bluuebunny/crossref_metadata_2025 huggingface dataset:
Heavy Metal Contamination in Oryza sativa L. at the Eastern Region of Malaysia and Its Risk Assessment
Authors: Zulkafflee Nur Syahirah , Mohd Redzuan Nurul Adillah , Nematbakhsh Sara , Selamat Jinap , Ismail Mohd Razi , Praveena Sarva Mangala , Yee Lee Soo , Abdull Razis Ahmad Faizal
Published: January 2022

Paddy plants tend to accumulate heavy metals from both natural and anthropogenic sources, and this poses adverse risks to human health. The objective of this study was to investigate heavy metal contamination in paddy plants in Kelantan, Malaysia, and its health risk assessment. The bioaccumulation of heavy metals was studied by means of enrichment (EF) and translocation factors (TF). The health risk assessment was performed based on USEPA guidelines. The EF for heavy metals in the studied areas was in the descending order of Cu > As > Cr > Cd > Pb. Meanwhile, Cr and Pb exhibited higher TF values from stem to grain compared with the others. The combined hazard index (HI) resulting from five heavy metals exceeded the acceptable limit (HI >1). The lifetime cancer risk, in both adult and children, was beyond the acceptable limit (10−4) and mainly resulted from exposure. The total cancer risk (CRt) due to simultaneous exposures to multiple carcinogenic elements also exceeded 10−4. In conclusion, intake of heavy metal through rice ingestion is likely to cause both non-carcinogenic and carcinogenic health risks. Further research is required to investigate the extent of heavy metal contamination in agricultural soils and, moreover, to establish human exposure as a result of rice consumption.
What Does a Systems Approach to Quality Improvement Look Like in Practice?
Authors: Williams Sharon J. , Best Stephanie
Published: January 2022

Universally improving healthcare systems is difficult to achieve in practice with organisations implementing a range of quality improvement (QI) approaches, in varying and changing contexts, and efforts ranging from project-based improvements to whole system change. This study aimed to identify how organisations overcome the challenges to improving the quality of the services they deliver. Drawing on the eight challenges from the ‘Quality and Safety in Europe by Research (QUASER) hospital guide, we assessed eight cases reported by the UK-based regulator Care Quality Commission as improving their performance. A thematic analysis of these secondary data established that all eight challenges had been addressed or considered in varying degrees. Education and physical and technological challenges seemed less prominent than developments made to address other challenges such as developing leadership, structure, and culture to support improving quality. This paper relies on the analysis of secondary case data and one framework to assess improvement efforts. Further research is required to consider other models and frameworks and to collate longitudinal data to capture the dynamics and increasing the maturity of improving healthcare systems in practice.
Impact of Thermal Dissipation on the Lighting Performance and Useful Life of LED Luminaires Applied to Urban Lighting: A Case Study
Authors: Unión-Sánchez Juan de Dios , Hermoso-Orzáez Manuel Jesús , Hervás-Pulido Manuel Jesús , Ogáyar-Fernández Blas
Published: January 2022

Currently, LED technology is an established form of lighting in our cities and homes. Its lighting performance, durability, energy efficiency and light, together with the economic savings that its use implies, are displacing other classic forms of lighting. However, some problems associated with the durability of the equipment related to the problems of thermal dissipation and high temperature have begun to be detected, which end up affecting their luminous intensity and the useful life. There are many studies that show a direct relationship between the low quality of LED lighting and the aging of the equipment or its overheating, observing the depreciation of the intensity of the light and the visual chromaticity performance that can affect the health of users by altering circadian rhythms. On the other hand, the shortened useful life of the luminaires due to thermal stress has a direct impact on the LCA (Life Cycle Analysis) and its environmental impact, which indirectly affects human health. The purpose of this article is to compare the results previously obtained, at different contour temperatures, by theoretical thermal simulation of the 3D model of LED street lighting luminaires through the ANSYS Fluent simulation software. Contrasting these results with the practical results obtained with a thermal imaging camera, the study shows how the phenomenon of thermal dissipation plays a fundamental role in the lighting performance of LED technology. The parameter studied in this work is junction temperature (Tj), and how it can be used to predict the luminous properties in the design phase of luminaires in order to increase their useful life.
Developmental Dental Defects in Permanent Teeth Resulting from Trauma in Primary Dentition: A Systematic Review
Authors: Caeiro-Villasenín Lucía , Serna-Muñoz Clara , Pérez-Silva Amparo , Vicente-Hernández Ascensión , Poza-Pascual Andrea , Ortiz-Ruiz Antonio José
Published: January 2022

The objective was to determine whether trauma in primary dentition causes alterations in the development of permanent dentition. Searches were made in May 2020 using PubMed, MEDLINE, MEDES, Scopus, Lilacs, and Embase. Papers in English, German, and Spanish, without restrictions in the year of publication, were included. The quality of the studies was analyzed using the NOS Scale. The search retrieved 537 references, and seven studies were included for a qualitative analysis. The results showed that trauma to a deciduous tooth can damage the bud of the permanent tooth. Enamel discoloration and/or hypoplasia were the most common sequelae in the permanent teeth after trauma to the primary predecessor. The type and severity of sequelae in the permanent tooth are associated with the development phase of the bud. Children with trauma of their primary teeth should receive checkups until the eruption of the permanent teeth for the early diagnosis and treatment of possible sequelae. Intrusion of the primary tooth was the trauma that caused the most damage and enamel alterations the most frequent sequelae.
Development and Application of a QGIS-Based Model to Estimate Monthly Streamflow
Authors: Lee Hanyong , Chae Min Suh , Park Jong-Yoon , Lim Kyoung Jae , Park Youn Shik
Published: January 2022

Changes in rainfall pattern and land use have caused considerable impacts on the hydrological behavior of watersheds; a Long-Term Hydrologic Impact Analysis (L-THIA) model has been used to simulate such variations. The L-THIA model defines curve number according to the land use and hydrological soil group before calculating the direct runoff based on the amount of rainfall, making it a convenient method of analysis. Recently, a method was proposed to estimate baseflow using this model, which may be used to estimate the overall streamflow. Given that this model considers the spatial distribution of land use and hydrological soil groups and must use rainfall data at multiple positions, it requires the usage of a geographical information system (GIS). Therefore, a model that estimates streamflow using land use maps, hydrologic soil group maps, and rain gauge station maps in QGIS, a popular GIS software, was developed. This model was tested in 15 watersheds.
GIS-Based Approach for the Analysis of Geographical Education Paths
Authors: Jażdżewska Iwona Anna , Lechowski Łukasz , Babuca Dominika
Published: January 2022

This paper presents a new geospatial approach, and a proposal to study the geographic educational path of individuals or social groups identified by researchers using a Geographic Information System (GIS) and spatial statistics. A scheme of research proceedings has been proposed, including obtaining data from various sources (including surveys and other sources, e.g., from the university and OpenStreetMap), their proper preparation and categorisation into one geodatabase on the GIS system, followed by visualisation and the calculation of statistics. The whole research procedure was carried out in GIS. The results can be useful for detecting patterns of educational paths in different countries and social groups, and comparing them. Indirectly, they can be used to study mobility, and to indicate the spatial range of studied schools. The study was carried out among a group of students of geoinformation at the University of Lodz. Visualization and analysis of their geographical educational path showed that most of them attended schools close to where they lived, indicating low mobility during their education. The results obtained may be relevant to the “spatial turn” in education research.
Improvement of Oracle Bone Inscription Recognition Accuracy: A Deep Learning Perspective
Authors: Fu Xuanming , Yang Zhengfeng , Zeng Zhenbing , Zhang Yidan , Zhou Qianting
Published: January 2022

Deep learning techniques have been successfully applied in handwriting recognition. Oracle bone inscriptions (OBI) are the earliest hieroglyphs in China and valuable resources for studying the etymology of Chinese characters. OBI are of important historical and cultural value in China; thus, textual research surrounding the characters of OBI is a huge challenge for archaeologists. In this work, we built a dataset named OBI-100, which contains 100 classes of oracle bone inscriptions collected from two OBI dictionaries. The dataset includes more than 128,000 character samples related to the natural environment, humans, animals, plants, etc. In addition, we propose improved models based on three typical deep convolutional network structures to recognize the OBI-100 dataset. By modifying the parameters, adjusting the network structures, and adopting optimization strategies, we demonstrate experimentally that these models perform fairly well in OBI recognition. For the 100-category OBI classification task, the optimal model achieves an accuracy of 99.5%, which shows competitive performance compared with other state-of-the-art approaches. We hope that this work can provide a valuable tool for character recognition of OBI.
Interoperability and Integration: An Updated Approach to Linked Data Publication at the Dutch Land Registry
Authors: Rowland Alexandra , Folmer Erwin , Beek Wouter , Wenneker Rob
Published: January 2022

Kadaster, the Dutch National Land Registry and Mapping Agency, has been actively publishing their base registries as linked (open) spatial data for several years. To date, a number of these base registers as well as a number of external datasets have been successfully published as linked data and are publicly available. Increasing demand for linked data products and the availability of new linked data technologies have highlighted the need for a new, innovative approach to linked data publication within the organisation in the interest of reducing the time and costs associated with said publication. The new approach to linked data publication is novel in both its approach to dataset modelling, transformation, and publication architecture. In modelling whole datasets, a clear distinction is made between the Information Model and the Knowledge Model to capture both the organisation-specific requirements and to support external, community standards in the publication process. The publication architecture consists of several steps where instance data are loaded from their source as GML and transformed using an Enhancer and published in the triple store. Both the modelling and publication architecture form part of Kadaster’s larger vision for the development of the Kadaster Knowledge Graph through the integration of the various linked datasets.
Study Design for an Evaluation of Newborn Screening for SCID in the UK
Authors: Elliman David
Published: January 2022

Severe combined immunodeficiency is a rare inherited disorder, which, if untreated, invariably proves fatal in late infancy or early childhood. With treatment, the prognosis is much improved. Early treatment of the siblings of cases, before they become symptomatic, has shown considerable improvements in outcomes. Based on this and the development of a test that can be used on the whole population of neonates (measurement of T-cell receptor excision circles—TRECs), many countries have added it to their routine newborn bloodspot screening programmes. The UK National Screening Committee (UKNSC) has considered whether SCID should be added to the UK screening programme and concluded that it was likely to be cost effective, but that there were a number of uncertainties that should be resolved before a national roll-out could be recommended. These include some aspects of the test, such as: cost; the use of different assays and cut-off levels to reduce false positive rates, while maintaining sensitivity; the overall benefits of screening for disease outcome in patients with SCID and other identified disorders; the need for a separate pathway for premature babies; the acceptability of the screening programme to parents of babies who have normal and abnormal (both true and false positive) screening results. To achieve this, screening of two thirds of babies born in England over a two-year period has been planned, beginning in September 2021. The outcomes and costs of care of babies identified by the screening will be compared with those of babies identified with SCID in the rest of the UK. The effect of the screening programme on parents will form part of a separate research project.
Extraction and Analysis of Social Networks Data to Detect Traffic Accidents
Authors: Suat-Rojas Nestor , Gutierrez-Osorio Camilo , Pedraza Cesar
Published: January 2022

Traffic accident detection is an important strategy governments can use to implement policies intended to reduce accidents. They usually use techniques such as image processing, RFID devices, among others. Social network mining has emerged as a low-cost alternative. However, social networks come with several challenges such as informal language and misspellings. This paper proposes a method to extract traffic accident data from Twitter in Spanish. The method consists of four phases. The first phase establishes the data collection mechanisms. The second consists of vectorially representing the messages and classifying them as accidents or non-accidents. The third phase uses named entity recognition techniques to detect the location. In the fourth phase, locations pass through a geocoder that returns their geographic coordinates. This method was applied to Bogota city and the data on Twitter were compared with the official traffic information source; comparisons showed some influence of Twitter on the commercial and industrial area of the city. The results reveal how effective the information on accidents reported on Twitter can be. It should therefore be considered as a source of information that may complement existing detection methods.
Inhibitory Control in Children with Tourette Syndrome Is Impaired in Everyday Life but Intact during a Stop Signal Task
Authors: Ritter Melanie , Vangkilde Signe Allerup , Maigaard Katrine , Pagsberg Anne Katrine , Plessen Kerstin Jessica , Hagstrøm Julie
Published: January 2022

Tourette Syndrome (TS) has previously been associated with deficits in inhibitory control (IC). However, studies on IC in individuals with TS have produced conflicting results. In the present study, we investigated IC, comparing the Stop Signal Reaction Time (SSRT) measure with parent and teacher ratings of daily life IC in 169 children aged 8–12 (60 with TS, 60 typically developing controls, 27 with attention-deficit/hyperactivity disorder (ADHD), and 22 with TS + ADHD). We further investigated associations of IC with TS and ADHD symptom severity. Children with TS showed intact SSRT performance, but impairments in daily life IC, as reported by parents and teachers. For the latter, we observed a staircase distribution of groups, with the healthy controls presenting with the best IC, followed by TS, TS + ADHD, and finally ADHD. Dimensional analyses indicated a strong association between ADHD severity and both measures of IC. Our results indicate that children with TS are not impaired in a laboratory-based measure of IC, although some difficulties were evident from measures of everyday behaviour, which may in part be due to parents and teachers interpreting tics as disinhibited behaviour. Comorbid ADHD or the severity of subthreshold ADHD symptomatology appeared to account for IC deficits.
Post-Ureteroscopy Infections Are Linked to Pre-Operative Stent Dwell Time over Two Months: Outcomes of Three European Endourology Centres
Authors: Geraghty Robert M. , Pietropaolo Amelia , Villa Luca , Fitzpatrick John , Shaw Matthew , Veeratterapillay Rajan , Rogers Alistair , Ventimiglia Eugenio , Somani Bhaskar K.
Published: January 2022

Background: The aim of this study is to investigate outcomes of pre-operative stent dwell time on infectious complications following ureteroscopy and stone treatment to identify a time cut-off. Material and Methods: Three tertiary referral centres in Europe retrospectively collected outcomes of ureteroscopy and laser fragmentation (URSL) for all patients with pre-operative indwelling ureteric stents over a period of up to 5 years. Data was collected on patient details, stone demographics, stent dwell time, complications and stone free rate (SFR). Matching for age, sex, operative time, stone size and post-operative stent insertion. To examine for a threshold effect, monthly cut-offs were used to compare post-ureteroscopic febrile UTIs. Binomial logistic regression was used (SPSS v.24) with a significance level set at 0.0036. The risk ratio (RR) with a 95% confidence interval (CI) and the number needed to harm (NNH) are reported. Results: There were 467 patients with a pre-operative stent for analysis. These patients (n = 315) were matched to non-stented controls after excluding 152 patients to achieve adequate matching. There was a significant difference in rates of post-ureteroscopic febrile UTI between stented vs non-stented patients (RR = 2.67, 95% CI: 1.10–6.48, p = 0.03). On adjustment, a dwell time of more than two months was associated with an increased risk of post-ureteroscopic febrile UTI (RR = 3.94, 95% CI: 1.30–12.01, p = 0.02), this increased risk rose with longer dwell time. At stent time longer than four months was associated with a significantly increased risk of post-ureteroscopic febrile UTI (5% vs. 15%, RR = 3.09, 95% CI: 1.56–6.10, p = 0.001), with the number needed to harm at 10. Conclusions: Overall infectious complication rates from URSL are low. The risk of post-operative UTI after four months of dwell time is nearly tripled compared to less than four months.
Discordance between LDL-C and Apolipoprotein B Levels and Its Association with Renal Dysfunction: Insights from a Population-Based Study
Authors: Mazidi Mohsen , Webb Richard J. , Lip Gregory Y. H. , Kengne Andre P. , Banach Maciej , Davies Ian G.
Published: January 2022

Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) are established markers of atherosclerotic cardiovascular disease (ASCVD), but when concentrations are discordant ApoB is the superior predictor. Chronic kidney disease (CKD) is associated with ASCVD, yet the independent role of atherogenic lipoproteins is contentious. Four groups were created based upon high and low levels of ApoB and LDL-C. Continuous and categorical variables were compared across groups, as were adjusted markers of CKD. Logistic regression analysis assessed association(s) with CKD based on the groups. Subjects were categorised by LDL-C and ApoB, using cut-off values of >160 mg/dL and >130 mg/dL, respectively. Those with low LDL-C and high ApoB, compared to those with high LDL-C and high ApoB, had significantly higher body mass index (30.7 vs. 30.1 kg/m2) and waist circumference (106.1 vs. 102.7 cm) and the highest fasting blood glucose (117.5 vs. 112.7 mg/dL), insulin (16.6 vs. 13.1 μU/mL) and homeostatic model assessment of insulin resistance (5.3 vs. 3.7) profiles (all p < 0.001). This group, compared to those with high LDL-C and high ApoB, also had the highest levels of urine albumin (2.3 vs. 2.2 mg/L), log albumin-creatinine ratio (2.2 vs. 2.1 mg/g) and serum uric acid (6.1 vs. 5.6 mg/dL) and the lowest estimated glomerular filtration rate (81.3 vs. 88.4 mL/min/1.73 m2) (all p < 0.001). In expanded logistic regression models, using the low LDL-C and low ApoB group as a reference, those with low LDL-C and high ApoB had the strongest association with CKD, odds ratio (95% CI) 1.12 (1.08–1.16). Discordantly high levels of ApoB are independently associated with increased likelihood of CKD. ApoB remains associated with metabolic dysfunction, regardless of LDL-C.
Scleral Buckling: A Review of Clinical Aspects and Current Concepts
Authors: Fallico Matteo , Alosi Pietro , Reibaldi Michele , Longo Antonio , Bonfiglio Vincenza , Avitabile Teresio , Russo Andrea
Published: January 2022

Scleral buckling represents a valuable treatment option for rhegmatogenous retinal detachment repair. The surgery is based on two main principles: the closure of retinal breaks and the creation of a long-lasting chorioretinal adhesion. Buckles are placed onto the sclera with the purpose of sealing retinal breaks. Cryopexy is usually performed to ensure a long-lasting chorioretinal adhesion. Clinical outcomes of scleral buckling have been shown to be more favorable in phakic eyes with uncomplicated or medium complexity retinal detachment, yielding better anatomical and functional results compared with vitrectomy. Several complications have been described following scleral buckling surgery, some of which are sight-threatening. Expertise in indirect ophthalmoscopy is required to perform this type of surgery. A great experience is necessary to prevent complications and to deal with them. The use of scleral buckling surgery has declined over the years due to increasing interest in vitrectomy. Lack of confidence in indirect ophthalmoscopy and difficulties in teaching this surgery have contributed to limiting its diffusion among young ophthalmologists. The aim of this review is to provide a comprehensive guide on technical and clinical aspects of scleral buckling, focusing also on complications and their management.
A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics
Authors: Peter Madeleine St. , Warnecke Athanasia , Staecker Hinrich
Published: January 2022

In the clinical setting, the pathophysiology of sensorineural hearing loss is poorly defined and there are currently no diagnostic tests available to differentiate between subtypes. This often leaves patients with generalized treatment options such as steroids, hearing aids, or cochlear implantation. The gold standard for localizing disease is direct biopsy or imaging of the affected tissue; however, the inaccessibility and fragility of the cochlea make these techniques difficult. Thus, the establishment of an indirect biopsy, a sampling of inner fluids, is needed to advance inner ear diagnostics and allow for the development of novel therapeutics for inner ear disease. A promising source is perilymph, an inner ear liquid that bathes multiple structures critical to sound transduction. Intraoperative perilymph sampling via the round window membrane of the cochlea has been successfully used to profile the proteome, metabolome, and transcriptome of the inner ear and is a potential source of biomarker discovery. Despite its potential to provide insight into inner ear pathologies, human perilymph sampling continues to be controversial and is currently performed only in conjunction with a planned procedure where the inner ear is opened. Here, we review the safety of procedures in which the inner ear is opened, highlight studies where perilymph analysis has advanced our knowledge of inner ear diseases, and finally propose that perilymph sampling could be done as a stand-alone procedure, thereby advancing our ability to accurately classify sensorineural hearing loss.
Imaging Challenges in Patients with Severe Aortic Stenosis and Heart Failure: Did We Find a Way Out of the Labyrinth?
Authors: Gonska Birgid , Buckert Dominik , Mörike Johannes , Scharnbeck Dominik , Kersten Johannes , Cuspidi Cesare , Rottbauer Wolfang , Tadic Marijana
Published: January 2022

Aortic stenosis (AS) is the most frequent degenerative valvular disease in developed countries. Its incidence has been constantly rising due to population aging. The diagnosis of AS was considered straightforward for a very long time. High gradients and reduced aortic valve area were considered as “sine qua non” in diagnosis of AS until a growing body of evidence showed that patients with low gradients could also have severe AS with the same or even worse outcome. This completely changed the paradigm of AS diagnosis and involved large numbers of parameters that had never been used in the evaluation of AS severity. Low gradient AS patients may present with heart failure (HF) with preserved or reduced left ventricular ejection fraction (LVEF), associated with changes in cardiac output and flow across the aortic valve. These patients with low-flow low-gradient or paradoxical low-flow low-gradient AS are particularly challenging to diagnose, and cardiac output and flow across the aortic valve have become the most relevant parameters in evaluation of AS, besides gradients and aortic valve area. The introduction of other imaging modalities in the diagnosis of AS significantly improved our knowledge about cardiac mechanics, tissue characterization of myocardium, calcium and inflammation burden of the aortic valve, and their impact on severity, progression and prognosis of AS, not only in symptomatic but also in asymptomatic patients. However, a variety of novel parameters also brought uncertainty regarding the clinical relevance of these indices, as well as the necessity for their validation in everyday practice. The aim of this review is to summarize the prevalence of HF in patients with severe AS and elaborate on the diagnostic challenges and advantages of comprehensive multimodality cardiac imaging to identify the patients that may benefit from surgical or transcatheter aortic valve replacement, as well as parameters that may help during follow-up.
Evidence-Based Mechanical Ventilatory Strategies in ARDS
Authors: Liaqat Adnan , Mason Matthew , Foster Brian J. , Kulkarni Sagar , Barlas Aisha , Farooq Awais M. , Patak Pooja , Liaqat Hamza , Basso Rafaela G. , Zaman Mohammed S. , Pau Dhaval
Published: January 2022

Acute respiratory distress syndrome (ARDS) remains one of the leading causes of morbidity and mortality in critically ill patients despite advancements in the field. Mechanical ventilatory strategies are a vital component of ARDS management to prevent secondary lung injury and improve patient outcomes. Multiple strategies including utilization of low tidal volumes, targeting low plateau pressures to minimize barotrauma, using low FiO2 (fraction of inspired oxygen) to prevent injury related to oxygen free radicals, optimization of positive end expiratory pressure (PEEP) to maintain or improve lung recruitment, and utilization of prone ventilation have been shown to decrease morbidity and mortality. The role of other mechanical ventilatory strategies like non-invasive ventilation, recruitment maneuvers, esophageal pressure monitoring, determination of optimal PEEP, and appropriate patient selection for extracorporeal support is not clear. In this article, we review evidence-based mechanical ventilatory strategies and ventilatory adjuncts for ARDS.
Sirolimus-Based Immunosuppression Is Associated with Decreased Incidence of Post-Transplant Lymphoproliferative Disorder after Heart Transplantation: A Double-Center Study
Authors: Asleh Rabea , Vucicevic Darko , Petterson Tanya M. , Kremers Walter K. , Pereira Naveen L. , Daly Richard C. , Edwards Brooks S. , Steidley D. Eric , Scott Robert L. , Kushwaha Sudhir S.
Published: January 2022

Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein–Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8–26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04–0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03–0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk.
Managing Neovascular Age-Related Macular Degeneration in Clinical Practice: Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Veritti Daniele , Sarao Valentina , Soppelsa Valentina , Danese Carla , Chhablani Jay , Lanzetta Paolo
Published: January 2022

The use of anti-vascular endothelial growth factor (VEGF) agents has profoundly changed the prognosis of neovascular age-related macular degeneration (nAMD). As clinical experiences have accumulated, it has become mandatory to summarize data to give information that can be useful in everyday practice. We conducted a systematic review to identify randomized controlled trials (RCTs) and observational studies that reported 12-month changes in best-corrected visual acuity (BCVA) in patients with nAMD on anti-VEGF monotherapy. Data were analyzed in a random-effects meta-analysis with BCVA change as the primary outcome. Meta-regression was conducted to evaluate the impact of multiple covariates. Four hundred and twelve heterogeneous study populations (109,666 eyes) were included. Anti-VEGFs induced an overall improvement of +5.37 ETDRS letters at 12 months. Meta-regression showed that mean BCVA change was statistically greater for RCTs (p = 0.0032) in comparison with observational studies. Populations following a proactive regimen had better outcomes than those following a reactive treatment regimen. Mean BCVA change was greater in younger populations, with lower baseline BCVA and treated with a higher number of injections (p < 0.001). Our results confirm that anti-VEGFs may produce a significant functional improvement at 12 months in patients with nAMD.
Bone Mineral Density Compared to Trabecular Bone Score in Primary Hyperparathyroidism
Authors: Jones Alicia R. , Simons Koen , Harvey Susan , Grill Vivian
Published: January 2022

Individuals with primary hyperparathyroidism (PHPT) have reduced bone mineral density (BMD) according to dual X-ray absorptiometry at cortical sites, with relative sparing of trabecular BMD. However, fracture risk is increased at all sites. Trabecular bone score (TBS) may more accurately describe their bone quality and fracture risk. This study compared how BMD and TBS describe bone quality in PHPT. We conducted a retrospective cross-sectional study with a longitudinal component, of adults with PHPT, admitted to a tertiary hospital in Australia over ten years. The primary outcome was the TBS at the lumbar spine, compared to BMD, to describe bone quality and predict fractures. Secondary outcomes compared changes in TBS after parathyroidectomy. Of 68 included individuals, the mean age was 65.3 years, and 79% were female. Mean ± SD T-scores were −1.51 ± 1.63 at lumbar spine and mean TBS was 1.19 ± 0.12. Only 20.6% of individuals had lumbar spine BMD indicative of osteoporosis, while 57.4% of TBS were ≤1.20, indicating degraded architecture. There was a trend towards improved fracture prediction using TBS compared to BMD which did not reach statistical significance. Comparison of 15 individuals following parathyroidectomy showed no improvement in TBS.
Evidence-Based Surgical Treatment Algorithm for Unstable Syndesmotic Injuries
Authors: Regauer Markus , Mackay Gordon , Nelson Owen , Böcker Wolfgang , Ehrnthaller Christian
Published: January 2022

Background: Surgical treatment of unstable syndesmotic injuries is not trivial, and there are no generally accepted treatment guidelines. The most common controversies regarding surgical treatment are related to screw fixation versus dynamic fixation, the use of reduction clamps, open versus closed reduction, and the role of the posterior malleolus and of the anterior inferior tibiofibular ligament (AITFL). Our aim was to draw important conclusions from the pertinent literature concerning surgical treatment of unstable syndesmotic injuries, to transform these conclusions into surgical principles supported by the literature, and finally to fuse these principles into an evidence-based surgical treatment algorithm. Methods: PubMed, Embase, Google Scholar, The Cochrane Database of Systematic Reviews, and the reference lists of systematic reviews of relevant studies dealing with the surgical treatment of unstable syndesmotic injuries were searched independently by two reviewers using specific terms and limits. Surgical principles supported by the literature were fused into an evidence-based surgical treatment algorithm. Results: A total of 171 articles were included for further considerations. Among them, 47 articles concerned syndesmotic screw fixation and 41 flexible dynamic fixations of the syndesmosis. Twenty-five studies compared screw fixation with dynamic fixations, and seven out of these comparisons were randomized controlled trials. Nineteen articles addressed the posterior malleolus, 14 the role of the AITFL, and eight the use of reduction clamps. Anatomic reduction is crucial to prevent posttraumatic osteoarthritis. Therefore, flexible dynamic stabilization techniques should be preferred whenever possible. An unstable AITFL should be repaired and augmented, as it represents an important stabilizer of external rotation of the distal fibula. Conclusions: The current literature provides sufficient arguments for the development of an evidence-based surgical treatment algorithm for unstable syndesmotic injuries.
Surface Functionalization of Poly(l-lactide-co-glycolide) Membranes with RGD-Grafted Poly(2-oxazoline) for Periodontal Tissue Engineering
Authors: Tryba Anna M. , Krok-Borkowicz Małgorzata , Kula Michał , Piergies Natalia , Marzec Mateusz , Wegener Erik , Frączyk Justyna , Jordan Rainer , Kolesińska Beata , Scharnweber Dieter , Paluszkiewicz Czesława , Pamuła Elżbieta
Published: January 2022

Bone tissue defects resulting from periodontal disease are often treated using guided tissue regeneration (GTR). The barrier membranes utilized here should prevent soft tissue infiltration into the bony defect and simultaneously support bone regeneration. In this study, we designed a degradable poly(l-lactide-co-glycolide) (PLGA) membrane that was surface-modified with cell adhesive arginine-glycine-aspartic acid (RGD) motifs. For a novel method of membrane manufacture, the RGD motifs were coupled with the non-ionic amphiphilic polymer poly(2-oxazoline) (POx). The RGD-containing membranes were then prepared by solvent casting of PLGA, POx coupled with RGD (POx_RGD), and poly(ethylene glycol) (PEG) solution in methylene chloride (DCM), followed by DCM evaporation and PEG leaching. Successful coupling of RGD to POx was confirmed spectroscopically by Raman, Fourier transform infrared in attenuated reflection mode (FTIR-ATR), and X-ray photoelectron (XPS) spectroscopy, while successful immobilization of POx_RGD on the membrane surface was confirmed by XPS and FTIR-ATR. The resulting membranes had an asymmetric microstructure, as shown by scanning electron microscopy (SEM), where the glass-cured surface was more porous and had a higher surface area then the air-cured surface. The higher porosity should support bone tissue regeneration, while the air-cured side is more suited to preventing soft tissue infiltration. The behavior of osteoblast-like cells on PLGA membranes modified with POx_RGD was compared to cell behavior on PLGA foil, non-modified PLGA membranes, or PLGA membranes modified only with POx. For this, MG-63 cells were cultured for 4, 24, and 96 h on the membranes and analyzed by metabolic activity tests, live/dead staining, and fluorescent staining of actin fibers. The results showed bone cell adhesion, proliferation, and viability to be the highest on membranes modified with POx_RGD, making them possible candidates for GTR applications in periodontology and in bone tissue engineering.
CFD Research on the Hydrodynamic Performance of Submarine Sailing near the Free Surface with Long-Crested Waves
Authors: Dong Kai , Wang Xianzhou , Zhang Donglei , Liu Liwei , Feng Dakui
Published: January 2022

The simulations of submarine sailing near the free surface with long-crested waves have been conducted in this study using an in-house viscous URANS solver with an overset grid approach. First, the verification and validation procedures were performed to evaluate the reliability, with the results showing that the generation of irregular waves is adequately accurate and the results of total resistance are in good agreement with EFD. Next, three different submerged depths ranging from 1.1D to 3.3D were selected and the corresponding conditions of submarine sailing near calm water were simulated, the results of which were then compared with each other to investigate the influence of irregular waves and submerged depths. The simulations of the model near calm water at different submerged depths demonstrated that the free surface will cause increasing resistance, lift, and bow-up moments of the model, and this influence decreases dramatically with greater submerged depths. The results of the irregular wave simulations showed that irregular waves cause considerable fluctuations of hydrodynamic force and moments, and that this influence remains even at a deeper submerged depth, which can complicate the control strategies of the submarine. The response spectrum of hydrodynamic forces and moments showed slight amplitudes in the high-frequency region, and the model showed less sensitivity to high-frequency excitations.
The Risk Factors of Severe Hypoglycemia in Older Patients with Dementia and Type 2 Diabetes Mellitus
Authors: Chen Nai-Ching , Chen Chien-Liang , Shen Feng-Chih
Published: January 2022

Background: The adequate glycemic control and risk factors for hypoglycemia in older patients with dementia and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to analyze the status of glycemic control and determine the risk of hypoglycemia among these groups. Methods: A hospital admission record due to hypoglycemia through an emergency room with glucose supplementation in the Chang Gung Memorial Hospital was identified as a hypoglycemic event. Patients with dementia and T2DM without hypoglycemic events throughout the study period were defined as the control group. We gathered patients aged ≥65 years with a diagnosis of Alzheimer’s dementia (AD) and T2DM between 2001 and 2018 in the Chang Gung Research Database (CGRD). We extracted data included medication use, diagnoses, and biochemistry data from hospital records. Results: A total of 3877 older patients with dementia and T2DM with regular visits to the outpatient department were enrolled in this study. During the two-year follow-up period, 494 participants (12.7%) experienced hypoglycemia. Multivariable logistic multivariable regression models for hypoglycemic events showed that metformin had a protective effect (odds ratio (OR) = 0.75, p = 0.023), insulin had the highest risk (OR = 4.64, p < 0.001). Hemoglobin A1c (HbA1c) levels were not correlated with hypoglycemic events (OR = 0.95, p = 0.140). Patients with hypoglycemic episodes had a significantly higher proportion of ≥2 Charlson Comorbidity Index scores than those without hypoglycemic episodes (83.2% versus 56.4%, p < 0.001). Conclusions: Drug regimen affects hypoglycemic episodes but not HbA1c in older patients with dementia and T2DM. In addition, patients with more comorbidities experience an increased risk of hypoglycemia.
Evidence-Based Decision Support for a Structured Care Program on Polypharmacy in Multimorbidity: A Guideline Upgrade Based on a Realist Synthesis
Authors: Dinh Truc Sophia , Brueckle Maria-Sophie , González-González Ana Isabel , Fessler Joachim , Marschall Ursula , Schubert-Zsilavesz Manfred , Gerlach Ferdinand M. , Harder Sebastian , van den Akker Marjan , Schubert Ingrid , Muth Christiane ,   the EVITA Study Group
Published: January 2022

Evidence-based clinical guidelines generally consider single conditions, and rarely multimorbidity. We developed an evidence-based guideline for a structured care program to manage polypharmacy in multimorbidity by using a realist synthesis to update the German polypharmacy guideline including the following five methods: formal prioritization in focus groups; systematic guideline review of evidence-based multimorbidity/polypharmacy guidelines; evidence search/synthesis and recommendation development; multidisciplinary consent of recommendations; feasibility test of updated guideline. We identified the need for a better description of the target group, decision support, prioritization of medication, consideration of patient preferences and anticholinergic properties, and of healthcare interfaces. We conducted a systematic guideline review of eight guidelines and extracted and synthesized recommendations using the Ariadne principles. We also included 48 systematic reviews. We formulated and agreed upon 34 recommendations for the revised guideline. During the feasibility test, guideline use enabled 57% of GPs to identify problems, leading to medication changes in 49% and self-assessed improvement in 56% of patients. Although 58% of GPs felt that it was too long, 92% recommended it. Polypharmacy should be systematically reviewed at least annually. Patients, family members, and healthcare professionals should monitor and adjust it using prospective process validation, taking into account patient preferences and agreed treatment goals.
The Role of Cumulative LDL Cholesterol in Cardiovascular Disease Development in Patients with Familial Hypercholesterolemia
Authors: Korneva Victoria , Kuznetsova Tatyana , Julius Ulrich
Published: January 2022

In patients with familial hypercholesterolemia (FH) the exposure of very high LDL-C concentration and cumulative LDL-C level (cum LDL-C) can play a significant role in the prognosis. Objective: to analyze the contribution of “cum LDL-C for all life” and the index “cum LDL-C/age” to the development of coronary heart disease (CHD), myocardial infarction (MI), and a combined end point: MI, stroke, unstable angina in FH patients. Methods: 188 patients (mean age 49.2 years, males 45.7%) with FH were examined (Dutch Lipid Clinic Criteria). We had evaluated cumulative LDL-C and index “cum DL-C/age” along with other classical risk factors. Cum LDL-C was calculated as LDL-Cmax × (age at initiating of hypolipidemic therapy) + LDL-C at inclusion age at initiation/correction therapy). Cumulative LDL-C and “cum LDL-C/age” were calculated as the ratio cum LDL-C to age. The follow-up period was 5.4 (from 3 to 10) years. Results: The index “cum LDL-C/age” was higher in patients with CHD 58.7 ± 10.4 mmol/L/years vs. 40.1 ± 11.7 mmol/L/years in patients without CHD (p < 0.001). According to our data based on the results of the logistic regression analysis in patients with FH, cumulative LDL-C and the cumulative index “cum LDL–C/age” played a strong predictive role in the development of CHD in FH patients; it was greater than the role of TC and LDL-C concentrations. We present ROC curves for CHD, MI and combined end point in FH patients, and a prognostic scale for CHD development, which is based on classical cardiovascular risk factors. Conclusion: cumulative LDL-C level plays an important role in the development of CHD in FH patients.
Identifying the Steps Required to Effectively Implement Next-Generation Sequencing in Oncology at a National Level in Europe
Authors: Horgan Denis , Curigliano Giuseppe , Rieß Olaf , Hofman Paul , Büttner Reinhard , Conte Pierfranco , Cufer Tanja , Gallagher William M. , Georges Nadia , Kerr Keith , Penault-Llorca Frédérique , Mastris Ken , Pinto Carla , Van Meerbeeck Jan , Munzone Elisabetta , Thomas Marlene , Ujupan Sonia , Vainer Gilad W. , Velthaus Janna-Lisa , André Fabrice
Published: January 2022

Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.