bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors for pharmacological therapy and perinatal outcomes with metformin treatment in women with gestational diabetes
Authors: Brzozowska Malgorzata M. , Puvanendran Anita , Bliuc Dana , Zuschmann Andrew , Piotrowicz Agata K. , O’Sullivan Anthony 
Published: January 2023

BackgroundThe prevalence of gestational diabetes mellitus (GDM) has been increasing in Australia and worldwide. The study aims were to examine, in comparison with dietary intervention, perinatal outcomes for women with gestational diabetes who were attending a single hospital clinic and to identify predictors for their pharmacological GDM treatment.MethodsA prospective, observational study of women with GDM, treated with “Diet, N= 50”, “Metformin, N = 35”, “Metformin and Insulin, N = 46” or “Insulin, N = 20”.FindingsThe mean BMI for the whole cohort was 25.8 ± 4.7 kg/m2. The Metformin group, compared to the Diet group, had OR=3.1 (95% CI:1.13 to 8.25) for caesarean section birth (LSCS) compared to normal vaginal birth mode with no longer such a significant association after controlling for the number of their elective LSCS. The insulin treated group had the highest number of small for gestational age neonates (20%, p&lt;0.05) with neonatal hypoglycaemia (25%, p&lt; 0.05). Fasting glucose value on oral GTT (glucose tolerance test) was the strongest predictor for a pharmacological intervention requirement with OR = 2.77 (95CI%: 1.16 to 6.61), followed by timing of OGTT with OR=0.90 (95% CI: 0.83 to 0.97) and previous pregnancy loss with OR=0.28 (95% CI:0.10 to 0.74).InterpretationThese data suggest that metformin may be a safe alternative treatment to insulin treatment in GDM. Raised fasting glucose on oral GTT was the strongest indicator that GDM women with BMI &lt; 35 kg/m2 may require pharmacological therapy. Further studies are needed to identify the most effective and safe management of gestational diabetes within the public hospital setting.Australian New Zealand Clinical Trial Registry ANZCTR Trial IdACTRN12620000397910.
Modelling a tradable transport permit scheme using system dynamics
Authors: Harrison Gillian , Shepherd Simon 
Published: January 2023

Introduction: In this paper we consider system dynamics (SD) modelling of tradable transport permit schemes (TTPS). TTPS are complex and uncertain, having not yet been implemented beyond experimental trials anywhere in the world, yet have for some time been suggested as an efficient and equitable policy response to reducing car-based travel and its associated externalities.Method: Although there is a large number of econometric models that explore the potential of TTPS, there have been none published (to our knowledge) that have used the SD approach. SD is an appropriate method for developing our understanding of TTPS efficiency and equity as it captures feedbacks and tracks the influence of the TTPS over a period of time. Thus, we have developed an SD model of TTPS, drawing from the literature that already exists. It is a micro-level model that considers heterogeneity within a population on a daily basis over a matter of months. We carry out sensitivity testing of price sensitivity, initial permit price, daily preference and permit allocation and develop combined scenarios of these attributes.Results: Our modelling results suggest a sensitivity of TTPS to heterogeneity across the population, which will influence the final equilibrium price. Trading encourages a redistribution of wealth across the population but may also mean that some travel needs are not met, which may require some allocation according to need or a certain portion of protected permits. The inclusion of non-car users within the allocation further encourages trading behaviours and allows for compensation for externalities of car use.Discussion: Through an analysis of outputs we are able to bring new insights into the governance frameworks required for a successful TTPS. In particular we have shown the importance of allocation considerations in the design of a TTPS when issues of fairness across the population are considered. Although there is no data of existing schemes available for us to calibrate our models, we compare the trends with data from an in-the-field TTPS experiment.
Effect of Ca doping on the arbitrary canting of magnetic exchange interactions in La1-xCaxMnO3 nanoparticles
Authors: Ali Akhtar , Shah Wiqar H. , Safeen Akif , Ali Liaqat , Tufail Muhammad , Ullah Zakir , Safeen Kashif , Eldin Sayed M. , R. Ali Mohamed , Sohail Muhammad , Imran Naveed 
Published: January 2023

La1-xCaxMnO3 nanoparticles (x = 0.1, 0.2, 0.3) (LCMO NPs) were synthesized using the coprecipitation method. The prepared samples were investigated using x-ray diffraction (XRD), which confirmed the single-phase structure. The nanoparticle’s crystallite size was determined using Debye–Scherrer’s formula. Scanning electron microscopy showed that the size of the nanoparticles was between 33 nm and 55 nm. Energy-dispersive x-ray spectroscopy (EDX) was used to determine the elemental composition of samples. The four-probe method was used to measure the temperature-dependent electrical resistivity. Magnetic properties, such as hysteresis loop, magnetoresistance, and magnetization versus temperature, were measured using a vibrating sample magnetometer. The study of magnetization versus applied magnetic field M(H) showed that, at 77 K, all the loops exhibit ferromagnetism. DC magnetization versus temperature at a 70-Oe-applied field for all samples showed a paramagnetic-ferromagnetic phase transition. A decrease in Curie temperature Tc after increasing the concentration of x was observed. The real and imaginary parts of temperature-dependent ac magnetic susceptibility were measured and revealed a transition from the ferromagnetic to the paramagnetic phase at a particular temperature Tc, with DC magnetization behavior.
The domestication of the African Union model law on medical products regulation: Perceived benefits, enabling factors, and challenges
Authors: Ncube Bakani Mark , Dube Admire , Ward Kim 
Published: January 2023

IntroductionIn 2016, the African Union (AU) Model Law on Medical Products Regulation was endorsed by AU Heads of State and Government. The aims of the legislation include harmonisation of regulatory systems, increasing collaboration across countries, and providing a conducive regulatory environment for medical product/health technology development and scale-up. A target was set to have at least 25 African countries domesticating the model law by 2020. However, this target has not yet been met. This research aimed to apply the Consolidated Framework for Implementation Research (CFIR) in analysing the rationale, perceived benefits, enabling factors, and challenges of AU Model Law domestication and implementation by AU Member States.MethodsThis study was a qualitative, cross-sectional, census survey of the national medicines regulatory authorities (NRAs) of Anglophone and Francophone AU Member States. The heads of NRAs and a senior competent person were contacted to complete self-administered questionnaires.ResultsThe perceived benefits of model law implementation include enabling the establishment of an NRA, improving NRA governance and decision-making autonomy, strengthening the institutional framework, having streamlined activities which attract support from donors, as well as enabling harmonisation, reliance, and mutual recognition mechanisms. The factors enabling domestication and implementation are the presence of political will, leadership, and advocates, facilitators, or champions for the cause. Additionally, participation in regulatory harmonisation initiatives and the desire to have legal provisions at the national level that allow for regional harmonisation and international collaboration are enabling factors. The challenges encountered in the process of domesticating and implementing the model law are the lack of human and financial resources, competing priorities at the national level, overlapping roles of government institutions, and the process of amending/repealing laws being slow and lengthy.ConclusionThis study has enabled an improved understanding of the AU Model Law process, the perceived benefits of its domestication, and the enabling factors for its adoption from the perspective of African NRAs. NRAs have also highlighted the challenges encountered in the process. Addressing these challenges will result in a harmonised legal environment for medicines regulation in Africa and be an important enabler for the effective operation of the African Medicines Agency.
New protocol for kinetic assay seeding ability recovery “KASAR” from formalin-fixed paraffin-embedded tissues
Authors: Hepker Monica , Clabaugh Griffin , Jin Huajun , Kanthasamy Anumantha G. 
Published: January 2023

The real-time quaking-induced conversion (RT-QuIC) alpha-synuclein (aSyn) protein kinetic seeding assay has been very useful for detecting pathological aggregates in various synucleinopathies including Parkinson’s disease (PD). This biomarker assay relies on fresh frozen tissue to effectively seed and amplify aSyn aggregating protein. With vast repositories of formalin-fixed paraffin-embedded (FFPE) tissues, it is paramount to harness the power of kinetic assays to unlock the diagnostic potential of archived FFPE biospecimens. However, the major challenge posed by significantly reduced amplification of formalin-fixed tissues in the assay suggests that formalin fixation deterred monomer interaction with the sample seed and depressed subsequent protein aggregation. To overcome this challenge, we developed a kinetic assay seeding ability recovery (KASAR) protocol to maintain the integrity of the tissue and seeding protein. For this, we implemented a series of heating steps with the brain tissue suspended in a buffer composed of 500 mM tris-HCl (pH 7.5) and 0.02% SDS after the standard deparaffinization of the tissue sections. Initially, samples from seven human brain samples, including four samples from patients diagnosed with dementia with Lewy bodies (DLB) and three samples from healthy controls without DLB, were compared to fresh frozen samples under three different, but clinically common sample storage conditions: formalin-fixed, FFPE, and FFPE slices cut 5 µm thick. The KASAR protocol was able to recover seeding activity for all positive samples in all storage conditions. Next, 28 FFPE samples from the submandibular gland (SMG) of patients diagnosed with PD, incidental Lewy body disease (ILBD), or healthy controls were tested with 93% of results replicating when blinded. With samples of only a few milligrams, this protocol recovered the same quality of seeding in formalin-fixed tissue as fresh frozen tissue. Moving forward, protein aggregate kinetic assays, in conjunction with the KASAR protocol, can be used to understand and diagnose neurodegenerative diseases more comprehensively. Overall, our KASAR protocol unlocks and restores the seeding ability of formalin-fixed paraffin-embedded tissues for the amplification of biomarker protein aggregates in kinetic assays.
Endothelial cell TRPA1 activity exacerbates cerebral hemorrhage during severe hypertension
Authors: Sullivan Michelle N. , Thakore Pratish , Krishnan Vivek , Alphonsa Sushma , Li Wencheng , Feng Earley Yumei , Earley Scott 
Published: January 2023

Introduction: Hypoxia-induced dilation of cerebral arteries orchestrated by Ca2+-permeable transient receptor potential ankyrin 1 (TRPA1) cation channels on endothelial cells is neuroprotective during ischemic stroke, but it is unknown if the channel has a similar impact during hemorrhagic stroke. TRPA1 channels are endogenously activated by lipid peroxide metabolites generated by reactive oxygen species (ROS). Uncontrolled hypertension, a primary risk factor for the development of hemorrhagic stroke, is associated with increased ROS production and oxidative stress. Therefore, we hypothesized that TRPA1 channel activity is increased during hemorrhagic stroke.Methods: Severe, chronic hypertension was induced in control (Trpa1fl/fl) and endothelial cell-specific TRPA1 knockout (Trpa1-ecKO) mice using a combination of chronic angiotensin II administration, a high-salt diet, and the addition of a nitric oxide synthase inhibitor to drinking water. Blood pressure was measured in awake, freely-moving mice using surgically placed radiotelemetry transmitters. TRPA1-dependent cerebral artery dilation was evaluated with pressure myography, and expression of TRPA1 and NADPH oxidase (NOX) isoforms in arteries from both groups was determined using PCR and Western blotting techniques. In addition, ROS generation capacity was evaluated using a lucigenin assay. Histology was performed to examine intracerebral hemorrhage lesion size and location.Results: All animals became hypertensive, and a majority developed intracerebral hemorrhages or died of unknown causes. Baseline blood pressure and responses to the hypertensive stimulus did not differ between groups. Expression of TRPA1 in cerebral arteries from control mice was not altered after 28 days of treatment, but expression of three NOX isoforms and the capacity for ROS generation was increased in hypertensive animals. NOX-dependent activation of TRPA1 channels dilated cerebral arteries from hypertensive animals to a greater extent compared with controls. The number of intracerebral hemorrhage lesions in hypertensive animals did not differ between control and Trpa1-ecKO animals but were significantly smaller in Trpa1-ecKO mice. Morbidity and mortality did not differ between groups.Discussion: We conclude that endothelial cell TRPA1 channel activity increases cerebral blood flow during hypertension resulting in increased extravasation of blood during intracerebral hemorrhage events; however, this effect does not impact overall survival. Our data suggest that blocking TRPA1 channels may not be helpful for treating hypertension-associated hemorrhagic stroke in a clinical setting.
Thoracic dorsal root ganglion stimulation reduces acute myocardial ischemia induced ventricular arrhythmias
Authors: Kuwabara Yuki , Howard-Quijano Kimberly , Salavatian Siamak , Yamaguchi Tomoki , Saba Samir , Mahajan Aman 
Published: January 2023

BackgroundDorsal root ganglion stimulation (DRGS) may serve as a novel neuromodulation strategy to reduce cardiac sympathoexcitation and ventricular excitability.ObjectiveIn this pre-clinical study, we investigated the effectiveness of DRGS on reducing ventricular arrhythmias and modulating cardiac sympathetic hyperactivity caused by myocardial ischemia.MethodsTwenty-three Yorkshire pigs were randomized to two groups, which was control LAD ischemia-reperfusion (CONTROL) or LAD ischemia-reperfusion + DRGS (DRGS) group. In the DRGS group (n = 10), high-frequency stimulation (1 kHz) at the second thoracic level (T2) was initiated 30 min before ischemia and continued throughout 1 h of ischemia and 2 h of reperfusion. Cardiac electrophysiological mapping and Ventricular Arrhythmia Score (VAS) were assessed, along with evaluation of cFos expression and apoptosis in the T2 spinal cord and DRG.ResultsDRGS decreased the magnitude of activation recovery interval (ARI) shortening in the ischemic region (CONTROL: −201 ± 9.8 ms, DRGS: −170 ± 9.4 ms, p = 0.0373) and decreased global dispersion of repolarization (DOR) at 30 min of myocardial ischemia (CONTROL: 9546 ± 763 ms2, DRGS: 6491 ± 636 ms2, p = 0.0076). DRGS also decreased ventricular arrhythmias (VAS–CONTROL: 8.9 ± 1.1, DRGS: 6.3 ± 1.0, p = 0.038). Immunohistochemistry studies showed that DRGS decreased % cFos with NeuN expression in the T2 spinal cord (p = 0.048) and the number of apoptotic cells in the DRG (p = 0.0084).ConclusionDRGS reduced the burden of myocardial ischemia-induced cardiac sympathoexcitation and has a potential to be a novel treatment option to reduce arrhythmogenesis.
Outcomes and prognostic factors in initially unresectable hepatocellular carcinoma treated using conversion therapy with lenvatinib and TACE plus PD-1 inhibitors
Authors: Li Xingzhi , Chen Jie , Wang Xiaobo , Bai Tao , Lu Shaolong , Wei Tao , Tang Zhihong , Huang Chengwen , Zhang Bin , Liu Bowen , Li Lequn , Wu Feixiang 
Published: January 2023

PurposeTo evaluate the outcomes and prognostic factors for patients using conversion therapy with lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus programmed cell death protein-1 (PD-1) inhibitors (LTP) for initially unresectable hepatocellular carcinoma (iuHCC).MethodsData on 94 consecutive patients with iuHCC who received LTP conversion therapy from November 2019 to September 2022 were retrospectively analyzed. Early tumor response was reported when patients showed complete or partial response at the time of their first follow-up (4–6 weeks) after initial treatment, in accordance with mRECIST. The endpoints consisted of conversion surgery rate, overall survival (OS), and progression-free survival (PFS).ResultsEarly tumor response was found in 68 patients (72.3%) and not in the remaining 26 patients (27.7%) in the entire cohort. Early responders had a significantly higher conversion surgery rate than non-early responders (44.1% vs. 7.7%, p=0.001). Early tumor response was the only factor independently associated with successful conversion resection, as indicated by multivariate analysis (OR=10.296; 95% CI: 2.076–51.063; p=0.004). Survival analysis showed that early responders had longer PFS (15.4 vs. 7.8 months, p=0.005) and OS (23.1 vs. 12.5 months, p=0.004) than non-early responders. Early responders who underwent conversion surgery also had significantly longer median PFS and OS (not reached, not reached) than those who did not (11.2 months, p=0.004; 19.4 months, p&lt;0.001). In multivariate analyses, early tumor response was identified as an independent prognostic factor for longer OS (HR=0.404, 95% CI: 0.171–0.954; p=0.039). Successful conversion surgery was also an independent predictive factor for longer PFS (HR=0.248, 95% CI: 0.099–0.622; p=0.003) and OS (HR=0.147, 95% CI: 0.039–0.554; p=0.005).ConclusionsEarly tumor response is an important predictive marker for successful conversion surgery and prolonged survival in patients with iuHCC treated using LTP conversion therapy. Conversion surgery is necessary to improve survival during conversion therapy, particularly for early responders.
Childhood vaccination practices and associated factors among mothers/caregivers in Debre Tabor town, Northwest Ethiopia: A cross-sectional study
Authors: Simegn Wudneh , Diress Mengistie , Gela Yibeltal Yismaw , Belay Daniel Gashaneh , Ayelign Kibret Anteneh , Chilot Dagmawi , Sinamaw Deresse , Abdu Seid Mohammed , Andualem Amare Agmas , Anmut Bitew Desalegn , Eshetu Habitu Birhan , Mohammed Seid Abdulwase 
Published: January 2023

BackgroundIncomplete immunization and non-immunization increase the risk of disease and death among children. This study aims to assess childhood vaccination practices and associated factors among mothers and caregivers in Debre Tabor town, Amhara region, Ethiopia.MethodsA community-based cross-sectional study design was conducted between February 30 and April 30, 2022. The study participants were proportionally allocated to all six kebeles found in the town. A systematic random sampling technique was used to select the study participants. The collected data were checked and coded and then entered into EpiData Version 3.1 and exported into SPSS Version 26. The results were organized using frequency tables, graphs, and charts, and bivariate and multivariable logistic regression were used to test the association of covariates with childhood vaccination practices.ResultApproximately 422 study mothers and caregivers participated in the study, with a response rate of 100%. The mean age was 30.63 years (11.74), which ranged from 18 to 58 years. More than half of the study participants (56.4%) expressed fears about the side effects of vaccination. A majority (78.4%) of the study participants availed of counseling services about vaccination, and 71.1% of them received regular antenatal care. This study found that approximately 280 [66.4%, 95% confidence interval (CI): 61.8–70.6] mothers/caregivers had a history of good childhood vaccination practices. The factors of the fear of side effects [adjusted odds ratio (AOR) = 3.34; 95% CI: 1.72–6.49], no workload (AOR = 6.08; 95% CI: 1.74–21.22), medium workload (AOR = 4.80; 95% CI: 1.57–14.71), being a mother of child/children (AOR = 2.55; 95% CI: 1.27–5.13), positive attitude (AOR = 2.25; 95% CI: 1.32–3.82), and sound knowledge (AOR = 3.88; 95% CI: 2.26–6.68) were significantly associated with childhood vaccination practices.ConclusionMore than half of the study participants had a history of good childhood vaccination practices. However, the rate of such practices was low among mothers and caregivers. The fear of side effects, workload, motherhood, attitude, and knowledge were all factors associated with childhood vaccination practices. Awareness creation and a consideration of the workload of mothers would be helpful in dispelling fears and increasing the rate of good practices among mothers and caregivers.
Association between vitamin A and asthma: A meta-analysis with trial sequential analysis
Authors: Hu Jun , Sang Jiajia , Hao Feng , Liu Li 
Published: January 2023

Objective: To explore the association between vitamin A (vit A) status and risk of asthma.Methods: PubMed, Web of Science, Embase and the Cochrane Library were electronically searched to identify related studies that reported the association between vit A status and asthma. All databases were searched from inception to November 2022. Two reviewers independently screened literature, extracted data, and assessed risk bias of included studies. Meta-analysis was performed on R software Version 4.1.2 and STATA Version 12.0.Results: A total of 19 observational studies were included. A pooled analysis showed that the serum vit A concentrations in patients with asthma was lower than that in healthy controls (standard mean difference (SMD)= −2.479, 95% confidence interval (CI): −3.719, −.239, 95% prediction interval (PI): −7.510, 2.552), and relatively higher vit A intake in pregnancy was associated with an increased risk of asthma at age 7 years (risk ratio (RR)= 1.181, 95% CI: 1.048, 1.331). No significant correlation was observed between serum vit A levels or vit A intake and the risk of asthma.Conclusion: Our meta-analysis confirms that serum vit A levels are lower in patients with asthma than in healthy controls. Relatively higher vit A intake during pregnancy is associated with an increased risk of asthma at age 7 years. There is no significant correlation between vit A intake and asthma risk in children, nor between serum vit A levels and asthma risk. The effect of vit A may depend on age or developmental stage, diet and genetics. Therefore, further studies are needed to explore the association of vit A and asthma.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/CRD42022358930, identifier CRD42022358930