriel , Fellinger Tobias , Ristl Robin , Schindler Otmar , Metnitz Philipp , Feigl Georg , Prause Gerhard
Published: July 2021

Background

Previous studies have stated that hyperventilation often occurs in cardiopulmonary resuscitation (CPR) mainly due to excessive ventilation frequencies, especially when a manual valve bag is used. Transport ventilators may provide mandatory ventilation with predetermined tidal volumes and without the risk of hyperventilation. Nonetheless, interactions between chest compressions and ventilations are likely to occur. We investigated whether transport ventilators can provide adequate alveolar ventilation during continuous chest compression in adult CPR.

Methods

A three-period crossover study with three common transport ventilators in a cadaver model of CPR was carried out. The three ventilators ‘MEDUMAT Standard²’, ‘Oxylog 3000 plus’, and ‘Monnal T60’ represent three different interventions, providing volume-controlled continuous mandatory ventilation (VC-CMV) via an endotracheal tube with a tidal volume of 6 mL/kg predicted body weight. Proximal airflow was measured, and the net tidal volume was derived for each respiratory cycle. The deviation from the predetermined tidal volume was calculated and analysed. Several mixed linear models were calculated with the cadaver as a random factor and ventilator, height, sex, crossover period and incremental number of each ventilation within the period as covariates to evaluate differences between ventilators.

Results

Overall median deviation of net tidal volume from predetermined tidal volume was − 21.2 % (IQR: 19.6, range: [− 87.9 %; 25.8 %]) corresponding to a tidal volume of 4.75 mL/kg predicted body weight (IQR: 1.2, range: [0.7; 7.6]). In a mixed linear model, the ventilator model, the crossover period, and the cadaver’s height were significant factors for decreased tidal volume. The estimated effects of tidal volume deviation for each ventilator were − 14.5 % [95 %-CI: −22.5; −6.5] (p = 0.0004) for ‘Monnal T60’, − 30.6 % [95 %-CI: −38.6; −22.6] (p < 0.0001) for ‘Oxylog 3000 plus’ and − 31.0 % [95 %-CI: −38.9; −23.0] (p < 0.0001) for ‘MEDUMAT Standard²’.

Conclusions

All investigated transport ventilators were able to provide alveolar ventilation even though chest compressions considerably decreased tidal volumes. Our results support the concept of using ventilators to avoid excessive ventilatory rates in CPR. This experimental study suggests that healthcare professionals should carefully monitor actual tidal volumes to recognise the occurrence of hypoventilation during continuous chest compressions.
Tapering of prescribed opioids in patients with long-term non-malignant pain (TOPIO)—efficacy and effects on pain, pain cognitions, and quality of life: a study protocol for a randomized controlled clinical trial with a 12-month follow-up
Authors: Henrik Grelz , Patrik Midlöv , Anders Håkansson , Ulf Jakobsson , Marcelo Rivano Fischer , Åsa Ringqvist
Published: July 2021

Background

Opioids are still widely prescribed to long-term pain patients although they are no longer recommended for long-term treatments due to poor evidence for long-term efficacy, risks of serious side effects, and the possibility of inducing opioid hyperalgesia. In a Cochrane study from 2017, the authors identified an urgent need for more randomized controlled trials investigating the efficiency and effects of opioid tapering.

The study aimed to assess (1) the efficiency of a structured intervention in causing stable reductions of opioid consumption in a population with long-term non-malignant pain and (2) effects on pain, pain cognitions, physical and mental health, quality of life, and functioning in response to opioid tapering.

Methods

The study is a randomized controlled trial. The sample size was set to a total of 140 individuals after estimation of power and dropout. Participants will be recruited from a population with long-term non-malignant pain who will be randomly allocated to (1) the start of tapering immediately or (2) the control group who return to usual care and will commence tapering of opioids 4 months later. A 12-month follow-up is included.

When all follow-ups are closed, data from the Swedish drug register of the National Board of Health and Welfare will be collected and individual mean daily opioid dose in morphine equivalents will be calculated at three time points: baseline, 4 months, and 12 months after the start of the intervention. At the same time points, participants fill out the following questionnaires: Numeric Pain Rating Scale (NPRS), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing Scale (PCS), Chronic Pain Acceptance Questionnaire (CPAQ-8), Hospital Anxiety and Depression Scale (HADS), and RAND-36. At baseline and follow-up, a clinical assessment of opioid use disorder is performed.

Discussion

A better understanding of the efficiency and effects of opioid tapering could possibly facilitate attempts to taper opioid treatments, which might prove beneficial for both the individual and society.

Trial registration

ClinicalTrials.gov NCT03485430. Retrospectively registered on 26 March 2018, first release date. “Tapering of Long-term Opioid Therapy in Chronic Pain Population. RCT with 12 Months Follow up (TOPIO).” First patient in trial 22 March 2018.
Detailed statistical analysis plan for the short-term versus long-term mentalisation-based therapy for outpatients with subthreshold or diagnosed borderline personality disorder randomised clinical trial (MBT-RCT)
Authors: Juul Sophie , Simonsen Sebastian , Poulsen Stig , Lunn Susanne , Sørensen Per , Bateman Anthony , Jakobsen Janus Christian
Published: July 2021

Background

Psychotherapy for borderline personality disorder is often extensive and resource-intensive. Mentalisation-based therapy is a psychodynamically oriented treatment option for borderline personality disorder, which includes a case formulation, psychoeducation, and group and individual therapy. The evidence on short-term compared with long-term mentalisation-based therapy is currently unknown.

Methods/design

The Short-Term MBT Project (MBT-RCT) is a single-centre, parallel-group, investigator-initiated, randomised clinical superiority trial in which short-term (20 weeks) will be compared with long-term (14 months) mentalisation-based therapy for outpatients with subthreshold or diagnosed borderline personality disorder. Outcome assessors, data managers, the data safety and monitoring committee, statisticians, and decision-makers will be blinded to treatment allocation. Participants will be assessed before randomisation and at 8, 16, and 24 months after randomisation. The primary outcome will be the severity of borderline symptomatology assessed with the Zanarini Rating Scale for Borderline Personality Disorder. Secondary outcomes will be functional impairment (Work and Social Adjustment Scale), quality of life (Short-Form Health Survey 36—mental component), global functioning (Global Assessment of Functioning), and proportion of participants with severe self-harm. In this paper, we present a detailed statistical analysis plan including a comprehensive explanation of the planned statistical analyses, methods to handle missing data, and assessments of the underlying statistical assumptions. Final statistical analyses will be conducted independently by two statisticians following the present plan.

Discussion

We have developed this statistical analysis plan before unblinding of the trial results in line with the Declaration of Helsinki and the International Conference on Harmonization of Good Clinical Practice Guidelines, which should increase the validity of the MBT-RCT trial by mitigation of analysis bias.

Trial registration

ClinicalTrials.gov NCT03677037. Registered on 19 September 2018
Randomised study within a trial (SWAT) to evaluate personalised versus standard text message prompts for increasing trial participant response to postal questionnaires (PROMPTS)
Authors: Cureton Lucy , Marian Ioana R. , Barber Vicki S. , Parker Adwoa , Torgerson David J. , Hopewell Sally
Published: July 2021

Background

Use of a person’s name in a text message has been shown to be effective in instigating behaviour change. We evaluated the effectiveness of a personalised text message (including the recipient’s name) versus a standardised text message for prompting a response from trial participants to complete and return postal follow-up questionnaires.

Methods

Using a randomised study within a trial (SWAT) embedded within the host GRASP (Getting it Right: Addressing Shoulder Pain) trial, participants who provided a mobile telephone number were randomised (1:1) by a central computer system to receive either (1) a personalised text message which included their name or (2) a standard text message. Text messages were sent by the trial office on the same day as the 6-month GRASP follow-up questionnaire. The primary outcome was questionnaire response rate, defined as the proportion of 6-month GRASP follow-up questionnaires returned by participants. Secondary outcomes included time to response, the proportion of participants sent a reminder follow-up questionnaire, and cost.

Results

Between March 2017 and May 2019 (recruitment period for GRASP trial), 618 participants were randomised to a personalised (n = 309) or standard (n = 309) text message and all were included in the analysis. The overall questionnaire response rate was 87% (n = 537/618); 90% (n = 277/309) of participants responded in the personalised text message group compared to 84% (n = 260/309) in the standard text message group (relative risk (RR) 1.07; 95% CI 1.00 to 1.13). Participants randomised to receive the personalised text message were more likely to return their initial postal questionnaire than those who received the standard text message (n = 185/309; 60% vs. n = 160/309; 52%) (RR 1.16; 95% CI 1.00 to 1.33); this represents an absolute percentage difference between intervention groups of 8%. Post hoc subgroup analysis showed that males under 65 years were the group most likely to return their initial questionnaire if they received a personalised text message.

Conclusion

Overall, participants who received a personalised text message were more likely to return their questionnaire than those who received the standard text message.

Trial registration

GRASP Trial ISRCTN16539266; SWAT Repository ID 35
Epigenetic rewriting at centromeric DNA repeats leads to increased chromatin accessibility and chromosomal instability
Authors: Decombe Sheldon , Loll François , Caccianini Laura , Affannoukoué Kévin , Izeddin Ignacio , Mozziconacci Julien , Escudé Christophe , Lopes Judith
Published: July 2021

Background

Centromeric regions of human chromosomes contain large numbers of tandemly repeated α-satellite sequences. These sequences are covered with constitutive heterochromatin which is enriched in trimethylation of histone H3 on lysine 9 (H3K9me3). Although well studied using artificial chromosomes and global perturbations, the contribution of this epigenetic mark to chromatin structure and genome stability remains poorly known in a more natural context.

Results

Using transcriptional activator-like effectors (TALEs) fused to a histone lysine demethylase (KDM4B), we were able to reduce the level of H3K9me3 on the α-satellites repeats of human chromosome 7. We show that the removal of H3K9me3 affects chromatin structure by increasing the accessibility of DNA repeats to the TALE protein. Tethering TALE-demethylase to centromeric repeats impairs the recruitment of HP1α and proteins of Chromosomal Passenger Complex (CPC) on this specific centromere without affecting CENP-A loading. Finally, the epigenetic re-writing by the TALE-KDM4B affects specifically the stability of chromosome 7 upon mitosis, highlighting the importance of H3K9me3 in centromere integrity and chromosome stability, mediated by the recruitment of HP1α and the CPC.

Conclusion

Our cellular model allows to demonstrate the direct role of pericentromeric H3K9me3 epigenetic mark on centromere integrity and function in a natural context and opens interesting possibilities for further studies regarding the role of the H3K9me3 mark.
An implementation science approach to evaluating pathogen whole genome sequencing in public health
Authors: Ferdinand Angeline S. , Kelaher Margaret , Lane Courtney R. , da Silva Anders Gonçalves , Sherry Norelle L. , Ballard Susan A. , Andersson Patiyan , Hoang Tuyet , Denholm Justin T. , Easton Marion , Howden Benjamin P. , Williamson Deborah A.
Published: July 2021

Background

Pathogen whole genome sequencing (WGS) is being incorporated into public health surveillance and disease control systems worldwide and has the potential to make significant contributions to infectious disease surveillance, outbreak investigation and infection prevention and control. However, to date, there are limited data regarding (i) the optimal models for integration of genomic data into epidemiological investigations and (ii) how to quantify and evaluate public health impacts resulting from genomic epidemiological investigations.

Methods

We developed the Pathogen Genomics in Public HeAlth Surveillance Evaluation (PG-PHASE) Framework to guide examination of the use of WGS in public health surveillance and disease control. We illustrate the use of this framework with three pathogens as case studies: Listeria monocytogenes, Mycobacterium tuberculosis and SARS-CoV-2.

Results

The framework utilises an adaptable whole-of-system approach towards understanding how interconnected elements in the public health application of pathogen genomics contribute to public health processes and outcomes. The three phases of the PG-PHASE Framework are designed to support understanding of WGS laboratory processes, analysis, reporting and data sharing, and how genomic data are utilised in public health practice across all stages, from the decision to send an isolate or sample for sequencing to the use of sequence data in public health surveillance, investigation and decision-making. Importantly, the phases can be used separately or in conjunction, depending on the need of the evaluator. Subsequent to conducting evaluation underpinned by the framework, avenues may be developed for strategic investment or interventions to improve utilisation of whole genome sequencing.

Conclusions

Comprehensive evaluation is critical to support health departments, public health laboratories and other stakeholders to successfully incorporate microbial genomics into public health practice. The PG-PHASE Framework aims to assist public health laboratories, health departments and authorities who are either considering transitioning to whole genome sequencing or intending to assess the integration of WGS in public health practice, including the capacity to detect and respond to outbreaks and associated costs, challenges and facilitators in the utilisation of microbial genomics and public health impacts.
Differential expression of micro RNA-29 family in non-diabetic adults of diabetic and non-diabetic parents
Authors: Abbas Uzair , Imdad Bushra , Mughal Sikander Adil , Baloch Israr Ahmed , Khan Afshan Mehboob , Kamran Durr-e-Sameen
Published: July 2021

Objective

MicroRNAs are known to regulate 60% of genes at post translational level. MicroRNAs including Micro RNA-29 family play a vital role in cellular activities and have validate role in numerous metabolic disorders inclusive of diabetes mellitus and its complications. While micro RNA profile changes years before the occurrence of disease. This cross-sectional study was conducted in non-diabetic adults of diabetic and non-diabetic parents to explore the early changes in expression of micro RNA-29 family as it can be served as early biomarker of type 2 diabetes in non-diabetic adults. This study was conducted from January 2019 to January 2021. Micro RNA was extracted from plasma of 50 participants and expression was compared through qPCR. While data was analyzed through SPSS version 21.0.

Results

29a and 29b had lower expression in participants with family history of DM compared to those having no family history of DM (P < 0.0001). While micro RNA 29c was found to be significantly higher in participants with positive family history of type 2 diabetes as compared to those without family history of diabetes (P = 0.001).
Pleth variability index and fluid management practices: a multicenter service evaluation
Authors: Forget Patrice , Lacroix Simon , Deflandre Eric P. , Pirson Anne , Hustinx Nicolas , Simonet Olivier , Wandji Fabrice , von Montigny Serge , Amraoui Jibba
Published: July 2021

Objectives

The introduction of a new technology has the potential to modify clinical practices, especially if easy to use, reliable and non-invasive. This observational before/after multicenter service evaluation compares fluid management practices during surgery (with fluids volumes as primary outcome), and clinical outcomes (secondary outcomes) before and after the introduction of the Pleth Variability Index (PVI), a non-invasive fluid responsiveness monitoring.

Results

In five centers, 23 anesthesiologists participated during a 2-years period. Eighty-eight procedures were included. Median fluid volumes infused during surgery were similar before and after PVI introduction (respectively, 1000 ml [interquartile range 25–75 [750–1700] and 1000 ml [750–2000]). The follow-up was complete for 60 from these and outcomes were similar. No detectable change in the fluid management was observed after the introduction of a new technology in low to moderate risk surgery. These results suggest that the introduction of a new technology should be associated with an implementation strategy if it is intended to be associated with changes in clinical practice.
A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies
Authors: Razeghian Ehsan , Nasution Mahyuddin K. M. , Rahman Heshu Sulaiman , Gardanova Zhanna R. , Abdelbasset Walid Kamal , Aravindhan Surendar , Bokov Dmitry O. , Suksatan Wanich , Nakhaei Pooria , Shariatzadeh Siavash , Marofi Faroogh , Yazdanifar Mahboubeh , Shamlou Somayeh , Motavalli Roza , Khiavi Farhad Motavalli
Published: July 2021

To date, two chimeric antigen receptors (CAR)-T cell products from autologous T cells have been approved by The United States Food and Drug Administration (FDA). The case-by-case autologous T cell generation setting is largely considered as a pivotal restraining cause for its large-scale clinical use because of the costly and prolonged manufacturing procedure. Further, activated CAR-T cells mainly express immune checkpoint molecules, including CTLA4, PD1, LAG3, abrogating CAR-T anti-tumor activity. In addition, CAR-T cell therapy potently results in some toxicity, such as cytokine releases syndrome (CRS). Therefore, the development of the universal allogeneic T cells with higher anti-tumor effects is of paramount importance. Thus, genome-editing technologies, in particular, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 are currently being used to establish “off-the-shelf” CAR-T cells with robust resistance to immune cell-suppressive molecules. In fact, that simultaneous ablation of PD-1, T cell receptor alpha constant (TRAC or TCR), and also β-2 microglobulin (B2M) by CRISPR-Cas9 technique can support the manufacture of universal CAR-T cells with robust resistance to PD-L1. . Indeed, the ablation of β2M or TARC can severely hinder swift elimination of allogeneic T cells those express foreign HLA-I molecules, and thereby enables the generation of CAR-T cells from allogeneic healthy donors T cells with higher persistence in vivo. Herein, we will deliver a brief overview of the CAR-T cell application in the context of tumor immunotherapy. More importantly, we will discuss recent finding concerning the application of genome editing technologies for preparing universal CAR-T cells or cells that can effectively counter tumor escape, with a special focus on CRISPR-Cas9 technology.
RETRACTED ARTICLE: Design and Implementation of Track and Field Training Information Collection and Feedback System Based on Multi-sensor Information Fusion
Authors: Li Ling , Li Chengliang
Published: July 2021

Track and field sports are known as the "mother of sports". Whether in the field of athletics, fitness, or education, modern track and field sports have developed rapidly. The field of athletics has reached the point where it challenges the limits of humans. The development of China is inseparable from the support of science and technology, and it is inseparable from human scientific research on track and field sports. In order to improve the scientific level of track and field training methods and develop our country's sports industry, this paper designs a track and field training information collection and feedback system based on multi-sensor information fusion. In the method part, this article briefly introduces the content of track and field sports, the mode of multi-sensor information fusion and the existing sports information collection system, using weight coefficient fusion method, D-S evidence theory algorithm and Kalman filter algorithm. This paper designs an information collection and feedback system based on multi-sensor information fusion, and conducts demand analysis, comparative analysis, and data record analysis on this system. By designing the experimental group and the control group, it can be seen that the average performance of the two groups of athletes in the 50-meter run in 8 weeks has improved, and the data of the experimental group and the control group show significant differences. After the experiment, the average performance of the male athletes in the control group increased from around 8.32 to around 8.12, an increase of 4.7%. The performance of male athletes in the experimental group increased from 8.37 to 7.92, an increase of 5.6%. It can also be known that before the experiment, the average performance of the athletes in the selected control group was due to the experimental group, but after 8 weeks of experiment, the increase in the experimental group was higher than that of the control group. This shows that the data collection and feedback system using multi-sensor information fusion can be more accurately and differentiatedly applied to track and field training, and can find problems in athletes, so as to prescribe the right medicine.
Regularly ideal invariant convergence of double sequences
Authors: Pancaroǧlu Akın Nimet
Published: July 2021

In this paper, we introduce the notions of regularly invariant convergence, regularly strongly invariant convergence, regularlyp-strongly invariant convergence, regularly$(\mathcal{I}_{\sigma },\mathcal{I}^{\sigma }_{2})$(Iσ,I2σ)-convergence, regularly$(\mathcal{I}_{\sigma }^{*},\mathcal{I}^{\sigma *}_{2})$(Iσ∗,I2σ∗)-convergence, regularly$(\mathcal{I}_{\sigma },\mathcal{I}^{\sigma }_{2} )$(Iσ,I2σ)-Cauchy double sequence, regularly$(\mathcal{I}_{\sigma }^{*},\mathcal{I}^{\sigma *}_{2})$(Iσ∗,I2σ∗)-Cauchy double sequence and investigate the relationship among them.
Effects of morbidity on smoking cessation: a national smoking cessation program
Authors: Seo Young-Gyun , Jo Min-Woo , Paek Yu-Jin , Choi Jaekyung
Published: July 2021

Background

In smokers with chronic diseases, we examined the abstinence rates over 6 months and its affecting factors in the context of the Korea National Health Insurance Service (NHIS) smoking cessation program.

Methods

To identify 6-month abstinence, we extracted a sample of 15,017 participants using the multi-stage stratified cluster sampling method from the 359,047 individuals enrolled in the 2016 NHIS smoking cessation program and 1500 smokers responded to the telephone survey. From this group, 1245 individuals (48.50 ± 12.55 years; men 89.8%) were enrolled, as they had no missing information for confounding variables. We compared chronic disease distribution between participants and current smokers in the 2016 Korea National Health and Nutrition Examination Survey. We evaluated the factors affecting continuous abstinence rate (CAR) across patients with different chronic diseases: hypertension, diabetes mellitus (DM), dyslipidemia (DL), chronic obstructive pulmonary disease, and major depressive disorder (MDD).

Results

While participation of DM patients was high, the participation of DL patients was relatively low. The CAR over 6 months was 44.74%. The adjusted odds ratio (OR) for continuous abstinence over 6 months was significantly lower in the MDD group than in the no-MDD group (OR 0.43, 95% confidence interval [CI] 0.21 to 0.85). The factors of program completion (complete versus incomplete: OR 3.11, 95% CI 2.43 to 3.98), region (non-metropolitan areas versus Seoul metropolitan area: OR 1.28, 95% CI 1.01 to 1.61), and nicotine dependence (severe versus light or moderate: OR 0.64, 95% CI 0.50 to 0.83) were significantly associated with CAR.

Conclusions

The smoking cessation program was not actively recruiting smokers with chronic diseases. The CARs in each disease group were not different from those in the non-disease groups, except that the MDD group had a lower CAR over 6 months than the no-MDD group. Recruiting smokers with chronic diseases and improving their CARs depends on the careful identification of their characteristics.
Economic performance of agritourism: an analysis of farms located in a less favoured area in Italy
Authors: Arru Brunella , Furesi Roberto , Madau Fabio A. , Pulina Pietro
Published: July 2021

Farms that operate in less favoured areas (LFAs) often suffer in achieving adequate profits. Diversification strategies, such as direct selling and offering recreational services, can play an important role in integrating earning sources and, as a consequence, increasing farm profitability. Such opportunities would depend on the efficient distribution and use of farm resources among different activities as well as the added value creation of farm output. However, achieving positive results is not obvious in LFAs due to different types of inherent constraints (geographical, social, economic). The paper aims to evaluate the role of agritourism in affecting the economic performance of multifunctional farms located in a less favoured area of Sardinia (Italy). To be more precise, using so-called working farm income as the main indicator resulting from balance sheet analysis, production factor rewards are determined for 15 agritourism farms. The results show controversial performance but basically highlight the difficulty agritourist farmers have both remunerating their work at market price levels and being profitable. This research contributes to the debate on LFAs and offers useful reflections for policy-makers and practitioners about the potential and critical aspects of agritourism in LFAs.
Nowcasting earthquakes in Sulawesi Island, Indonesia
Authors: Pasari Sumanta , Simanjuntak Andrean V. H. , Neha  , Sharma Yogendra
Published: July 2021

Large devastating events such as earthquakes often display frequency–magnitude statistics that exhibit power-law distribution. In this study, we implement a recently developed method called earthquake nowcasting (Rundle et al. in Earth Space Sci 3: 480–486, 2016) to evaluate the current state of earthquake hazards in the seismic prone Sulawesi province, Indonesia. The nowcasting technique considers statistical behavior of small event counts between successive large earthquakes, known as natural times, to infer the seismic progression of large earthquake cycles in a defined region. To develop natural-time statistics in the Sulawesi Island, we employ four probability models, namely exponential, exponentiated exponential, gamma, and Weibull distribution. Statistical inference of natural times reveals that (i) exponential distribution has the best representation to the observed data; (ii) estimated nowcast scores (%) corresponding to M ≥ 6.5 events for 21 cities are Bau-bau (41), Bitung (70), Bone (44), Buton (39), Donggala (63), Gorontalo (49), Kendari (27), Kolaka (30), Luwuk (56), Makassar (52), Mamuju (58), Manado (70), Morowali (37), Palopo (34), Palu (62), Pare-pare (82), Polewali (61), Poso (42), Taliabu (55), Toli-toli (58), and Watampone (55); and (iii) the results are broadly stable against the changes of magnitude threshold and area of local regions. The presently revealed stationary Poissonian nature of the underlying natural-time statistics in Sulawesi brings out a key conclusion that the seismic risk is the same for all city regions despite their different levels of cycle progression realized through nowcast scores. In addition, though the earthquake potential scores of the city regions will be updated with the occurrence of each small earthquake in the respective region, the seismic risk remains the same throughout the Sulawesi Island.