bluuebunny/crossref_metadata_2025_split huggingface dataset:
The differences between insulin glargine U300 and insulin degludec U100 in impact on the glycaemic variability, arterial stiffness and the lipid profiles in insulin naïve patients suffering from type two diabetes mellitus – outcomes from cross‐over open-label randomized trial
Authors: Cindro Pavle Vrebalov , Krnić Mladen , Modun Darko , Smajić Božo , Vuković Jonatan 
Published: April 2021

Abstract
Background and aims
Diabetes mellitus type two is one of the major cardiovascular risk factors. Treatment of diabetes can reduce this risk, but the treatment options differ a lot in their risk-reducing capabilities. We compared the impact of insulin degludec (IDeg-100) and insulin glargine U300 (IGlar-300) on cardiovascular risk parameters - glycaemic variability (GV), arterial stiffness and lipid parameters - in insulin naive patients with DMT2.

Methods
To 23 individuals who previously had uncontrolled DMT2 on two or more oral antidiabetic drugs, IGlar-300 and IDeg-100 were applied for 12 weeks and then switched in a cross over design manner. Prior and after of each insulin phase, we analysed biochemical parameters,7-point SMBG profile over three days and arterial stiffness which was assessed indirectly by measuring the augmentation index (AIx) on the principles of applanation tonometry.

Results
There were no significant differences between IGlar-300 and IDeg-100 regarding reduction of mean glucose values and coefficient of variation (CV). Both insulins insignificantly reduced AIx for standardised pulse of 75 beats/min and without differences between them. IGlar-300 and IDeg-100 reduced triglycerides and increased HDL with no significant difference between the two insulins. IGlar-300 increased the total cholesterol level and IDeg-100 decreased total cholesterol, but without statistically significant difference. IGlar-300 increased LDL level by 0.508 mmol/L and IDeg-100 decreased LDL by 0.217 mmol/L, with statistically significant difference (p = 0.0215).

Conclusions
This study did not show significant difference between IGlar-300 and IDeg-100 regarding glycaemic parameters and augmentation index using the same dose of 0.2 IU/kg for both insulins, but it has revealed possible differences in impact on lipid profile.

Trial Registration
Clinicaltrials.gov, NCT04692415. Retrospectively registered on December 31th 2020.
Mechanisms of PhotoBioModulation (PBM) focused on oral mucositis prevention and treatment: a scoping review
Authors: Courtois Elodie , Bouleftour Wafa , Guy Jean-Baptiste , Louati Safa , Bensadoun René-Jean , Rodriguez-Lafrasse Claire , Magné Nicolas 
Published: April 2021

AbstractBackgroundOral mucositis (OM) is a severe complication cancer patients undergo when treated with chemoradiotherapy. Photobiomodulation (PBM) therapy also known as low-level laser therapy has been increasingly used for the treatment of such oral toxicity. The aim of this review is to discuss the mechanisms of photobiomodulation (PBM) regarding OM prevention and treatment, and more precisely to focus on the effect of PBM on tumor and healthy cells.MethodsMEDLINE/PubMed, and google scholar were searched electronically. Selected studies were focusing on PBM effects on tumor and healthy cells.ResultsPBM interactions with the tissue and additional mechanism in OM therapy were detailed in this review. Moreover, this review highlighted a controversy about the carcinogenic effect of PBM. Indeed, Many studies reported that PBM could enhance malignant cell proliferation; suggesting that PBM would have no protective effect. In addition to acting on cancer cells, PBM may damage healthy cells.ConclusionMore prospective studies are needed to assess the effect of PBM on cancer cells in order to improve its use for OM prevention and treatment.
Cohort analysis of the state of female genital cutting in Nigeria: prevalence, daughter circumcision and attitude towards its discontinuation
Authors: Gbadebo Babatunde M. , Salawu Adetokunbo T. , Afolabi Rotimi F. , Salawu Mobolaji M. , Fagbamigbe Adeniyi F. , Adebowale Ayo S. 
Published: April 2021

Abstract
Background
Female genital cutting (FGC) inflicts life-long injuries on women and their female children. It constitutes a violation of women’s fundamental human rights and threats to bodily integrity. Though decreasing, the practice is high and widespread in Nigeria despite efforts towards its eradication. This study was conducted to perform cohort analysis of the state of FGC between the years 2009 and 2018 in Nigeria.

Results
The study found that that FGC has reduced over the years from 56.3% among the 1959–1963 birth cohort to 25.5% among 1994–1998 cohorts but a rise in FGC between 1994–1998 cohorts and 1999–2003 cohorts (28.4%). The percentage of respondents who circumcised their daughters reduced from 40.1% among the oldest birth cohort to 3.6% among the younger cohort. Birth-cohort, religion, education, residence, region, and ethnicity were associated with FGC. Factors associated with the daughter’s circumcision were birth-cohort, religion, residence, region, ethnicity, wealth, marital status, FGC status of the respondent, and FGC required by religion. Similar factors were found for discontinuation intention.

Conclusions
The practice of FGC is still high but decreasing among younger birth-cohorts in Nigeria. There is no significant change in the perception of the discontinuation of FGC. More awareness about the adverse effects of FGC, particularly among women with poor education in Nigeria will greatly reduce this cultural menace’s timely eradication.
Exploring how differently patients and clinical tutors see the same consultation: building evidence for inclusion of real patient feedback in medical education
Authors: Barr Jennifer , Ogden Kathryn , Robertson Iain , Martin Jenepher 
Published: April 2021

Abstract
Background
Undergraduate medical education recognises that patient feedback is potentially valuable for student learning and development as a component of multi-source feedback. However greater exploration of how patient feedback perspectives differ to clinical educators is required for curriculum development and improving student feedback literacy. This study aimed to determine how two sources of feedback, patients and clinical tutors, compare on the same patient-centred, interpersonal criteria.

Methods
A patient feedback instrument designed for the undergraduate medical education setting was used to compare patients’ feedback with clinical tutors’ feedback following a student-patient consultation in the learning context. Assessments from 222 learning consultations involving 40 medical students were collected. Descriptive statistics for tutors and patients for each question were calculated and correlations between patient and tutor were explored using Spearman’s rank-order correlation. Mixed effects ordered logistic regression was used to compare each question with an overall rating for tutor and patients in addition to comparing patient with tutor ratings.

Results
Clinical tutor and patient assessments had a weak but significant positive correlation in all areas except questions related to respect and concern. When making judgements compared with overall assessment, patients’ ratings of respect, concern, communication and being understood in the consultation have a greater effect. After eliminating the effect of generally higher ratings by patients compared with tutors using comparative ordered logistic regression, patients rated students relatively less competent in areas of personal interaction.

Conclusion
This study provides insight about patient feedback, which is required to continue improving the use and acceptability of this multisource feedback to students as a valuable component of their social learning environment. We have revealed the different perspective-specific judgement that patients bring to feedback. This finding contributes to building respect for patient feedback through greater understanding of the elements of consultations for which patients can discriminate performance.
Assessing the functionality of an emergency obstetric referral system and continuum of care among public healthcare facilities in a low resource setting: an application of process mapping approach
Authors: Ofosu Bernice , Ofori Dan , Ntumy Michael , Asah-Opoku Kwaku , Boafor Theodore 
Published: April 2021

Abstract
Background
Weak referral systems remain a major concern influencing timely access to the appropriate level of care during obstetric emergencies, particularly for Low-and Middle-Income Countries, including Ghana. It is a serious factor threatening the achievement of the maternal health Sustainable Development Goal. The objective of this study is to establish process details of emergency obstetric referral systems across different levels of public healthcare facilities to deepen understanding of systemic barriers and preliminary solutions in an urban district, using Ablekuma in Accra, Ghana as a case study.

Methods
The study is an analytical cross-sectional study. Nine [1] targeted interviews were carried out for a three-week period in June and July 2019 after informed written consent with two [2] Obstetrics & Gynaecology consultants, two [2] Residents, one family physician, and four [3] Midwives managing emergency obstetric referral across different levels of facilities. Purposeful sampling technique was used to collect data that included a narration of the referral process, and challenges experienced with each step. Qualitative data was transcribed, coded by topics and thematically analysed. Transcribed narratives were used to draft a process map and analyze the defects within the emergency obstetric referral system.

Results
Out of the 34 main activities in the referral process within the facilities, the study identified that 24 (70%) had a range of barriers in relation to communication, transport system, resources (space, equipment and physical structures), staffing (numbers and attitude), Healthcare providers (HCP) knowledge and compliance to referral policy and guideline, and financing for referral. These findings have implication on delay in accessing care. HCP suggested that strengthening communication and coordination, reviewing referral policy, training of all stakeholders and provision of essential resources would be beneficial.

Conclusion
Our findings clearly establish that the emergency obstetric referral system between a typical teaching hospital in an urban district of Accra-Ghana and peripheral referral facilities, is functioning far below optimum levels. This suggests that the formulation and implementation of policies should be focused around structural and process improvement interventions, strengthening collaborations, communication and transport along the referral pathway. These suggestions are likely to ensure that women receive timely and quality care.
Mathematical modeling of intraplaque neovascularization and hemorrhage in a carotid atherosclerotic plaque
Authors: Cai Yan , Pan Jichao , Li Zhiyong 
Published: April 2021

Abstract
Background
Growing experimental evidence has identified neovascularization from the adventitial vasa vasorum and induced intraplaque hemorrhage (IPH) as critical indicators during the development of vulnerable atherosclerotic plaques. In this study, we propose a mathematical model incorporating intraplaque angiogenesis and hemodynamic calculation of the microcirculation, to obtain the quantitative evaluation of the influences of intraplaque neovascularization and hemorrhage on vulnerable plaque development. A two-dimensional nine-point model of angiogenic microvasculature is generated based on the histology of a patient’s carotid plaque. The intraplaque angiogenesis model includes three key cells (endothelial cells, smooth muscle cells, and macrophages) and three key chemical factors (vascular endothelial growth factors, extracellular matrix, and matrix metalloproteinase), which densities and concentrations are described by a series of reaction–diffusion equations. The hemodynamic calculation by coupling the intravascular blood flow, the extravascular plasma flow, and the transvascular transport is carried out on the generated angiogenic microvessel network. We then define the IPH area by using the plasma concentration in the interstitial tissue, as well as the extravascular transport across the capillary wall.

Results
The simulational results reproduce a series of pathophysiological phenomena during the atherosclerotic plaque progression. It is found that the high microvessel density region at the shoulder areas and the extravascular flow across the leaky wall of the neovasculature contribute to the IPH observed widely in vulnerable plaques. The simulational results are validated by both the in vivo MR imaging data and in vitro experimental observations and show significant consistency in quantity ground. Moreover, the sensitivity analysis of model parameters reveals that the IPH area and extent can be reduced significantly by decreasing the MVD and the wall permeability of the neovasculature.

Conclusions
The current quantitative model could help us to better understand the roles of microvascular and intraplaque hemorrhage during the carotid plaque progression.
A heparin–rosuvastatin-loaded P(LLA-CL) nanofiber-covered stent inhibits inflammatory smooth-muscle cell viability to reduce in-stent stenosis and thrombosis
Authors: Liu Yingjun , Liu Peixi , Song Yaying , Li Sichen , Shi Yuan , Quan Kai , Yu Guo , Li Peiliang , An Qingzhu , Zhu Wei 
Published: April 2021

Abstract
Background
An endovascular covered-stent has unique advantages in treating complex intracranial aneurysms; however, in-stent stenosis and late thrombosis have become the main factors affecting the efficacy of covered-stent treatment. Smooth-muscle-cell phenotypic modulation plays an important role in late in-stent stenosis and thrombosis. Here, we determined the efficacy of using covered stents loaded with drugs to inhibit smooth-muscle-cell phenotypic modulation and potentially lower the incidence of long-term complications.

Methods
Nanofiber-covered stents were prepared using coaxial electrospinning, with the core solution prepared with 15% heparin and 20 µM rosuvastatin solution (400: 100 µL), and the shell solution prepared with 120 mg/mL hexafluoroisopropanol. We established a rabbit carotid-artery aneurysm model, which was treated with covered stents. Angiography and histology were performed to evaluate the therapeutic efficacy and incidence rate of in-stent stenosis and thrombosis. Phenotype, function, and inflammatory factors of smooth-muscle cells were studied to explore the mechanism of rosuvastatin action in smooth-muscle cells.

Result
Heparin–rosuvastatin-loaded nanofiber scaffold mats inhibited the proliferation of synthetic smooth-muscle cells, and the nanofiber-covered stent effectively treated aneurysms in the absence of notable in-stent stenosis. Additionally, in vitro experiments showed that rosuvastatin inhibited the smooth-muscle-cell phenotypic modulation of platelet-derived growth factor-BB induction and decreased synthetic smooth-muscle-cell viability, as well as secretion of inflammatory cytokines.

Conclusion
Rosuvastatin inhibited the abnormal proliferation of synthetic smooth-muscle cells, and heparin–rosuvastatin-loaded covered stents reduced the incidence of stenosis and late thrombosis, thereby improving the healing rates of stents used for aneurysm treatment.

Graphic abstract
Inhibition of CPT1a as a prognostic marker can synergistically enhance the antileukemic activity of ABT199
Authors: Mao Shihui , Ling Qing , Pan Jiajia , Li Fenglin , Huang Shujuan , Ye Wenle , Wei Wenwen , Lin Xiangjie , Qian Yu , Wang Yungui , Huang Xin , Huang Jiansong , Wang Jinghan , Jin Jie 
Published: April 2021

Abstract
Background
Fatty acid oxidation (FAO) provides an important source of energy to promote the growth of leukemia cells. Carnitine palmitoyltransferase 1a(CPT1a), a rate-limiting enzyme of the essential step of FAO, can facilitate cancer metabolic adaptation. Previous reports demonstrated that CPT1a acts as a potential molecular target in solid tumors and hematologic disease. However, no systematic study was conducted to explore the prognostic value of CPT1a expression and possible treatment strategies with CPT1a inhibitor on acute myeloid leukemia (AML).

Methods
The expression of CPT1a in 325 cytogenetically normal AML (CN-AML) patients was evaluated using RT-PCR. The combination effects of ST1326 and ABT199 were studied in AML cells and primary patients. MTS was used to measure the cell proliferation rate. Annexin V/propidium iodide staining and flow cytometry analysis was used to measure the apoptosis rate. Western blot was used to measure the expression of Mcl-1. RNAseq and GC-TOFMS were used for genomic and metabolic analysis.

Results
In this study, we found AML patients with high CPT1a expression (n = 245) had a relatively short overall survival (P = 0.01) compared to patients in low expression group (n = 80). In parallel, downregulation of CPT1a inhibits proliferation of AML cells. We also conducted genomic and metabolic interactive analysis in AML patients, and found several essential genes and pathways related to aberrant expression of CPT1a. Moreover, we found downregulation of CPT1a sentitized BCL-2 inhibitor ABT199 and CPT1a-selective inhibitor ST1326 combined with ABT199 had a strong synergistic effect to induce apoptosis in AML cells and primary patient blasts for the first time. The underlying synergistic mechanism might be that ST1326 inhibits pGSK3β and pERK expression, leading to downregulation of Mcl-1.

Conclusion
Our study indicates that overexpression of CPT1a predicts poor clinical outcome in AML. CPT1a-selective inhibitor ST1326 combined with Bcl-2 inhibitor ABT199 showed strong synergistic inhibitory effects on AML.
Perceptions, attitudes, and knowledge of teachers serving as mental health lay counselors in a low and middle income country: a mixed methods pragmatic pilot study
Authors: Cruz Christina M. , Lamb Molly M. , Giri Priscilla , Vanderburg Juliana , Ferrarone Peter , Bhattarai Surekha , Giardina Aileen A. , Hampanda Karen , Gaynes Bradley N. , Matergia Michael 
Published: April 2021

Abstract
Background
Low and middle-income countries (LMICs) lack trained child mental health professionals. While teachers’ child development experience potentially positions them to fill the gap as lay mental health counselors, they have rarely delivered indicated child mental health care in LMICs. As part of assessing the feasibility of teachers serving as lay counselors, we explored teachers’ perceptions of serving as lay counselors and their mental health attitudes and knowledge.

Methods
In 2018, with training and supervision, 19 primary school teachers from five rural, low cost private schools in Darjeeling, India, served as lay counselors in their classrooms. Using mixed methods, we examined teacher perceptions of serving as lay counselor and mental health attitudes and knowledge through a survey (n = 15), a summative assessment (n = 14), and semi-structured interviews (n = 17). For the survey and summative assessment, pre-training, post-training, and post-intervention mean scores were compared using paired t tests. Post-intervention interviews were coded for teachers’ perceptions of serving as lay counselor and mental health attitudes and knowledge.

Results
Qualitatively, teachers expressed being willing to serve as lay counselor, having more inclusive mental health attitudes, and retaining mental health knowledge as applicable to use during instructional time or incorporation into the knowledge transfer process, their primary duty. By contrast, quantitatively, teachers’ attitudes appeared to become more inclusive on the study-specific survey pre versus post-training, but reverted to pre-training levels post-intervention. Teachers’ mental health knowledge on the summative assessment did not change pre-training versus post-training versus post-intervention.

Conclusions
Training, supervision, and serving as lay counselors led to teachers’ willingness to serve as lay counselors. Teachers served as lay counselors by utilizing therapeutic techniques during class time and incorporating them into their typical instruction, not through delivering traditional office-like care. Teacher practices may be pointing to the potential emergence of an “education as mental health therapy” system of care. Their changes in attitudes and knowledge reflected their emerging practices. Quantitative measures of knowledge and attitude changes did not capture these nuanced changes.
Trial Registration The parent feasibility trial was registered on January 01, 2018 with Clinical Trials Registry – India (CTRI), reg. no. CTRI/2018/01/011471, ref. no. REF/2017/11/015895. http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=21129&EncHid=&modid=&compid=%27,%2721129det%27..
SARS-CoV-2 interacts with platelets and megakaryocytes via ACE2-independent mechanism
Authors: Shen Shu , Zhang Jingyuan , Fang Yaohui , Lu Sihong , Wu Jun , Zheng Xin , Deng Fei 
Published: April 2021

AbstractEvidence suggests that platelets may directly interact with SARS-CoV-2, raising the concern whether ACE2 receptor plays a role in this interaction. The current study showed that SARS-CoV-2 interacts with both platelets and megakaryocytes despite the limited efficiency. Abundance of the conventional receptor ACE2 and alternative receptors or co-factors for SARS-CoV-2 entry was characterized in platelets from COVID-19 patients and healthy persons as well as human megakaryocytes based on laboratory tests or previously reported RNA-seq data. The results suggest that SARS-CoV-2 interacts with platelets and megakaryocytes via ACE2-independent mechanism and may regulate alternative receptor expression associated with COVID-19 coagulation dysfunction.
nPhase: an accurate and contiguous phasing method for polyploids
Authors: Abou Saada Omar , Tsouris Andreas , Eberlein Chris , Friedrich Anne , Schacherer Joseph 
Published: April 2021

AbstractWhile genome sequencing and assembly are now routine, we do not have a full, precise picture of polyploid genomes. No existing polyploid phasing method provides accurate and contiguous haplotype predictions. We developed nPhase, a ploidy agnostic tool that leverages long reads and accurate short reads to solve alignment-based phasing for samples of unspecified ploidy (https://github.com/OmarOakheart/nPhase). nPhase is validated by tests on simulated and real polyploids. nPhase obtains on average over 95% accuracy and a contiguous 1.25 haplotigs per haplotype to cover more than 90% of each chromosome (heterozygosity rate ≥ 0.5%). nPhase allows population genomics and hybrid studies of polyploids.