bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrospun poly (L-lactic acid)/gelatine membranes loaded with doxorubicin for effective suppression of glioblastoma cell growthin vitroandin vivo
Authors: Liu Boxun , Jin Zhizhong , Chen Haiyan , Liang Lun , Li Yao , Wang Guo , Zhang Jing , Xu Tao 
Published: July 2021

AbstractElectrospun membranes are attracting interest as a drug delivery system because of their material composition flexibility and versatile drug loading. In this study, the electrospun membrane was loaded with doxorubicin (DOX) via electrostatic adsorption for long-term drug delivery. DOX loading process was optimized by varying temperature, time, drug concentration, pH and ionic strength of solutions. The loading process did not impair the structural properties of the membrane. Next, we investigated the drug release kinetics using spectroscopic techniques. The composite membranes released 22% of the adsorbed DOX over the first 48 h, followed by a slower and sustained release over 4 weeks. The DOX release was sensitive to acidic solutions that the release rate at pH 6.0 was 1.27 times as that at pH 7.4. The DOX-loaded membranes were found to be cytotoxic to U-87 MG cells in vitro that decreased the cell viability from 82.92% to 25.49% from 24 to 72 h of co-incubation. These membranes showed strong efficacy in suppressing tumour growth in vivo in glioblastoma-bearing mice that decreased the tumour volume by 77.33% compared with blank membrane-treated group on Day 20. In conclusion, we have developed an effective approach to load DOX within a clinically approved poly (L-lactic acid)/gelatine membrane for local and long-term delivery of DOX for the treatment of glioblastoma.
Gelatin methacrylate hydrogel scaffold carrying resveratrol-loaded solid lipid nanoparticles for enhancement of osteogenic differentiation of BMSCs and effective bone regeneration
Authors: Wei Bangguo , Wang Wenrui , Liu Xiangyu , Xu Chenxi , Wang Yanan , Wang Ziqi , Xu Jinnuo , Guan Jianzhong , Zhou Pinghui , Mao Yingji 
Published: July 2021

AbstractCritical-sized bone defects caused by traumatic fractures, tumour resection and congenital malformation are unlikely to heal spontaneously. Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts. In this study, we developed an innovative bone engineering scaffold based on gelatin methacrylate (GelMA) hydrogel, obtained via a two-step procedure: first, solid lipid nanoparticles (SLNs) were loaded with resveratrol (Res), a drug that can promote osteogenic differentiation and bone formation; these particles were then encapsulated at different concentrations (0.01%, 0.02%, 0.04% and 0.08%) in GelMA to obtain the final Res-SLNs/GelMA scaffolds. The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration in rat cranial defects were evaluated using various characterization assays. Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs, with the ideally slow and steady release of Res; the optimal scaffold was 0.02 Res-SLNs/GelMA. Therefore, the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility, osteoconduction and osteoinduction, thereby showing potential for application in bone tissue engineering.
Canakinumab in systemic juvenile idiopathic arthritis: real-world data from a retrospective Italian cohort
Authors: De Matteis Arianna , Bracaglia Claudia , Pires Marafon Denise , Piscitelli Anna Lucia , Alessio Maria , Naddei Roberta , Orlando Francesca , Filocamo Giovanni , Minoia Francesca , Ravelli Angelo , Tibaldi Jessica , Cimaz Rolando , Marino Achille , Simonini Gabriele , Mastrolia Maria Vincenza , La Torre Francesco , Tricarico Ilaria , Licciardi Francesco , Montin Davide , Maggio Maria Cristina , Alizzi Clotilde , Martini Giorgia , Civino Adele , Gallizzi Romina , Olivieri Alma Nunzia , Ardenti Morini Francesca , Conti Giovanni , De Benedetti Fabrizio , Pardeo Manuela 
Published: July 2021

Abstract

Objective
The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA).

Methods
A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months.

Results
A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 [odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006] and between non-response and history of MAS [OR 3.53 (95% CI: 1.06, 11.70), P = 0.039]. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years.

Conclusion
We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.
Loneliness Loves Company, Some More than Others: Social Ties, Form of Engagement, and Their Relation to Loneliness
Authors: Rinderknecht R Gordon , Doan Long , Sayer Liana C 
Published: July 2021

Abstract
Although tie strength is a significant theoretical concept in the field, recent work suggests that other dimensions of social ties may be important to consider. We build on this body of work to propose that situational forms of engagement with various interaction partners play a vital role in shaping feelings of loneliness. We anticipate that when engaging in direct forms of engagement (active engagement), the association between different types of social ties and loneliness will be minimal. In contrast, while engaging in less direct forms of engagement (passive engagement), the type of social tie may matter more in reducing loneliness. We test these expectations using original time-diary data capturing daily interactions and momentary feelings of loneliness. Results show that active engagement associates with reduced feelings of loneliness relative to passive engagement. We find that the benefit of active engagement over passive engagement is greatest among acquaintances and family members. We interpret this as indicating that active engagement is beneficial for establishing a sense of connection among some social ties that already exists for other social ties. These findings indicate that how we engage with others and the kinds of people we engage with jointly shape the benefits of social interaction.
Concurrent central nervous system involvement in immunocompetent adults with pulmonary miliary TB: a prospective analysis
Authors: Urs Vijeth L , Rizvi Imran , Kumar Neeraj , Garg Ravindra Kumar , Srivastava Anand , Garg Rajiv , Jain Amita , Parihar Anit , Verma Rajesh , Sharma Praveen , Uniyal Ravi , Pandey Shweta , Malhotra Hardeep Singh 
Published: July 2021

Abstract

Background
Wallgren's tuberculosis (TB) timetable demonstrated co-occurrence of miliary TB and tuberculous meningitis in children. To verify the same in immunocompetent adults, we prospectively evaluated the prevalence and spectrum of central nervous system (CNS) involvement in patients with pulmonary miliary TB.

Materials and Methods
This was a tertiary care, University hospital-based, prospective evaluation performed from December 2018 to June 2020. Newly diagnosed patients with pulmonary miliary TB were subjected to a detailed clinical, laboratory and MRI-based evaluation. All patients received treatment as per WHO guidelines.

Results
Out of 342 patients with pulmonary TB, 53 patients met the eligibility criteria. The median age at presentation was 32 y and approximately two-thirds of patients were female. Clinically, only two-fifths of patients had features of CNS involvement. Cerebrospinal fluid (CSF) and imaging abnormalities were noted in 46 patients each. Twelve (23.5%) patients were diagnosed with definite-category tuberculous meningitis. Presence of an infarct significantly correlated with neurological features. Mantoux positivity correlated significantly with the presence of choroid tubercles, CSF changes and brain tuberculomas.

Conclusion
This is the first study to endorse Wallgren's observations in immunocompetent adults. A high index of suspicion, even in asymptomatic patients, may uncover tuberculous lesions involving the CNS and guide optimal monitoring of patients.
Working at Home
Authors: Graham Melissa , Weale Victoria , Lambert Katrina A. , Kinsman Natasha , Stuckey Rwth , Oakman Jodi 
Published: July 2021

Objective:
To examine the impact of working at home on general health, pain, stress, and work-family and family-work conflict, and differences based on gender and parental responsibilities.

Methods:
A convenience sample of 658 adults completed an online questionnaire. Regression modeling examined the effects and interactions of gender and parental responsibility on general health, musculoskeletal discomfort/pain frequency and severity, stress, and work-family and family-work conflict.

Results:
Women reported more pain and discomfort, regardless of the presence of children, than men with children. Women with children experienced increased stress compared with men with children. Women without children experienced less work-family conflict, and those without children experienced less family-work conflict than men with children.

Conclusions:
The impact on pain, stress, and work-family and family-work conflict, due to mandated working at home, is gendered and influenced by parental responsibilities.
Stakeholders’ perception of possible integration pathways for eye health into school health programme in Zanzibar: a qualitative health system research
Authors: Chan Ving Fai , Yard Elodie , Mashayo Eden , Mulewa Damaris , Drake Lesley , Omar Fatma 
Published: July 2021

AbstractPurposeTo scope the potential for eye health programme to be integrated into Zanzibar School Health programme, through the lenses of stakeholdersMethodsEmbedded into an operational research project integrating eye and School health, we elicited responses from 83 participants, purposefully selected from the Ministry of Health (n=7), Ministry of Education and Vocational Training (n=7), hospitals/eye centres (n=5), master trainers (4) and schools (n=60) participated in in-depth interviews. Their responses were analysed and grouped into four pre-determined themes of Human Resource Training, Resources Mobilisation, Acceptability, and Leadership and Governance. Quotations are presented to illustrate the findings.ResultsIn line with the four research themes, i) The integrated school eye health programme training was satisfactory, with room for improvement, ii) Child eye health screening conducted by teachers was well-received, with concerns and suggestions to improve its effectiveness and efficiency, iii) Integration of eye health into the school health programme is perceived as a good initiative, but to increase referral, service uptake and spectacle usage, primary care units must be equipped, and eye health awareness needs to be improved, iv) Departmental roles, resources, gaps and synergies to ensure eye health is successfully integrated into the school health programme.ConclusionThe concept of integrated school eye health delivery is generally well-received by beneficiaries and stakeholders within an operational research project in Zanzibar, with the caveat that investment is required for effective referral and update.
Statistical Analysis Plan for the Helmet Non-Invasive Ventilation for COVID-19 Patients (Helmet-COVID) Randomized Controlled Trial
Authors: Arabi Yaseen , Tlayjeh Haytham , Aldekhyl Sara , Al-Dorzi Hasan , Abdukahil Sheryl Ann , Jose Jesna , Al Harbi Mohammad Khulaif , Haji Husain Al , Mutairi Mohammed Al , Zumai Omar Al , Qasim Eman Al , Wehaibi Wedyan Al , Qahtani Saad Al , Alshahrani Mohammed , Albrahim Talal , Mady Ahmed , Bshabshe Ali Al , Aseri Zohair Al , Duhailib Zainab Al , Kharaba Ayman , Alqahtani Rakan , Algethamy Haifa , Alfaris Omar , Alnafel Omar , Al-Fares Abdulrahman A 
Published: July 2021

AbstractBackground and objectiveNoninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation having multiple advantages over other support modalities but data about effectiveness are limited.MethodsIn this multicenter randomized trial of helmet non-invasive ventilation for COVID-19 patients (Helmet-COVID), 320 adult ICU patients with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (with a ratio of arterial oxygen partial pressure to fraction (percent) of inspired oxygen (PaO2/FiO2) <200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate >10 L/min or above) will be randomized to helmet-noninvasive ventilation with usual care or usual care alone. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction from 40% to 25%.ConclusionConsistent with international guidelines, we developed a detailed plan to guide the analysis of the Helmet-COVID trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes to facilitate unbiased analyses of clinical data.Trial registrationClinicaltrials.gov: NCT04477668 (registered on July 20, 2020)
The final blink: intact eyeblink conditioning in isolated dystonia
Authors: Sadnicka Anna , Rocchi Lorenzo , Latorre Anna , Antelmi Elena , Teo James , Pareés Isabel , Hoffland Britt S , Brock Kristian , Kornysheva Katja , Edwards Mark J , Bhatia Kailash P , Rothwell John C 
Published: July 2021

Structured AbstractBackgroundImpaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia yet the results from individual studies are conflicting and underpowered.ObjectiveTo systematically examine the influence of dystonia, dystonia subtype and clinical features over eyeblink conditioning within a statistical model which controlled for the covariates age and sex.MethodsOriginal neurophysiological data from all published studies were shared to an age and sex matched control group. Two raters blinded to participant identity scored all recordings (6732 trials). After higher inter-rater agreement was confirmed, mean conditioning per block was entered into a mixed repetitive measures model.ResultsMuch variability of eyeblink conditioning was seen in both groups. All dystonia versus controls showed no difference in conditioning (p=0.517). Analysis of dystonia subgroup, with age and sex as covariates did not reveal evidence that eyeblink conditioning is impaired in specific subtypes (cervical dystonia, DYT-TOR1A, DYT-THAP1 or focal hand dystonia). The presence of tremor did not significantly influence levels of eyeblink conditioning.ConclusionsCollaborative efforts such as this article allow larger number of patients to be evaluated and provide more balanced estimates of disease effects over experimental outcomes. Intact eyeblink conditioning is against a global cerebellar learning deficit in isolated dystonia. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains an open research question.
Assessment of knowledge, attitude, and practices of Tuberculosis patients towards DOTs regimen in Jimma Health Center, Jimma zone, southwest Ethiopia
Authors: Amare Wudalem , Teshome Melese Sinaga , Dessie Gashaw , Malik Tabarak 
Published: July 2021

AbstractObjectiveGlobally, tuberculosis (TB) is one of a chronic infectious disease, which has a major health burden. Thus, 9.4 million incidents and 14 million prevalent cases were reported in 2010. The high burden of TB is common in sub-Saharan Africa countries, including Ethiopia. The purpose of conducting this study was to assess the knowledge, attitude, and practices of TB patients towards DOTs regimen. The other objective of the study was to assess the attitude of patients towards causative factor and its treatment.ResultsThe result of the study showed that 103 (68.7%) of patients scored high knowledge status, whereas 47 (31.3%) of them scored low. 25(16.7%) governmental employee had overall high knowledge status. 101 (67.3%) of the patient scored high overall attitude, while 49 (32.7%) of them scored low overall attitude. 85 (56.7%) of patients scored high overall practices, whereas 65(43.3%) of them scored low overall practices.In this study, the knowledge and attitude of patients about TB and its treatment was found within low level of perception. Therefore, implementation of health education and awareness creation are required to avoid the problem of patients.
Development of a High-Performance Multiparametric MRI Oropharyngeal Primary Tumor Auto-Segmentation Deep Learning Model and Investigation of Input Channel Effects: Results from a Prospective Imaging Registry
Authors: Wahid Kareem A. , Ahmed Sara , He Renjie , van Dijk Lisanne V. , Teuwen Jonas , McDonald Brigid A. , Salama Vivian , Mohamed Abdallah S.R. , Salzillo Travis , Dede Cem , Taku Nicolette , Lai Stephen Y. , Fuller Clifton D. , Naser Mohamed A. 
Published: July 2021

AbstractBackground and PurposeOropharyngeal cancer (OPC) primary gross tumor volume (GTVp) segmentation is crucial for radiotherapy. Multiparametric MRI (mpMRI) is increasingly used for OPC adaptive radiotherapy but relies on manual segmentation. Therefore, we constructed mpMRI deep learning (DL) OPC GTVp auto-segmentation models and determined the impact of input channels on segmentation performance.Materials and MethodsGTVp ground truth segmentations were manually generated for 30 OPC patients from a clinical trial. We evaluated five mpMRI input channels (T2, T1, ADC, Ktrans, Ve). 3D Residual U-net models were developed and assessed using leave-one-out cross-validation. A baseline T2 model was compared to mpMRI models (T2+T1, T2+ADC, T2+Ktrans, T2+Ve, all 5 channels [ALL]) primarily using the Dice similarity coefficient (DSC). Sensitivity, positive predictive value, Hausdorff distance (HD), false-negative DSC (FND), false-positive DSC, surface DSC, 95% HD, and mean surface distance were also assessed. For the best model, ground truth and DL-generated segmentations were compared through a Turing test using physician observers.ResultsModels yielded mean DSCs from 0.71 (ALL) to 0.73 (T2+T1). Compared to the T2 model, performance was significantly improved for HD, FND, sensitivity, surface DSC, and 95% HD for the T2+T1 model (p<0.05) and for FND for the T2+Ve and ALL models (p<0.05). There were no differences between ground truth and DL-generated segmentations for all observers (p>0.05).ConclusionDL using mpMRI provides high-quality segmentations of OPC GTVp. Incorporating additional mpMRI channels may increase the performance of certain evaluation metrics. This pilot study is a promising step towards fully automated MR-guided OPC radiotherapy.
Purifying selection determines the short-term time dependency of evolutionary rates in SARS-CoV-2 and pH1N1 influenza
Authors: Ghafari Mahan , du Plessis Louis , Raghwani Jayna , Bhatt Samir , Xu Bo , Pybus Oliver G , Katzourakis Aris 
Published: July 2021

AbstractHigh throughput sequencing enables rapid genome sequencing during infectious disease outbreaks and provides an opportunity to quantify the evolutionary dynamics of pathogens in near real-time. One difficulty of undertaking evolutionary analyses over short timescales is the dependency of the inferred evolutionary parameters on the timespan of observation. Here, we characterise the molecular evolutionary dynamics of SARS-CoV-2 and 2009 pandemic H1N1 (pH1N1) influenza during the first 12 months of their respective pandemics. We use Bayesian phylogenetic methods to estimate the dates of emergence, evolutionary rates, and growth rates of SARS-CoV-2 and pH1N1 over time and investigate how varying sampling window and dataset sizes affects the accuracy of parameter estimation. We further use a generalised McDonald-Kreitman test to estimate the number of segregating non-neutral sites over time. We find that the inferred evolutionary parameters for both pandemics are time-dependent, and that the inferred rates of SARS-CoV-2 and pH1N1 decline by ∼50% and ∼100%, respectively, over the course of one year. After at least 4 months since the start of sequence sampling, inferred growth rates and emergence dates remain relatively stable and can be inferred reliably using a logistic growth coalescent model. We show that the time-dependency of the mean substitution rate is due to elevated substitution rates at terminal branches which are 2-4 times higher than those of internal branches for both viruses. The elevated rate at terminal branches is strongly correlated with an increasing number of segregating non-neutral sites, demonstrating the role of purifying selection in generating the time-dependency of evolutionary parameters during pandemics.
Genetic influences on the intrinsic and extrinsic functional organizations of the cerebral cortex
Authors: Zhao Bingxin , Li Tengfei , Smith Stephen M. , Fan Zirui , Yang Xiaochen , Yang Yilin , Shu Juan , Xiong Di , Wang Xifeng , Yang Yue , Luo Tianyou , Zhu Ziliang , Shan Yue , Li Yujue , Wu Zhenyi , Zhang Heping , Li Yun , Stein Jason L. , Zhu Hongtu 
Published: July 2021

AbstractThe human cerebral cortex is a vital component of brain function, but the genetic influences on cortical functional organization remain poorly understood. In this study, we used a parcellation-based approach to process resting-state and task-evoked functional magnetic resonance imaging (fMRI) from over 48,000 individuals in UK Biobank and ABCD studies. We identified 47 loci associated with functional areas and networks at rest, 15 of which also affected functional connectivity during task performance. We observed patterns of heritability and locus-specific genetic effects across different brain functional areas and networks. Our findings suggest that specific functional areas and networks share genetic influences with cognition, mental health, and major brain disorders such as Alzheimer’s disease and schizophrenia. For example, theAPOEε4 locus strongly associated with Alzheimer’s disease was particularly associated with the visual cortex in the secondary visual and default mode networks in both resting and task fMRI. This study contributes to our understanding of the genetic determinants of cerebral cortex function by analyzing biobank-scale fMRI data in high-resolution brain parcellation. Additionally, it prioritizes genetically associated fMRI traits for specific brain disorders.
COVID-19 in Londrina-PR-Brazil: SEIR Model with Parameter Optimization
Authors: Cirilo Eliandro R. , Natti Paulo L. , Romeiro Neyva M. L. , Godoi Pedro H. V. , Lerma Andina A. , Matias Vitor P. 
Published: July 2021

AbstractThe first cases of COVID-19 in Londrina-PR were manifested in March 2020 and the disease lasts until the present moment. We aim to inform citizens in a scientific way about how the disease spreads. The present work seeks to describe the behavior of the disease over time. We started from a compartmental model of ordinary differential equations like SEIR to find relevant information such as: transmission rates and prediction of the peak of infected people. We used the data released by city hall of Londrina to carry out simulations in periods of 14 days, applying a parameter optimization technique to obtain results with the greatest possible credibility.