bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted inhibition of PPARα ameliorates CLA‐induced hypercholesterolemia via hepatic cholesterol biosynthesis reprogramming
Authors: Liu Hao‐Yu , Hu Ping , Li Yanwei , Sun Ming‐An , Qu Huan , Zong Qiufang , Gu Haotian , Chen Xiaobo , Bao Wenbin , Cai Demin
Published: February 2022

Background & Aims

Disruption of lipid metabolism is largely linked to metabolic disorders, such as hypercholesterolemia (HCL) and liver steatosis. While cholesterol metabolic re‐programmers can serve as targets for relevant interventions. Here we explored the dietary conjugated linoleic acids (CLA)‐induced HCL in mice and the molecular regulation behind it.

Methods

A high dose of CLA supplementation in the diet was used to induce HCL in mice and was found to cause a hyper‐activated cholesterol biosynthesis programme in the liver, leading to cholesterol metabolism dysregulation. The effects of a small‐molecule drug targeting PPARα, i.e., GW6471 were studied in vivo in mice fed diets with CLA supplementation for 28 days, and in primary hepatocytes derived from HCL‐mice in vitro.

Results

We demonstrate that CLA induced HCL and liver steatosis through multiple pathways. Among which was the PPARα‐mediated cholesterogenesis. It was found to cooperate with SREBP2 via binding to Hmgcr and Dhcr7 (genes encoding key enzymes of the cholesterol biosynthetic pathway) and recruits the histone marks H3K27ac and H3K4me1 and cofactors. PPARα inhibition disrupts its physical association with SREBP2 by blocking cobinding of PPARα and SREBP2 to the genomic DNA response element. We showed that NR RORγ functions as an essential mediator that facilitates the interaction of PPARα and SREBP2 to modulate the cholesterol biosynthesis genes expression.

Conclusions

Our study unravels that the small‐molecule compound GW6471 exerts an attractive therapeutic effect for CLA‐induced HCL, involving multiple pathways with the “PPARα‐RORγ‐SREBP2” being a potential complex player in this hepatic cholesterol biosynthesis programming.
Extrahepatic manifestations of progressive familial intrahepatic cholestasis syndromes: Presentation of a case series and literature review
Authors: Pfister Eva‐Doreen , Dröge Carola , Liebe Roman , Stalke Amelie , Buhl Nicole , Ballauff Antje , Cantz Tobias , Bueltmann Eva , Stindt Jan , Luedde Tom , Baumann Ulrich , Keitel Verena
Published: February 2022

Background and Aims

Progressive familial intrahepatic cholestasis (PFIC) is a collective term for a heterogenous group of rare, inherited cholestasis syndromes. The number of genes underlying the clinical PFIC phenotype is still increasing. While progressive liver disease and its sequelae such as portal hypertension, pruritus and hepatocellular carcinoma determine transplant‐free survival, extrahepatic manifestations may cause relevant morbidity.

Methods

We performed a literature search for extrahepatic manifestations of PFIC associated with pathogenic gene variants in ATP8B1, ABCB11, ABCB4, TJP2, NR1H4 and MYO5B. To illustrate the extrahepatic symptoms described in the literature, PFIC cases from our centres were revisited.

Results

Extrahepatic symptoms are common in PFIC subtypes, where the affected gene is expressed at high levels in other tissues. While most liver‐associated complications resolve after successful orthotopic liver transplantation (OLT), some extrahepatic symptoms show no response or even worsen after OLT.

Conclusion

The spectrum of extrahepatic manifestations in PFIC highlights essential, non‐redundant roles of the affected genes in other organs. Extrahepatic features contribute towards low health‐related quality of life (HRQOL) and morbidity in PFIC. While OLT is often the only remaining, curative treatment, potential extrahepatic manifestations need to be carefully monitored and addressed.
A hybrid spatial–temporal deep learning architecture for lane detection
Authors: Dong Yongqi , Patil Sandeep , van Arem Bart , Farah Haneen
Published: February 2022

Accurate and reliable lane detection is vital for the safe performance of lane‐keeping assistance and lane departure warning systems. However, under certain challenging circumstances, it is difficult to get satisfactory performance in accurately detecting the lanes from one single image as mostly done in current literature. Since lane markings are continuous lines, the lanes that are difficult to be accurately detected in the current single image can potentially be better deduced if information from previous frames is incorporated. This study proposes a novel hybrid spatial–temporal (ST) sequence‐to‐one deep learning architecture. This architecture makes full use of the ST information in multiple continuous image frames to detect the lane markings in the very last frame. Specifically, the hybrid model integrates the following aspects: (a) the single image feature extraction module equipped with the spatial convolutional neural network; (b) the ST feature integration module constructed by ST recurrent neural network; (c) the encoder–decoder structure, which makes this image segmentation problem work in an end‐to‐end supervised learning format. Extensive experiments reveal that the proposed model architecture can effectively handle challenging driving scenes and outperforms available state‐of‐the‐art methods.
Renewable and non‐renewable energy resources of Pakistan and their applicability under the current scenario in Pakistan
Authors: Asif Muhammad , Salman Muhammad Umar , Anwar Saqaina , Gul Maryam , Aslam Reema
Published: February 2022

Energy is a basic need for human development but unfortunately, every country in the world has unequal energy reserves. The energy crisis is the most influential crisis for the World and especially Pakistan to affect the economic, social and environmental health of the society. The purpose of this study is to investigate the connection between the different energy sources for the cost, yield, and other parametres. Using very comprehensive and statistical data, this study shows that renewable energy from agricultural waste and nuclear energy may be the most welcomed source of energy, which is cheaper and enough for thousands of years. As a renewable source, bio‐energy obtained from agricultural waste is environmentally friendly. The Environmental pollution by agricultural waste energy was found to be very lower than nuclear energy to meet the domestic as well as industrial‐level energy production and consumption.
Effects of soil treatments and tree species on reforestation of well pads
Authors: Van Dyke Fred , Wilderman Susan , Harju Seth , Faulkner Janay , Hindy Kirsten , Kitzel Patrick , Marshall Taylor , Redick Caleb , Rowley Dave , Tolsma Joseph , Vander Stelt Victoria , Wolfe Anna M. , Keas Brian , Witters‐Hicks Kynan
Published: February 2022

Anthropogenically induced arrested succession is a global problem in forest ecosystems. In northern Michigan (U.S.A.), oil development has arrested succession in forest landscapes since the 1970s and oil well pads have not reforested up to 30 years after being vacated. To explore pathways for reforestation, we evaluated survivorship and growth of northern red oak (Quercus rubra), white oak (Q. alba), jack pine (Pinus banksiana), and red pine (P. resinosa) at monthly intervals during growing seasons from 2015 to 2019 on pads, which had been vacated 9–34 years prior to the initiation of our study. We planted trees in four soil surface treatments—experimental control (planting only, no treatment), disking, fertilization, and disking with fertilization. While monitoring survivorship and growth of planted trees, we concurrently examined natural reforestation in untreated control areas on each pad and differences between soil characteristics of pads and surrounding forests. Pinus resinosa displayed highest overall survivorship regardless of treatment, but maximum survivorship in disked soils and experimental control areas. Other species had highest survivorship in disked soils. There was no significant reforestation in untreated control areas during the 5‐year study period. Pads had higher levels of Bray P, Ca, and Mg, but lower levels of Fe, organic matter, and moisture than forest soils. Concentrations of toxic chemicals associated with drilling activities were not different between pad and forest soils or, if different, within acceptable levels for plant growth. In reforesting well pads, restorationists should plant P. resinosa in disked soil to achieve highest tree survivorship and density.
Pre‐eruption magma staging at the long‐lived intraplate Dunedin Volcano, New Zealand
Authors: Baxter Rachael J. M. , White James D. L. , Brenna Marco , Ohneiser Christian
Published: February 2022

The oldest‐known rocks of the eroded Dunedin Volcano (DV), New Zealand, active 16.0–11.0 Ma, were emplaced by penecontemporaneous explosive eruptions and intrusions of magmas with a remarkable range of compositions, including basanite, alkali basalt, trachyte and phonolite. The compositional diversity of magmas emplaced in rapid succession during the earliest development of the volcano signify the existence of a complex magmatic system and highly evolved magmas, typical of those attributed to mature magmatic systems; here it developed in concert with the volcano's surface eruptions. We infer that multiple deep and shallow reservoirs were suddenly tapped as volcanism commenced. DV repeatedly erupted the same range of magmas over 5 Myr, suggests that these distributed reservoirs failed to significantly integrate through millions of years of slow volcano growth.
In situ U–Pb geochronology of Pre‐Salt carbonates reveals links between diagenesis and regional tectonics
Authors: Rochelle‐Bates Nathan , Wood Rachel , Schröder Stefan , Roberts Nick M. W.
Published: February 2022

Identification of processes driving carbonate diagenesis requires an accurate chronology, particularly along volcanic margins where complex mineral parageneses develop. The Cretaceous “Pre‐Salt” carbonates formed in the volcanic proto‐South Atlantic and are now extensive hydrocarbon reservoirs offshore Brazil and Angola. Primary and diagenetic textures strongly affect reservoir properties, but timings of deposition (c. Barremian–early Aptian) and diagenesis are poorly constrained. This study provides the first direct age measurements from offshore Pre‐Salt carbonates using in situ U–Pb geochronology. Depositional calcites from the Santos Basin (Brazil) do not preserve depositional ages, instead yielding an Albian recrystallization age of 106.9 ± 4.3 Ma. Dolomite rhombs and bridges have Palaeocene ages of 59.2 ± 5.3 Ma, and 58.0 ± 4.6 Ma, respectively. Calcite recrystallization was linked to the onset of oceanic spreading in the South Atlantic. Contrary to existing models, dolomites formed much later, during a time of enhanced tectono‐magmatism in southeastern Brazil.
Pleistocene–Holoceneout‐of‐sequence faulting along theMedlicott‐WadiaThrust in theNWHimalaya
Authors: Dey Saptarshi , Thiede Rasmus C. , Chauhan Naveen , Nath Debashis , Schaaf Niklas W. , Jain Vikrant
Published: February 2022

Understanding millennial‐scale fault activity and related structural architecture from seismic gaps in active orogens is important for assessment of future seismic risks. Here, we present new Late Pleistocene–Holocene shortening rates across a segment of the 600‐km‐long Medlicott‐Wadia Thrust (MWT) system in the Sub‐Himalaya (SH) from the far‐western Himalayan sector of Jammu. OSL‐dated offset and folded fluvial strath terraces provide a measure for the intra‐wedge convergence and document strain partitioning within the SH, among which the MWT is the most active. Estimated differential uplift rates across the frontal and rear splay of the MWT is 3.2 ± 0.8 mm/a and 3.1 ± 0.4 which translates into a cumulative Late Pleistocene–Holocene shortening rate of 5.5 ± 0.5–5.8 ± 0.5 mm/a on the MWT. Previously published balanced cross‐sections proposed deformation pattern and in range of ~1 mm/a. Our study reaffirms deformation rates from neighbouring MWT fault segments; moreover, it provides independent constraints to the structural architecture of the frontal fold‐and‐thrust belt and implies changes in fault displacement rates on Quaternary time‐scales.
Rectal screening for azole non‐susceptible Candida species in patients undergoing liver transplantation
Authors: Radcliffe Christopher , Patel Kishan K. , Azar Marwan M. , Koff Alan , Belfield Kristen D. , Peaper David R. , Topal Jeffrey E. , Malinis Maricar
Published: February 2022

Introduction

Candidiasis is the most common invasive fungal infection in solid organ transplant recipients, and liver transplant (LT) recipients are at heightened risk. We hypothesized that pre‐transplant screening for azole non‐susceptible Candida (ANSC) allows for tailored antifungal prophylaxis to reduce the incidence of post‐LT ANSC infection.

Methods

We performed a retrospective chart review of adult (age ≥18 years) patients who underwent LT at Yale New Haven Hospital from April 2019 to March 2021. Screening for ANSC, defined as Candida glabrata or Candida krusei, was performed using a rectal swab prior to or at the time of LT.

Results

During the study period, ANSC screening was performed in 47 patients who underwent a total of 48 LTs, with 46/48 (96%) primary LTs and two re‐transplantations. Ten of 48 screened cases (21%) had ANSC‐positive rectal swabs. Only seven of 10 ANSC‐colonized patients received appropriate antifungal prophylaxis (i.e., anidulafungin), and one of these seven patients developed candidemia within 30 days of LT. The median number of candidiasis risk factors was one, and 29% of the cohort had two or more risk factors.

Discussion

Routine ANSC screening of LT candidates may assist in selecting appropriate antifungal prophylaxis but may be insufficient to prevent infection in those with multiple risk factors for Candida infection
System Usability Survey for Mobile Application for Horse Training Program
Authors: Rosman Amirul Asyraf , Mohd Latip Hadafi Fitri
Published: February 2022

In order to effectively train a horse, it is critical to adopt exercise or training programs that are based on a correct training concept, as this can assist horse riders in having a proper planned training management and therefore developing their horse's performance. Mobile phone applications are so entwined in modern culture and are continuously accessible to users as they could be beneficial as mobile coaching systems. The goal of this research is to employ mobile application software to guide horse riders in conditioning their horses to optimal performance and to emphasize the need of using appropriate and accurate equipment. The theory of app development of the app will be using ADDIE model. The process of creating this mobile app will be undergoing five different phases of Analysis, Design, Development, Implementation and Evaluation. A sample of 40 respondents had been given free access to use and try the mobile application before a System Usability Scale (SUS) test was given. Results from the five positive-preferred SUS components had obtained a range of mean from 4.30 to 4.60, which are very close to the ideal of 5.00. The range of standard deviation also shows better whereby the range are between 0.54948 to 0.91147 which are under common ideal practice which is 1.10. The results obtained show that the users were satisfied and the usability of the mobile application was good, up to 82.5% of the respondents were interested to install the mobile application, and positive feedbacks were also recorded. These results show that people are ready and willing to use the mobile application as an alternative way to an accessible horse exercise options and horse training programs in easier way.
Conceptual Design of a Socially Intelligent Agent with Triadic Empathy and Theory of Mind for Mental Health Support
Authors: Ab Aziz Azizi , Jemili Mohamad Farif
Published: February 2022

For socially intelligent agents to become a fully digital therapist to support individual with mental health problem in the future, they need to know how to socially interact with humans. One of the key ingredients to allow this skill to take place is an ability to exhibit empathic behaviours. Despite a number of socially intelligent agents were build with empathic behaviour, they only cover single empathy behaviour, contrary to more complex triadic empathic behaviours. In this article, the conceptual design and model to implement triadic empathy in socially intelligent agents is presented.
Antibacterial and Cytotoxicity Analyses on Aloe vera Body Soap
Authors: Alex Lo Zhen Kai  , Mohd Daud Nurizzati , Muhamad Zain Norhidayu
Published: February 2022

Aloe vera is a well-known succulent plant and it is often used to moisturise and sooth the skin. In this study, Aloe vera is incorporated into natural soap to investigate the antibacterial properties and cytotoxicity of the samples. The antibacterial properties of the Aloe vera sample was determined by performing zone inhibition and bacterial colony test on Escherichia coli (E. coli). The cell viability test was conducted with human skin fibroblast cells through MTT assay. The Aloe vera samples showed antibacterial properties through the presence of inhibition zones and in the bacterial colony analysis, the Aloe vera samples have inhibitory effect against E. coli with a bacterial retardation percentage of 31.97±0.90%. The cell viability percentage of 95.30±11.16% was found on the Aloe vera sample with normal cell morphology. These results testified that the Aloe vera sample was biocompatible and possessed antibacterial properties which is suitable to be incorporated in skin products.
Review on the Effectiveness of Aromatherapy Oils in the Learning of Autistic Children in an Educational Setting
Authors: Dolah Jasni , Amreek Singh Armeet Kaur Chal , Che Ahmad Aznan , Mustafa Muhizam , Abdul Majid Ahmad Zuhairi , Azraai Nur Zaidi , Mohd Bakhir Norfarizah
Published: February 2022

This review was performed to determine the objective of therapeutic intervention on the learning of autistic children. This literature review aimed at addressing two critical issues: (1) the benefits of aromatherapy oils, including the understanding of its effect on ASD children in literature, and (2) the significance of its effect on their learning. An extensive search was carried out on various online databases, including ERIC, ProQuest Education Journals, and Scopus using the following phrases: (“aromatherapy oils” or “aromatherapy oils in learning”) and (“ASD children”). The studies selected for this review examined therapeutic interventions to improve the learning of autistic children and were analyzed using the content analysis method. Despite appeals for further studies in the 1980 and 1990s, no scientific evidence is available to substantiate the use of aromatherapy oils for learning. Although there are increased studies on aromatherapy oils, the impact on learning, especially for ASD children, has not been investigated. Furthermore, the methodological details on the use of aromatherapy oils in education remain poor. This study demonstrated that traditional methods for treating people with autism are not the only approach and that there is an alternative method using essential oils that is both healthy and toxic-free. The efficiency of basic oil was refuted, and clear evidence of essential oil benefits for people with autism understand was presented. This study would be of great interest to parties including parents of autistic children and organizations that assist people with autism.
Classification of Lung Cancer Stages from CT Scan Images Using Image Processing and k-Nearest Neighbours
Authors: Abdullah Mohd Firdaus , Sulaiman Siti Noraini , Usman Muhammad Khusairi , A. Karim Nor Khairiah , Shuaib Ibrahim Lutfi , Alhamdu Muhamad Daniyal Irfan , Che Ani Adi Izhar
Published: February 2022

Lung cancer is the prevalent cause of death among people around the world. The detection of the existence of lung cancer can be performed in a variety of ways, such as magnetic resonance imaging (MRI), radiography, and computed tomography (CT). Such techniques take up a lot of time and financial resources. Nevertheless, for the detection of lung cancer, CT provides a lower cost, fast imaging time, and increased availability. Early diagnosis of lung cancer may help physicians treat patients to minimize the number of deaths. This paper revolves around the categorization of lung cancer stages from CT scan images using image processing and k-Nearest Neighbor. The central objective of this study is therefore to establish an image processing technique for extracting features of lung cancer from CT scan images. Extracting the features from the segmented image can help to detect cancer inside the lung. The purposed method comprises the following steps by using image processing techniques: data collection, data pre-processing, features selection, and lung cancer classification. The pre-processing was done using a median filter to remove noise contained in the images. Three features need to be extracted which are area, perimeter, and centroid. Finally, the set of data with these features were used as inputs for lung cancer classification. By analysis results, the kNN method has a high accuracy of 98.15%.
Degradation Analysis on Electrospun Membrane of Polyurethane Blended Chitosan for Cardiovascular Graft
Authors: Selvaras Thiviya , Jaganathan Saravana Kumar , Sivalingam Sivakumar , Saidin Syafiqah
Published: February 2022

Coronary heart disease (CHD) is classified as the heart abnormality aside from myocardial damage which results in the blockage of coronary arteries which supply blood to the heart. In this study, a degradable vascular graft was developed to overcome the complications that associated with CHD. The degradable graft was fabricated in a structure of electrospun membranes using polyurethane (PU) matrix blended with chitosan (CS). The degradation analyses were performed through an immersion procedure by conducting the weight loss measurement and the element release test. The blending of PU with CS resulted in the increment of membrane degradability. The CS elements were released from the PU/CS membranes following the Higuchi model release mechanism. As a conclusion, the PU/CS membranes possess the degradable properties which might serve as a plausible candidate for the development of vascular graft for repairing cardiac damage.
Mobile Application for Horse Training Program System
Authors: Rosman Amirul Asyraf , Mohd Latip Hadafi Fitri
Published: February 2022

Different equestrian sports may necessitate distinct training regimens or demands. Inadequate knowledge of appropriate and acceptable horse exercise regimes and training programs may result in horse injury and non-progressive horse performance. It is critical to adopt exercise or training programs that are based on a correct training concept, as this can assist horse riders in having a proper planned training management and therefore developing their horse's performance. Mobile phone applications are so entwined in modern culture and are continuously accessible to users, they could be beneficial as mobile coaching systems targeted at raising physical activity levels. The goal of this research is to employ mobile application software to guide horse riders in conditioning their horses to optimal performance and to emphasize the need of using appropriate and accurate equipment. The theory of development of the app will be using ADDIE model. The mobile application was developed using the online software development tool; Kodular Creator.
Promoting independent living and preventing lonely death in an older adult: Soma Idobata-Nagaya after the 2011 Fukushima disaster
Authors: Ito Naomi , Kinoshita Yuri , Morita Tomohiro , Tsubokura Masaharu
Published: February 2022

Contrary to the assumption that older adults are only cared for by their families in rural Japan, this case illustrates that community formation can effectively provide older adult care after an emergency as well. We look at the life of a woman who lived in a housing facility for older adults, Idobata-Nagaya in Soma, Japan, exploring how social housing—which addresses the needs of older adults regarding community, familiarity and socialising—can provide a viable, effective and comfortable environment for older adults to live. In the case of Idobata-Nagaya, not only could older adults take care of one another but they could also share experiences of the Fukushima disaster with each other. This is a qualitative case study which provides a stable foundation for policymakers, healthcare workers and government officials to better understand the effectiveness of housing projects for communities and older adults in Japan and globally.
Giant cell-rich solitary fibrous tumour of the lacrimal gland with prominent angiomatoid cystic changes and an underlying NAB2ex3-STAT6ex18 fusion
Authors: Alsaadi Khaled A , Alwohaib Manar , Pinto Karen , Ali Rola H
Published: February 2022

Giant cell-rich solitary fibrous tumour (GCR-SFT) is a rare variant of SFT with a predilection for the orbital region. Despite its hypervascularity, extensive angiomatoid cystic changes are unusual in GCR-SFT and may pose a diagnostic challenge. A 47-year-old man presented with a right eye proptosis and a protruding tumour of several years’ duration with recently accelerated tumour growth. MRI revealed a cystic-solid heterogeneous mass arising from the lacrimal gland and displacing the globe. A subtotal excision of the mass was performed due to unanticipated hypervascularity and intraoperative bleeding. Pathologically, a vascular neoplasm was initially suspected. The diagnosis of GCR-SFT was made following careful evaluation and demonstration of CD34 and STAT6 expression. Molecular studies revealed a pathognomonic but rare NAB2ex3-STAT6ex18 fusion variant as well as a TP53 mutation suggestive of aggressive phenotype. The patient had a complete resolution of the proptosis but the clinical picture remains guarded due to incomplete resection.
Mortality attributable to type 2 diabetes mellitus in Latin America and the Caribbean: a comparative risk assessment analysis
Authors: Guzman-Vilca Wilmer Cristobal , Carrillo-Larco Rodrigo M
Published: February 2022

Introduction

We quantified the proportion and the absolute number of deaths attributable to type 2 diabetes mellitus (T2DM) in Latin America and the Caribbean (LAC) using an estimation approach.

Research design and methods

We combined T2DM prevalence estimates from the NCD Risk Factor Collaboration, relative risks between T2DM and all-cause mortality from a meta-analysis of cohorts in LAC, and death rates from the Global Burden of Disease Study 2019. We estimated population-attributable fractions (PAFs) and computed the absolute number of attributable deaths in 1990 and 2019 by multiplying the PAFs by the total deaths in each country, year, sex, and 5-year age group.

Results

Between 1985 and 2014 in LAC, the proportion of all-cause mortality attributable to T2DM increased from 12.2% to 16.9% in men and from 14.5% to 19.3% in women. In 2019, the absolute number of deaths attributable to T2DM was 349 787 in men and 330 414 in women. The highest death rates (deaths per 100 000 people) in 2019 were in Saint Kitts and Nevis (325 in men, 229 in women), Guyana (313 in men, 272 in women), and Haiti (269 in men, 265 in women).

Conclusions

A substantial burden of all deaths is attributed to T2DM in LAC. To decrease the mortality attributable to T2DM in LAC, policies are needed to strengthen early diagnosis and management, along with the prevention of complications.
Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial
Authors: Athalye-Jape Gayatri , Esvaran Meera , Patole Sanjay , Simmer Karen , Nathan Elizabeth , Doherty Dorota , Keil Anthony , Rao Shripada , Chen Liwei , Chandrasekaran Lakshmi , Kok Chooi , Schuster Stephan , Conway Patricia
Published: February 2022

Objective

Evidence indicates that multistrain probiotics benefit preterm infants more than single-strain (SS) probiotics. We assessed the effects of SS versus triple-strain (TS) probiotic supplementation (PS) in extremely preterm (EP) infants.

Design

EP infants (gestational age (GA) <28 weeks) were randomly allocated to TS or SS probiotic, assuring blinding. Reference (REF) group was EP infants in the placebo arm of our previous probiotic trial. PS was commenced with feeds and continued until 37 weeks’ corrected GA. Primary outcome was time to full feed (TFF: 150 mL/kg/day). Secondary outcomes included short-chain fatty acids and faecal microbiota collected at T1 (first week) and T2 (after 3 weeks of PS) using 16S ribosomal RNA gene sequencing.

Results

173 EP (SS: 86, TS: 87) neonates with similar GA and birth weight (BW) were randomised. Median TFF was comparable (11 (IQR 8–16) vs 10 (IQR 8–16) days, p=0.92). Faecal propionate (SS, p<0.001, and TS, p=0.0009) and butyrate levels (TS, p=0.029) were significantly raised in T2 versus T1 samples. Secondary clinical outcomes were comparable. At T2, alpha diversity was comparable (p>0.05) between groups, whereas beta-diversity analysis revealed significant differences between PS and REF groups (both p=0.001). Actinobacteria were higher (both p<0.01), and Proteobacteria, Firmicutes and Bacteroidetes were lower in PS versus REF. Gammaproteobacteria, Clostridia and Negativicutes were lower in both PS versus REF.

Conclusion

TFF in EP infants was similar between SS and TS probiotics. Both probiotics were effective in reducing dysbiosis (higher bifidobacteria and lower Gammaproteobacteria). Long-term significance of increased propionate and butyrate needs further studies.

Trial registration number

ACTRN 12615000940572.
Implementing care for healthy ageing
Authors: Cesari Matteo , Sumi Yuka , Han Zee A , Perracini Monica , Jang Hyobum , Briggs Andrew , Amuthavalli Thiyagarajan Jotheeswaran , Sadana Ritu , Banerjee Anshu
Published: February 2022

The WHO concept of Healthy Ageing (ie, the process of developing and maintaining the functional ability that enables well-being in older age) has initiated a global discussion about the need for shifting paradigms to reorient health and social services towards person-centred and coordinated models of care. In particular, the integration of health and social care services is critical to provide the basis for comprehensive information sharing and service delivery to support the evolution of the older person over time. The capability to monitor and respond to an older person’s changing health and social care needs will enable prompt and personalised health and social care plans to be implemented.

The implementation of an integrated care approach involves all the settings where persons age, but also requires a concerted action among micro (clinical), meso (service delivery) and macro (system) level. The community is of particular relevance given the primary objective of "ageing in place". However, from the perspective of the continuum of care and services acting synergistically, all health and social care settings (including long-term care facilities and hospitals) need to evolve and embrace an integrated way of operating to support functional ability in older people, while maximising resource and information sharing efficiencies.

In this paper, we explain that government actions to promote well-being in older age should be built on a seamless continuum of care starting from the assessment of the older person’s intrinsic capacity and functional ability with the final aim of providing care aligned with the individual’s needs and priorities.
Human rights in pandemics: criminal and punitive approaches to COVID-19
Authors: Sun Nina , Christie Emily , Cabal Luisa , Amon Joseph J
Published: February 2022

In the early years of the HIV epidemic, many countries passed laws criminalising HIV non-disclosure, exposure and/or transmission. These responses, intended to limit transmission and punish those viewed as ‘irresponsible’, have since been found to undermine effective HIV responses by driving people away from diagnosis and increasing stigma towards those living with HIV. With the emergence of COVID-19, human rights and public health advocates raised concerns that countries might again respond with criminal and punitive approaches. To assess the degree to which countries adopted such strategies, 51 English-language emergency orders from 39 countries, representing seven world regions, were selected from the COVID-19 Law Lab, a database of COVID-19 related laws from over 190 countries. Emergency orders were reviewed to assess the type of restrictions identified, enforcement mechanisms and compliance with principles outlined in the Siracusa Principles on the Limitation and Derogation Provisions in the International Covenant on Civil and Political Rights, including legality, legitimate aim, proportionality, non-discrimination, limited duration and subject to review. Approximately half of all orders examined included criminal sanctions related to violations of lockdowns. Few orders fully complied with the legal requirements for the limitation of, or derogation from, human rights obligations in public health emergencies. In future pandemics, policymakers should carefully assess the need for criminal and punitive responses and ensure that emergency orders comply with countries’ human rights obligations.
Use of a community advisory board to build equitable algorithms for participation in clinical trials: a protocol paper for HoPeNET
Authors: Farmer Nicole , Osei Baah Foster , Williams Faustine , Ortiz-Chapparo Erika , Mitchell Valerie M , Jackson Latifa , Collins Billy , Graham Lennox , Wallen Gwenyth R , Powell-Wiley Tiffany M , Johnson Allan
Published: February 2022

Introduction

Participation from racial and ethnic minorities in clinical trials has been burdened by issues surrounding mistrust and access to healthcare. There is emerging use of machine learning (ML) in clinical trial recruitment and evaluation. However, for individuals from groups who are recipients of societal biases, utilisation of ML can lead to the creation and use of biased algorithms. To minimise bias, the design of equitable ML tools that advance health equity could be guided by community engagement processes. The Howard University Partnership with the National Institutes of Health for Equitable Clinical Trial Participation for Racial/Ethnic Communities Underrepresented in Research (HoPeNET) seeks to create an ML-based infrastructure from community advisory board (CAB) experiences to enhance participation of African-Americans/Blacks in clinical trials.

Methods and analysis

This triphased cross-sectional study (24 months, n=56) will create a CAB of community members and research investigators. The three phases of the study include: (1) identification of perceived barriers/facilitators to clinical trial engagement through qualitative/quantitative methods and systems-based model building participation; (2) operation of CAB meetings and (3) development of a predictive ML tool and outcome evaluation. Identified predictors from the participant-derived systems-based map will be used for the ML tool development.

Ethics and dissemination

We anticipate minimum risk for participants. Institutional review board approval and informed consent has been obtained and patient confidentiality ensured.
Developing, implementing and governing artificial intelligence in medicine: a step-by-step approach to prevent an artificial intelligence winter
Authors: van de Sande Davy , Van Genderen Michel E , Smit Jim M. , Huiskens Joost , Visser Jacob J. , Veen Robert E. R. , van Unen Edwin , BA Oliver Hilgers , Gommers Diederik , Bommel Jasper van
Published: February 2022

Objective

Although the role of artificial intelligence (AI) in medicine is increasingly studied, most patients do not benefit because the majority of AI models remain in the testing and prototyping environment. The development and implementation trajectory of clinical AI models are complex and a structured overview is missing. We therefore propose a step-by-step overview to enhance clinicians’ understanding and to promote quality of medical AI research.

Methods

We summarised key elements (such as current guidelines, challenges, regulatory documents and good practices) that are needed to develop and safely implement AI in medicine.

Conclusion

This overview complements other frameworks in a way that it is accessible to stakeholders without prior AI knowledge and as such provides a step-by-step approach incorporating all the key elements and current guidelines that are essential for implementation, and can thereby help to move AI from bytes to bedside.
Nrf2 activation in the human brain after stroke due to supratentorial intracerebral haemorrhage: a case–control study
Authors: Christopher Edward , Loan James J M , Samarasekera Neshika , McDade Karina , Rose Jamie , Barrington Jack , Hughes Jeremy , Smith Colin , Al-Shahi Salman Rustam
Published: February 2022

Aims

Pharmacological activation of the antioxidative transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) improves outcomes in experimental models of intracerebral haemorrhage (ICH). However, the Nrf2 pathway has not been previously studied in humans after ICH. Our study aims to address this gap.

Methods

We selected cases with fatal ICH from a prospective community-based inception cohort study and age-matched and sex-matched controls who died suddenly of non-neurological disease. We used immunohistochemistry to quantify Nrf2 (% total area stained overall and % of nuclei stained) and CD68 expression in controls and perihaematomal, ipsilateral and contralateral brain tissue from cases. We measured downstream haem oxygenase-1 (HMOX1) and NAD(P)H dehydrogenase quinone 1 [NQO1] expression using RNA in situ hybridisation.

Results

26 ICH cases (median age: 82 (IQR 76–86); 13 (50%) male) and eight controls (median age: 79 (IQR 77–80); 3 (37.5%) male) were included. We found no significant differences in overall % of Nrf2 staining between ICH cases and controls. However, the mean % of nuclei staining for Nrf2 seemed higher in perihaematomal compared with contralateral regions, although this was only statistically significant >60 days after ICH (25% (95% CI 17% to 33%) vs 14% (95% CI 11% to 17%), p=0.029). The percentage of perihaematomal tissue staining for CD68 was higher >60 days after ICH (6.75%, 95% CI 2.78% to 10.73%) compared with contralateral tissue (1.45%, 95% CI 0.93% to 1.96%, p=0.027) and controls (1.08%, 95% CI 0.20% to 1.97%, p=0.0008). RNA in situ hybridisation suggested increased abundance of HMOX1 and NQO1 transcripts in perihaematomal versus distant ipsilateral brain tissue obtained <7 days from onset of ICH.

Conclusions

We found evidence of Nrf2 activation in human brain tissue after ICH. Pharmacological augmentation of Nrf2 activation after ICH might be a promising therapeutic approach.
Pattern and prevalence of eye disorders and diseases in school-aged children: findings from the Nationwide School Sight Sampling Survey in Armenia
Authors: Jrbashyan Nairuhi , Yeghiazaryan Nune , Sikder Abu , Nallasamy Sudha , Reid Mark W , Ohanesian Roger , Lee Thomas C , Espinoza Juan
Published: February 2022

Objective

This study aims to identify the prevalence of eye disorders and their causes among secondary schoolchildren aged 6–15 years old in Armenia, based on analysis of the Nationwide School Sight Sampling Survey.

Methods and Analysis

A two-stage proportionate stratified cluster sample was designed for the survey. 22 600 students were screened for visual acuity in schools; 5944 of them were selected for analysis as a nationally representative sample. Those with 20/40 or worse vision were referred to photoscreening and rapid ophthalmic assessment in schools and then were provided with vouchers for free comprehensive eye examination in eye clinics. Data were collected through data collection forms and analysed using SPSS V.23.

Results

While majority of the children (85%) had normal vision, 15% had a visual acuity ≤20/40. The prevalence of vision impairment (VI) in at least one eye was 9.7% and blindness in at least one eye was 0.05%. The prevalence of abnormal vision and VI was higher among girls and older children. VI was more prevalent in urban areas. The most common diagnoses were myopia (60%), astigmatism (33.7%), hyperopia (29.5%) and strabismus (3.8%).

Conclusion

Majority of the vision abnormalities and VI among schoolchildren are a result of refractive error and are treatable. Our results highlight the importance of regular eye examinations for schoolchildren to detect and prevent VI. Raising awareness among parents, school staff and children about eye health is vital.
Development of a patient decision aid for the initiation of urate-lowering therapy in gout patients
Authors: te Kampe Ritch , Boonen Annelies , Jansen Tim , Janssen Matthijs , de Vries Hein , van Durme Caroline
Published: February 2022

Aim

Shared decision-making improves patients’ experiences with care, satisfaction with management decisions and possibly health outcomes. This study describes the development of a decision aid (DA) that supports patients with gout and their physicians in a face-to-face clinical setting to (a) decide whether or not to (re)start urate-lowering therapy (ULT) and (b) agree on the preferred ULT.

Methods

Recommendations of the International Patient Decision Aid Standards group guided the development. A steering group of experts in gout and health services research specified the scope. Nominal group technique meetings were organised in which patients ranked the importance of preidentified potential characteristics/attributes of ULT and discussed further needs regarding the DA. A literature search was conducted to collect evidence on gout outcomes with and without ULT. Subsequently, the DA prototype was designed and adjusted using feedback from the steering group and results of cognitive debriefing interviews among five gout patients.

Results

The final DA consists of six pages. First, the DA clarifies the decision at stake and describes gout including its risk factors, the role of lifestyle and treatment of flares. Next, risk of future flares with and without ULT in relation to serum uric acid levels is described and visualised. Relevant attributes of ULT are presented in an option grid distinguishing first-line and second-line ULT. Finally, patients’ believes and preferences are explicitly addressed before making the shared decision.

Conclusion

This study provides initial support for usability of a DA for gout patients eligible for starting ULT.
The physical leaky tank car problem, revisited
Authors: Esposito S. , Olimpo M.
Published: February 2022

An exhaustive analysis of the leaky tank car problem is presented, pointing out its intriguing physical properties, which also well serve to students and teachers for illustrating standard Newtonian mechanics in a highly nonstandard fashion. Calculus is effectively required only to examine some details concerning the solution of the equation of motion and interesting limiting cases, while we unveil all the physical content of the problem, within a proper simple model and its generalization, ranging from the motion of the leaky tank car to that of the water flowing from the car with their peculiarities. Generalizations of the problem to more than one draining hole (even with different sizes), as well as to “two-dimensional” geometries, reveal further intriguing results, culminating into a no-rotation theorem and its corollaries.
A novel computational approach for a nonlinear fractional model of plasma physics
Authors: Talarposhti R. A. , Alipour Mohsen , Ghasemi S. E.
Published: February 2022

In the current study, a well-known fractional nonlinear differential equation called Zakharov–Kuznetsov equation which has many applications in engineering and physics is investigated. An effective computational techniques namely Daftardar–Jafari Method (DJM) and He’s fractional derivative are employed to model the problem for obtaining a high accuracy of the analytical solution. The governing equations are solved and comparison of the results with exact solutions is presented to evaluate the precision of the presented method. The outcomes reveal that the DJM is efficient and easy to utilize. Further, three-dimensional contour plots are depicted according to the suitable parameters values.
Stability control of a fractional-order Morris–Lecar neuronal model via fractional-order washout filter
Authors: Yue Kelong , Yang Renhuan , Yang Xiuzeng , Cai Qingwen , Shen Chao , Yang Liu
Published: February 2022

The bifurcation phenomenon generated in neurons is considered to be the cause of many neurological diseases, thus, lots of investigators have been dedicated to bifurcation control, but most of them only focus on the integer-order neuronal models and control methods. Recently, increasing number of research works have shown that the differential equations of fractional-order are more appropriate for description of the electrical properties of certain nerve cell membranes. In this paper, we employ a fractional-order washout filter to realize bifurcation control for fractional-order Morris–Lecar neuronal model. Computer simulation verifies the effectiveness and improved performance of the proposed method than the integer-order washout filter. In addition, the analysis of the fractional-order controller’s impacts on the model is also presented.
Automatically Extracting Bridge Frequencies Using SSA and K-Means Clustering from Vehicle-Scanned Accelerations
Authors: Yang Y. B. , He Yi , Xu Hao
Published: February 2022

This paper removes the subjective judgment by proposing a technique for automatically identifying the bridge frequencies using singularity spectrum analysis and [Formula: see text]-means clustering. First, the vehicle-bridge contact-point acceleration newly derived from is used to avoid the adverse effect brought by vehicle’s frequency. Next, the contact signal is processed by singular spectrum analysis to remove the noises. Then, the first several principal components are processed by the FFT to extract peak frequencies. Finally, the [Formula: see text]-means clustering algorithm is adopted to group the peak frequencies into clusters, with their centroids denoting the bridge frequencies. They are verified against those extrapolated from the 1st bridge frequency. Moreover, the current technique was assessed by studies on factors including pavement roughness, vehicle velocity, ongoing traffic, and vehicle stiffness, along with a field test on a bridge to demonstrate its capability. One feature of the current method is that the errors for higher frequencies predicted are not higher than lower frequencies.
Analysis of the Robustness of the Operational Performance Using a Combined Model of the Design of Experiment and Goal Programming Approaches for a Flexible Manufacturing Cell
Authors: Tansel İç Yusuf , Yurdakul Mustafa , Dengiz Berna , Şaşmaz Turgut
Published: February 2022

A combined model of a 2k design of experiment (DOE) and goal programming (GP) approaches is presented to determine optimum levels of input variables and analyze their robustness for a multiobjective performance of a flexible manufacturing cell (FMC) in this study. Two main performance metrics, namely, manufacturing lead time (MLT) and surface roughness (SR), are considered performance outputs for the FMC. Machine sequence, robot speed, tool type, and material type are selected as the four input variables on the input side of the proposed model. The study shows that even with a limited number of experiments, one can determine optimum input levels for the multiobjective performance of the FMC and determine their robustness.