bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of the proposal to regulate lead in hunting ammunition through the European Union’s REACH regulation
Authors: Treu Gabriele , Drost Wiebke , Stock Frauke
Published: May 2020

Background

Despite extensive evidence that exposure to lead from ingested ammunition harms humans and wildlife, and in contravention of European states’ commitments under multilateral environmental agreements to minimize lead emissions, lead in hunting ammunition is still poorly regulated in Europe. The proposed restriction on lead gunshot under the REACH regulation is currently discussed for adoption to protect birds in wetlands from lead poisoning. Based on a subsequent investigation report concluding that additional measures are warranted to control the use of lead ammunition in terrestrial environments, ECHA is preparing a new restriction until October 2020. To help inform this process, we describe REACH management instruments and evaluate the effectiveness and enforceability of different legislative alternatives as well as socio-economic aspects of restricting lead shot in comparison to a total ban. We further discuss how the risks and environmental emissions of lead in rifle bullets can be most effectively controlled by legislative provisions in the future.

Results

Among different management tools, restriction was shown to be most effective and appropriate, since imports of lead ammunition would be covered. The partial restriction of lead gunshot limited to wetlands covers only a minor proportion of all lead used in hunting ammunition in the European Union, leaving multiple wildlife species at risk of being poisoned. Moreover, lead shot will be still purchasable throughout the EU. Within Europe, the costs associated with impacts on wildlife, humans and the environment would be considerably lower when switching to alternative gunshot and rifle bullets.

Conclusion

We argue that there is sufficient evidence to justify more effective, economic, and practical legislative provisions under REACH, i.e., restricting the use and placing on the market of lead in hunting ammunition. The enforcement would be significantly facilitated and hunters could easier comply. A crucial step is to define a realistic phasing-out period and chemical composition standards for non-lead substitutes while engaging all stakeholders to improve acceptance and allow adaptation. Until the total restriction enters into force, Member States could consider imposing more stringent national measures. A total restriction would reduce wildlife poisoning, harmonize provisions of national and European laws, and foster any efforts to decelerate loss of biodiversity.
Occurrence and multiple-level ecological risk assessment of pharmaceuticals and personal care products (PPCPs) in two shallow lakes of China
Authors: Liu Na , Jin Xiaowei , Yan Zheng , Luo Ying , Feng Chenglian , Fu Zhiyou , Tang Zhi , Wu Fengchang , Giesy John P.
Published: May 2020

Background

Management of pharmaceuticals and personal care products (PPCPs) in the environment has become a social issue. In the present study, concentrations of 140 PPCPs at 20 sites in Baiyangdian Lake and Tai Lake from 2016 to 2017 were analyzed by ultra performance liquid chromatography mass spectrometer (UPLC–MS). Risk quotients (RQ) were calculated for each detected chemical at all sites and prioritization indices (PI), based on maximum RQ, were calculated. To assess the risk of chemicals that identified high priority (PI > 1), a more accurate method of joint probability curves (JPCs) was applied.

Results

A total of 42 PPCPs were identified and quantified detected in the two lakes, with maximum concentrations ranging from 0.04 to 889 ng/L. Among these, seven PPCPs were identified as high or moderate-risk pollutants for at least one site, 3 in Tai Lake and 5 in Baiyangdian Lake. Carbamazepine posed significant ecological risk at all 20 sites, such that more attention should be paid to that drug. Based on results of the JPCs, sulfamethoxazole, caffeine, diethyltoluamide, and carbamazepine were categorized as high or intermediate risks.

Conclusion

Occurrences and distributions of PPCPs were different in the two lakes. Multiple-level risk assessment from simple to more complex was appropriate in chemical risk management.
How to coordinate the relationship between renewable energy consumption and green economic development: from the perspective of technological advancement
Authors: Xie Fangming , Liu Yali , Guan Fangyuan , Wang Ning
Published: May 2020

Background

Green economic development refers to reducing pollution emissions and increasing production efficiency while promoting economic growth. Although the renewable energy consumption is “green,” it may not promote green economic development due to the constraints of existing technical conditions. Therefore, the technological advancement approach that can help coordinate the relationship between renewable energy consumption and green economic development should be identified. That is, determining whether to develop new technologies or improve existing technologies should be paid more attention in the context of continuous increase in renewable energy consumption.

Results

(1) The inverted N-shaped relationship between renewable energy consumption and green economic development under the existing technical conditions. The degree of renewable energy consumption can merely promote green economic development in the interval of 0.67–10.87. That is, the renewable energy consumption (% of total energy consumption) is less than 0.67% or greater than 10.87%, which is not conducive to green economic development. (2) Developing new technologies can stimulate the positive effect of renewable energy consumption on green economic development. However, the improvement of existing technologies fails to exhibit an effective impact on the relationship between renewable energy consumption and green economic development. (3) Coordinating the relationship between renewable energy consumption and green economic development can also be achieved by reducing the dependence of Gross Domestic Product (GDP) on fossil fuels. (4) The stage of economic development might impact the effect of renewable energy on green economic development.

Conclusions

It is particularly important to improve technological innovation capabilities, especially in countries with a high proportion of renewable energy consumption. In addition, the government should guide the funds and resources to the renewable energy industry through the credit rationing system to promote the transition of the industrial structure to an environmentally friendly direction. For countries with relatively low levels of economic development, this does not mean that these countries should reduce their demand for renewable energy. Instead, these countries need to take more proactive measures, such as increasing technological innovation capabilities and optimizing industrial structure to coordinate the relationship between renewable energy consumption and green economic development.
Chloroplast (Cp) Transcriptome of P. davidiana Dode×P. bolleana Lauch provides insight into the Cp drought response and Populus Cp phylogeny
Authors: Zhang Xin , Gu Chenrui , Zhang Tianxu , Tong Botong , Zhang Heng , Wu Yueliang , Yang Chuanping
Published: May 2020

Background

Raw second-generation (2G) lignocellulosic biomass materials have the potential for development into a sustainable and renewable source of energy. Poplar is regarded as a promising 2G material (P. davidiana Dode×P. bolleana Lauch, P. bolleana, P. davidiana, P. euphratica, et al). However, their large-scale commercialization still faces many obstacles. For example, drought prevents sufficient irrigation or rainfall, which can reduce soil moisture and eventually destroy the chloroplast, the plant photosynthetic organelle. Heterosis is widely used in the production of drought-tolerant materials, such as the superior clone “Shanxinyang” selected from the offspring of Populus davidiana Dode×Populus bolleana Lauch. Because it produces good wood and is easily genetically transformed, “Shanxinyang” has become a promising material for use in tree genetics. It is also one of the most abundant biofuel plants in northern China. Understanding the genetic features of chloroplasts, the cp transcriptome and physiology is crucial to elucidating the chloroplast drought-response model.

Results

In this study, the whole genome of “Shanxinyang” was sequenced. The chloroplast genome was assembled, and chloroplast structure was analysed and compared with that of other popular plants. Chloroplast transcriptome analysis was performed under drought conditions. The total length of the “Shanxinyang” chloroplast genome was 156,190 bp, the GC content was 36.75%, and the genome was composed of four typical areas (LSC, IRa, IRb, and SSC). A total of 114 simple repeats were detected in the chloroplast genome of “Shanxinyang”. In cp transcriptome analysis, we found 161 up-regulated and 157 down-regulated genes under drought, and 9 cpDEGs was randomly selected to conduct reverse transcription (RT)–qPCR., in which the Log2 (fold change) was significantly consistent with the qPCR results. The analysis of chloroplast transcription under drought provided clues for understanding chloroplast function under drought. The phylogenetic position of “Shanxinyang” within Populus was analysed by using the chloroplast genome sequences of 23 Populus plants, showing that “Shanxinyang” belongs to Sect. Populus and is sister to Populus davidiana. Further, mVISTA analysis showed that the variation in non-coding (regulatory) regions was greater than that in coding regions, which suggests that further attention should be paid to the chloroplast in order to obtain new evolutionary or functional insights related to aspects of plant biology.

Conclusions

Our findings indicate that complex prokaryotic genome regulation occurs when processing transcripts under drought stress. The results not only offer clues for understanding the chloroplast genome and transcription features in woody plants but also serve as a basis for future molecular studies on poplar species.
Omentin-1 is associated with atrial fibrillation in patients with cardiac valve disease
Authors: Chen Yubin , Liu Fen , Han Fei , Lv Lizhi , Tang Can-e , Xie Zhongshang , Luo Fanyan
Published: May 2020

Background

Epicardial adipose tissue (EAT) remodeling and adipocytokines are associated with structural remodeling in atrial fibrillation (AF). However, the role of omentin-1, a novel adipocytokine, in structural remodeling remains unknown.

Methods

Hematoxylin and eosin (H&E) and Masson’s trichrome stains were used to investigate the histology of EAT and right atrial appendages. The expression levels of adipocytokines in these human samples were determined by immunohistochemical assay and western blotting. Models of transforming growth factor (TGF)-β1-induced activation of cardiac fibroblasts (CFs) and TGF-β1-induced endothelial-mesenchymal transition (EndMT) of human umbilical vein endothelial cell (HUVEC) were established to explore roles of omentin-1 in these processes. To determine changes in adipocytokines secretion under hypoxia conditions, adipocytes were treated with 5% O2 and 95% N2, and then CFs and HUVECs were co-cultured with the conditioned medium of adipocytes to determine the effects of hypoxia-treated adipocytes on these cells.

Results

Expression of omentin-1 was downregulated in the EAT and right atrial appendages from patients with AF compared to samples from patients without AF, while the TGF-β1 level was upregulated in EAT from patients with AF. EAT from patients with AF exhibited adipocyte hypertrophy and severe interstitial fibrosis. Omentin-1 inhibited TGF-β1-induced CF activation and reversed TGF-β1-induced HUVEC EndMT. Adipocytes treated with hypoxia exhibited downregulation of omentin-1 and partly activated CFs.

Conclusions

This study demonstrated that omentin-1 was an antifibrotic adipocytokine and was downregulated in patients with AF, which was partly mediated by hypoxia.
Intra-cardiac ultrasound guided approach for catheter ablation of typical right free wall accessory pathways
Authors: Jan Matevž , Kalinšek Tine Prolič , Štublar Jernej , Jelenc Matija , Pernat Andrej , Žižek David , Lakič Nikola
Published: May 2020

Background

Right free wall accessory pathways (AP) are difficult to treat with catheter ablation as ablation catheter (AC) instability at the tricuspid annulus often precludes successful procedure.

The aim of our study was to test a novel intra-cardiac echocardiography (ICE) guided technique for AC placement. Feasibility and success rates were observed.

Methods

Eight consecutive patients (aged 29 ± 21 years, 4 female) with Wolff-Parkinson-White syndrome and a right free wall AP were included in the study. ICE, three-dimensional (3D) electro-anatomic mapping (EAM) system, and a steerable long sheath were used together with either an irrigated or a non-irrigated tip radio-frequency AC to achieve a “loop” manoeuvre which provided AC tip stability at the ventricular aspect of the tricuspid annulus. X-ray fluoroscopy was not used.

Results

Three patients had an anterior and five had a lateral location of the right free wall AP. Procedures were successful in all patients, without recurrences during the mean follow-up of 397 ± 363 days. Average procedural duration was 90 ± 31 min. On average, 6.6 ± 5.7 ablations were needed. Average time to terminate AP conduction after the start of ablation was 4.8 ± 4.2 s. In five patients (62%) AP conduction was successfully terminated with the first ablation. There were no procedural complications.

Conclusions

The novel ICE-guided approach with concomitant use of the steerable sheath and the 3D EAM system for zero-fluoroscopy mapping and ablation of the right free wall APs proved feasible and resulted in excellent acute and long-term outcomes.
Lower maximum forces on oral structures when using gum-elastic bougie than when using endotracheal tube and stylet during both direct and indirect laryngoscopy by novices: a crossover study using a high-fidelity simulator
Authors: Ono Yuko , Shinohara Kazuaki , Shimada Jiro , Inoue Shigeaki , Kotani Joji
Published: May 2020

Background

Applying excessive force during endotracheal intubation (ETI) is associated with several complications, including dental trauma and hemodynamic alterations. A gum-elastic bougie (GEB), a type of tracheal tube introducer, is a useful airway adjunct for patients with poor laryngoscopic views. However, how the use of a GEB affects the force applied during laryngoscopy is unclear. We compared the force applied on the oral structures during ETI performed by novices using the GEB versus an endotracheal tube + stylet.

Methods

This prospective crossover study was conducted from April 2017 to March 2019 in a public medical university in Japan. In total, 209 medical students (4th and 5th grade, mean age of 23.7 ± 2.0 years) without clinical ETI experience were recruited. The participants used either a Macintosh direct laryngoscope (DL) or C-MAC video laryngoscope (VL) in combination with a GEB or stylet to perform ETI on a high-fidelity airway management simulator. The order of the first ETI method was randomized to minimize the learning curve effect. The outcomes of interest were the maximum forces applied on the maxillary incisors and tongue during laryngoscopy. The implanted sensors in the simulator quantified these forces automatically.

Results

The maximum force applied on the maxillary incisors was significantly lower when using a GEB than when using an endotracheal tube + stylet both with the Macintosh DL (39.0 ± 23.3 vs. 47.4 ± 32.6 N, P < 0.001) and C-MAC VL (38.9 ± 18.6 vs. 42.0 ± 22.1 N, P < 0.001). Similarly, the force applied on the tongue was significantly lower when using a GEB than when using an endotracheal tube + stylet both with the Macintosh DL (31.9 ± 20.8 vs. 37.8 ± 22.2 N, P < 0.001) and C-MAC VL (35.2 ± 17.5 vs. 38.4 ± 17.5 N, P < 0.001).

Conclusions

Compared with the use of an endotracheal tube + stylet, the use of a GEB was associated with lower maximum forces on the oral structures during both direct and indirect laryngoscopy performed by novices. Our results suggest the expanded role of a GEB beyond an airway adjunct for difficult airways.
Framing the numerical findings of Cochrane plain language summaries: two randomized controlled trials
Authors: Buljan Ivan , Tokalić Ružica , Roguljić Marija , Zakarija-Grković Irena , Vrdoljak Davorka , Milić Petra , Puljak Livia , Marušić Ana
Published: May 2020

Background

Cochrane systematic review Plain language Summaries (CSR PLSs should serve as a tool for the evidence translation to non-medical population. However, the evidence of optimal type of numerical presentation in CSR PLSs is still scarce. The aim of this study was to investigate readers’ comprehension and preferences for different presentation of findings, including framing and numerical data, in Cochrane systematic review Plain Language Summaries (CSR PLSs).

Methods

We conducted a parallel randomized trial and a crossover randomized trial at the School of Medicine and family practice offices in Split, Croatia. The participants were students and consumers. We assessed possible differences in comprehension, measured by four questions on PLS content, of CSR PLSs depending on the positive or negative framing of results (n = 91) (Trial 1) or using percentages or frequencies for the presentation of results (n = 245) (Trial 2). The outcome measures were comprehension of PLS content, perceived effectiveness of the treatment and readiness to use the treatment (all on 1–10 scales).

Results

In Trial 1 we found no difference in readers’ perception of the effectiveness of the described treatment, desire that the treatment be offered by their family doctor, readiness to use the treatment, or comprehension when CSR PLS results were presented positively or negatively. In Trial 2 we found no difference in CSR PLS comprehension when results were presented as natural frequencies or percentages (BF10 = 0.62, Bayesian t-test for independent samples).

Conclusions

Numerical presentation and framing direction of results appear to have no significant impact on understanding of messages in CSR PLSs.

Trial registration

The trials were registered in ClinicalTrials.gov. Protocol registration numbers: Trial 1: NCT03442387; Trial 2: NCT03554252.
Clinical features in primary care electronic records before diagnosis of ankylosing spondylitis: a nested case-control study
Authors: Bashir Mohammed T. , Iversen Lisa , Burton Christopher
Published: May 2020

Background

Ankylosing spondylitis (AS) often has a long period from first symptom presentation to diagnosis. We examined the occurrence of symptoms, prescriptions and diagnostic tests in primary care electronic records over time prior to a diagnosis of AS.

Methods

Nested case-control study using anonymised primary care electronic health records from Scotland. Cases were 74 adults with a first diagnosis of AS between 2000 and 2010. Controls were matched for age, sex and GP practice: (a) 296 randomly selected adults (b) 169 adults whose records contained codes indicating spinal conditions or symptoms.

We extracted clinical features (symptoms, AS-related disorders, prescriptions and diagnostic tests). Conditional logistic regression was used to examine the association between clinical features (both individually and in combinations) and diagnosis of AS. We examined the associations between clinical features and diagnosis over time prior to diagnosis.

Results

Several new composite pointers were predictive of AS: including distinct episodes of axial pain separated by more than 6 months (OR 12.7, 95% CI 4.7 to 34.6); the occurrence of axial pain with and tendon symptoms within the same year (OR 21.7, 95% CI 2.6 to 181.5); and the co-occurrence (within 30 days) of axial pain and a prescription for nonsteroidal anti-inflammatory drug (OR 10.4, 95%CI 4.9 to 22.1). Coded episodes of axial pain increased steadily over the 3 years before diagnosis. In contrast, large joint symptoms and enthesopathy showed little or no time trend prior to diagnosis.

Conclusions

We identified novel composite pointers to a diagnosis of AS in GP records. These may represent valuable targets for diagnostic support systems.
Lead poisoning; a neglected potential diagnosis in abdominal pain
Authors: Shabani Mahtab , Hadeiy Seyed Kaveh , Parhizgar Parinaz , Zamani Nasim , Mehrad Hamid , Hassanian-Moghaddam Hossein , Phillips Scott
Published: May 2020

Background

Abdominal pain may be a presenting symptom of lead poisoning and is often difficult to diagnose. This study aimed to determine the prevalence of abdominal pain in patients seen in the Laghman Hakim Hospital ED and GI clinic who were lead-intoxicated, with or without opiate use disorder.

Methods

Between July 2017 and January 2018, patients seen in the ED and GI clinic of Loghman Hakim Hospital with unexplained abdominal pain or abdominal pain resistant to treatment were enrolled. Informed consent was obtained from potential enrollees. For standardization, a pre-designed data collection tool was developed for uniform data acquisition. Opiate use was determined historically. For this study, lead poisoning was defined as a blood lead level (BLL) greater than or equal to 30 μg/dL (1.45 μmol/L) with concomitant GI symptoms.

Results

Of 125 patients admitted, 28 (22.4%) had BLLs higher than 30 μg/dL. None of the patients had signs and symptoms of opioid withdrawal syndrome during evaluation. Elevated BLLs were significantly correlated with oral opium use/abuse, history of addiction for over the preceding 12 years. The daily opium use was more than 2.75 g. There was a statistical correlation between lead toxicity and abdominal pain consistency and intensity, constipation, and paresthesias. Anemia, leukocytosis, and abnormal liver enzyme tests were laboratory findings associated with lead toxicity. Four patients died, one of whom was diagnosed with lead toxicity.

Conclusion

Lead toxicity should be considered in the potential differential diagnosis of severe and resistant abdominal pain in patients referring to general EDs or GI clinics if a positive history of opium abuse exists.
Exosomal miRNA signatures of pancreatic lesions
Authors: Vicentini Caterina , Calore Federica , Nigita Giovanni , Fadda Paolo , Simbolo Michele , Sperandio Nicola , Luchini Claudio , Lawlor Rita T. , Croce Carlo Maria , Corbo Vincenzo , Fassan Matteo , Scarpa Aldo
Published: May 2020

Background

Pancreatic and peri-pancreatic neoplasms encompass a variety of histotypes characterized by a heterogeneous prognostic impact. miRNAs are considered efficient candidate biomarkers due to their high stability in tissues and body fluids. We applied Nanostring profiling of circulating exosomal miRNAs to distinct pancreatic lesions in order to establish a source for biomarker development.

Methods

A series of 140 plasma samples obtained from patients affected by pancreatic ductal adenocarcinoma (PDAC, n = 58), pancreatic neuroendocrine tumors (PanNET, n = 42), intraductal papillary mucinous neoplasms (IPMN, n = 20), and ampulla of Vater carcinomas (AVC, n = 20) were analyzed. Comprehensive miRNA profiling was performed on plasma-derived exosomes. Relevant miRNAs were validated by qRT-PCR and in situ hybridization (ISH).

Results

Lesion specific miRNAs were identified through multiple disease comparisons. Selected miRNAs were validated in the plasma by qRT-PCR and at tissue level by ISH. We leveraged the presence of clinical subtypes with each disease cohort to identify miRNAs that are differentially enriched in aggressive phenotypes.

Conclusions

This study shows that pancreatic lesions are characterized by specific exosomal-miRNA signatures. We also provide the basis for further explorations in order to better understand the relevance of these signatures in pancreatic neoplasms.
Sensor-based characterization of daily walking: a new paradigm in pre-frailty/frailty assessment
Authors: Pradeep Kumar Danya , Toosizadeh Nima , Mohler Jane , Ehsani Hossein , Mannier Cassidy , Laksari Kaveh
Published: May 2020

Background

Frailty is a highly recognized geriatric syndrome resulting in decline in reserve across multiple physiological systems. Impaired physical function is one of the major indicators of frailty. The goal of this study was to evaluate an algorithm that discriminates between frailty groups (non-frail and pre-frail/frail) based on gait performance parameters derived from unsupervised daily physical activity (DPA).

Methods

DPA was acquired for 48 h from older adults (≥65 years) using a tri-axial accelerometer motion-sensor. Continuous bouts of walking for 20s, 30s, 40s, 50s and 60s without pauses were identified from acceleration data. These were then used to extract qualitative measures (gait variability, gait asymmetry, and gait irregularity) and quantitative measures (total continuous walking duration and maximum number of continuous steps) to characterize gait performance. Association between frailty and gait performance parameters was assessed using multinomial logistic models with frailty as the dependent variable, and gait performance parameters along with demographic parameters as independent variables.

Results

One hundred twenty-six older adults (44 non-frail, 60 pre-frail, and 22 frail, based on the Fried index) were recruited. Step- and stride-times, frequency domain gait variability, and continuous walking quantitative measures were significantly different between non-frail and pre-frail/frail groups (p < 0.05). Among the five different durations (20s, 30s, 40s, 50s and 60s), gait performance parameters extracted from 60s continuous walks provided the best frailty assessment results. Using the 60s gait performance parameters in the logistic model, pre-frail/frail group (vs. non-frail) was identified with 76.8% sensitivity and 80% specificity.

Discussion

Everyday walking characteristics were found to be associated with frailty. Along with quantitative measures of physical activity, qualitative measures are critical elements representing the early stages of frailty. In-home gait assessment offers an opportunity to screen for and monitor frailty.

Trial registration

The clinical trial was retrospectively registered on June 18th, 2013 with ClinicalTrials.gov, identifier NCT01880229.
Scrub typhus as a rare cause of acute pyelonephritis: case report
Authors: Bhattarai Tulsi , Poudel Sujan Chandra , Pokharel Nishma , Bhattarai Suraj
Published: May 2020

Background

Scrub typhus can present with atypical signs and symptoms such as those of acute kidney injury, gastroenteritis, pneumonitis, and acute respiratory distress syndrome. Meningitis, encephalitis, and hepatic dysfunction have also been reported, particularly in severe cases with multisystem involvement. Scrub typhus has never been reported in the literature to cause urinary tract infections (UTIs) which includes cystitis and pyelonephritis.

Case presentation

A 45-year old male presenting to the outpatient unit with fever, right flank pain, and burning micturition for three days was initially treated for UTI. However, he returned to the hospital on the fourth day of illness with persistent symptoms. He was hospitalized, with intravenous (IV) ceftriaxone. Computerized tomography scan of his abdomen-pelvis showed features of acute pyelonephritis, so his antibiotics were upgraded to meropenem and teicoplanin. Despite this, the patient’s condition deteriorated. Laboratory investigations showed multisystem involvement: decreasing platelets, raised creatinine, and deranged liver panel. As Kathmandu was hit by dengue epidemic during the patient’s hospitalization, on the seventh day of his illness, blood samples were sent for tropical fever investigation. All tests came out negative except for scrub typhus—IgM antibodies positive on rapid diagnostic test. The patient’s symptoms subsided after 48 h of starting doxycycline and he became fully asymptomatic four days later. Fever did not recur even after discontinuing other IV antibiotics, favoring scrub typhus disease rather than systemic bacterial sepsis.

Conclusions

Scrub typhus is an emerging infectious disease of Nepal. Therefore, every unexplained fever cases (irrespective of clinical presentation) should be evaluated for potential Rickettsiosis. Moreover, for cases with acute pyelonephritis, atypical causative agents should be investigated, for example scrub typhus in this case.
Concurrent pathogenic variants in SLC6A1/NOTCH1/PRIMPOL genes in a Chinese patient with myoclonic-atonic epilepsy, mild aortic valve stenosis and high myopia
Authors: Yuan Haiming , Wang Qingming , Li Yufeng , Cheng Shuangxi , Liu Jianxin , Liu Yanhui
Published: May 2020

Background

Pathogenic SLC6A1 variants have been reported in patients with myoclonic-atonic epilepsy (MAE). NOTCH1, encoding a member of the Notch family of proteins, is known to be associated with aortic valve disease. The PRIMPOL variant has only been identified in Chinese patients with high myopia. Exome sequencing analysis now allows the simultaneous detection of multiple genetic etiologies for patients with complicated clinical features. However, the presence of three Mendelian disorders in one patient supported by their respective pathogenic variants and clinical phenotypes is very rare.

Case presentation

Here, we report a 4-year-old Chinese boy who presented with MAE, delayed language, borderline intellectual disability (ID), mildly impaired social skills and attention deficit hyperactivity disorder (ADHD). He also had mild aortic valve stenosis and high myopia. Using whole-exome sequencing (WES), we identified three variants: (1) SLC6A1, NM_003042.4: c.881-883del (p.Phe294del), (2) NOTCH1, NM_017617.5:c.1100-2A > G and (3) PRIMPOL, NM_152683.4:c.265 T > G (p.Tyr89Asp). Parental Sanger sequencing confirmed that SLC6A1 and NOTCH1 variants were de novo, whereas the PRIMPOL variant was inherited from the father who also had high myopia. Furthermore, the PRIMPOL variant was absent from the genomes of the paternal grandparents, and thus was also a de novo event in the family. All three variants are classified as pathogenic.

Conclusion

The SLC6A1 variant could explain the features of MAE, delayed language, borderline ID, impaired social skills and ADHD in this patient, whereas the features of aortic valve stenosis and high myopia of the patient may be explained by variants in NOTCH1 and PRIMPOL, respectively. This case demonstrated the utility of exome sequencing in uncovering the multiple pathogenic variants in a patient with complicated phenotypes due to the blending of three Mendelian disorders.
Clinical validation of full genotyping CLART® HPV4S assay on SurePath and ThinPrep collected screening samples according to the international guidelines for human papillomavirus test requirements for cervical screening
Authors: Ejegod Ditte Møller , Lagheden Camilla , Bhatia Ramya , Pedersen Helle , Boada Elia Alcañiz , Sundström Karin , Cortés Javier , Josë F. Xavier Bosch , Cuschieri Kate , Dillner Joakim , Bonde Jesper
Published: May 2020

Background

To ensure the highest quality of human papillomavirus (HPV) testing in primary cervical cancer screening, novel HPV assays must be evaluated in accordance with the international guidelines. Furthermore, HPV assay with genotyping capabilities are becoming increasingly important in triage of HPV positive women in primary HPV screening. Here we evaluate a full genotyping HPV assay intended for primary screening.

Methods

The CLART® HPV4S (CLART4S) assay is a newly developed full-genotyping assay detecting 14 oncogenic (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) and two non-oncogenic HPV genotypes (6, 11). It was evaluated using SurePath and ThinPrep screening samples collected from the Danish and Swedish cervical cancer screening programs, respectively. For calculation of sensitivity, 81 SurePath and 80 ThinPrep samples with confirmed ≥CIN2 were assessed. For clinical specificity analysis, 1184 SurePath and 1169 ThinPrep samples from women with <CIN2 histology were assessed. Sensitivity and specificity of the CLART4S assay was compared to an established reference test; the MGP-PCR (Modified General Primers GP5+/6+ with genotyping using Luminex). Inter and intra laboratory reproducibility of the assay was assessed using 540 SurePath and 520 ThinPrep samples, respectively. The genotype concordance between CLART4S and MGP-PCR was also assessed.

Results

In SurePath samples, the sensitivity of CLART4S was 0.90 (MGP-PCR =0.93) and the specificity was 0.91 (MGP-PCR = 0.91); In ThinPrep samples the sensitivity of CLART4S was 0.98 (MGP-PCR = 1.00) and specificity was 0.94 (MGP-PCR =0.87). The CLART4S was shown to be non-inferior to that of MGP-PCR for both sensitivity (p = 0.002; p = 0.01) and specificity (p = 0.01; p = 0.00) in SurePath and ThinPrep samples, respectively. Intra-laboratory reproducibility and inter-laboratory agreement was met for both media types. The individual genotype concordance between CLART4S and MGP-PCR was good agreement for almost all 14 HPV genotypes in both media types.

Conclusions

The CLART4S assay was proved non-inferior to the comparator assay MGP-PCR for both sensitivity and specificity using SurePath and ThinPrep cervical cancer screening samples from the Danish and Swedish screening programs, respectively. This is the first study to demonstrate clinical validation of a full-genotyping HPV assay conducted in parallel on both SurePath and ThinPrep collected samples.
Bis-benzylidine Piperidone RA190 treatment of hepatocellular carcinoma via binding RPN13 and inhibiting NF-κB signaling
Authors: Soong Ruey-Shyang , Anchoori Ravi K. , Roden Richard B. S. , Cho Rou-Ling , Chen Yi-Chan , Tseng Sheng-Chieh , Huang Yun-Li , Liao Po-Cheng , Shyu Yu-Chiau
Published: May 2020

Background

According to GLOBOSCAN, hepatocellular carcinoma (HCC) claimed 782,000 lives in 2018. The tyrosine kinase inhibitor sofafenib is used to treat HCC, but new anticancer agents targeting different pathways are urgently needed to improve outcomes for patients with advanced disease. The aberrant metabolism and aggressive growth of cancer cells can render them particularly susceptible to proteasome inhibition, as demonstrated by bortezomib treatment of multiple myeloma. However, resistance does emerge, and this 20S proteasome inhibitor has not proven active against HCC. The bis-benzylidine piperidone RA190 represents a novel class of proteasome inhibitor that covalently binds to cysteine 88 of RPN13, an ubiquitin receptor subunit of the proteasome’s 19S regulatory particle. RA190 treatment inhibits proteasome function, causing rapid accumulation of polyubiquitinated proteins. Considerable evidence suggests that nuclear factor κB (NF-κB) signaling, which is dependent upon the proteasome, is a major driver of inflammation-associated cancers, including HCC.

Methods

Human HCC cell lines were treated with titrations of RA190. The time course of endoplasmic reticulum stress and NF-κB-related mechanisms by which RA190 may trigger apoptosis were assessed. The therapeutic activity of RA190 was also determined in an orthotopic HCC xenograft mouse model.

Results

RA190 is toxic to HCC cells and synergizes with sofafenib. RA190 triggers rapid accumulation of polyubiquitinated proteins, unresolved endoplasmic reticulum stress, and cell death via apoptosis. RA190 blocks proteasomal degradation of IκBα and consequent release of NF-κB into the nuclei of HCC cells. Treatment of mice bearing an orthotopic HCC model with RA190 significantly reduced tumor growth.

Conclusions

RA190 has therapeutic activity in a xenograft model, and with sorafenib exhibited synergetic killing of HCC cells in vitro, suggesting further exploration of such a combination treatment of HCC is warranted.
Glistening formation in a new hydrophobic acrylic intraocular lens
Authors: Yildirim Timur M. , Fang Hui , Schickhardt Sonja K. , Wang Qiang , Merz Patrick R. , Auffarth Gerd U.
Published: May 2020

Background

The formation of fluid-filled microvacuoles, termed glistenings, is a common complication of intraocular lenses (IOLs) made from hydrophobic acrylate. Using our well-established in-vitro laboratory method, we evaluated a new IOL material’s resistance to glistening formation.

Methods

An in-vitro stress test for glistening induction was performed on 20 samples of hydrophobic acrylic IOLs: ten of the new Eyecryl ASHFY600 (Biotech Vision Care, Ahmedabad, India) compared with ten samples of AcrySof IQ SN60WF (Alcon, Fort Worth, USA). The number of microvacuoles per square millimetre (MV/mm2) was evaluated in five sections of each IOL. The results for each model were compared and rated on a modified Miyata Scale for grading glistening severity.

Results

In all cases, glistening number was higher in the central section of the IOL optic than in the periphery. Mean number of MV/mm2 was highest in the central part of the AcrySof IQ SN60WF, with 41.84 (±27.67) MVs/mm2. The lowest number of glistenings was found in the five sections of the Eyecryl ASHFY600 with 0.52 (±0.24) MVs/mm2. Mean value of the Eyecryl ASHFY600 IOL, using the Miyata Scale, was Zero.

Conclusion

In this in-vitro laboratory study, the new hydrophobic acrylic IOL showed a high resistance to microvacuole formation. Results from this in-vitro study suggest that glistening numbers will be low in clinical use in the Eyecryl ASHFY600.
Characteristics and treatments of ocular blast injury in Tianjin explosion in China
Authors: Liu Yuanyuan , Feng Kang , Jiang Hao , Hu Fuhua , Gao Jun , Zhang Wanhong , Zhang Wenjing , Huang Bo , Brant Rodrigo , Zhang Cheng , Yan Hua
Published: May 2020

Background

To document characteristics and treatments of ocular blast injury from a fire and explosion.

Method

Authors retrospectively evaluated 116 patients with 166 eye injuries from six hospitals. Terminology of ocular injury referred to Birmingham Eye Trauma Terminology, and best-corrected visual acuity (BCVA) was categorized with the ocular trauma score (OTS) grading system. Incidence, preoperational and follow-up BCVA, treatment of severe ocular blast injuries were surveyed.

Results

Oculoplastic injuries accounted for the majority of eye injuries, while globe injuries were presented in 52 eyes with median baseline OTS 70 ranging from 26 to 100. No endophthalmitis occurred. The mean timing of the first-stage operations was 9.4 ± 6.4 h after blast, while second-stage operations were performed on average 14.7 ± 0.9 days post blast. Final BCVA of 68.8% of eyes achieved 20/200 or better as followed, 7 open globe injuries had a BCVA of no light perception. Additionally, eyes presenting rupture, retinal detachment, vitreous hemorrhage, choroidal injury and initial BCVA less than 20/200 had worse final visual outcomes, while globe penetration was not associated with poor visual acuity.

Conclusion

Various ocular injuries were commonly in the casualties of blast, in which open-globe injuries have worst visual prognosis. OTS is a valid approach for evaluation of prognosis and optimizing the therapeutic strategies subsequently in the massive casualty. Intense rescue and careful examination, proper surgery should be performed correctly to rescue patients.
Effect of 1.8-mm steep-axis clear corneal incision on the posterior corneal astigmatism in candidates for toric IOL implantation
Authors: Li Xi , Chen Xiang , He Suhong , Xu Wen
Published: May 2020

Background

In the present study, we aimed to analyze the effects of cataract surgery using a 1.8-mm steep-axis clear corneal incision (CCI) on the posterior corneal surfaces based on the keratometry from the rotating Scheimpflug imaging device (Pentacam HR) in candidates for toric intraocular lens (IOL) implantation.

Methods

Preoperative and at least 1-month postoperative data measured by Pentacam HR were collected in patients for toric IOL implantation. Surgically induced astigmatism on the posterior cornea (P-SIA) was calculated based on the preoperative and postoperative keratometric data, and the related factors of P-SIA were analyzed.

Results

A total of 60 eyes from 56 patients were enrolled. The preoperative anterior, posterior and total corneal astigmatism was 1.58 ± 0.61 D,0.28 ± 0.22 D and 1.70 ± 0.52 D respectively. The postoperative anterior, posterior and total corneal astigmatism was 1.26 ± 0.68 D, 0.41 ± 0.26 D and 1.30 ± 0.51 D respectively. The astigmatism was significantly decreased on anterior surface (P<0.001, paired t-test) and increased on posterior surface (P<0.001, paired t-test). The mean of P-SIA calculated by Holladay–Cravy–Koch method was 0.34 ± 0.20 D, with 0.5 D or greater accounting for 26.7%. A statistically significant correlation was observed between the P-SIA and preoperative anterior corneal astigmatism (r = 0.29, P = 0.024), as well as preoperative posterior corneal astigmatism (r = 0.27, P = 0.038). Multivariate regression analysis showed the preoperative anterior and posterior corneal astigmatism had a significant effect on P-SIA (F = 7.344, P = 0.001).

Conclusions

In candidates for toric IOL implantation with a 1.8-mm steep-axis CCI, the incision caused a significant reduction of the anterior corneal astigmatism but an increase of the posterior corneal astigmatism. P-SIA could not be ignored, and it played a significant role in SIA, especially in cases with higher preoperative anterior or posterior corneal astigmatism.
Factors and predictors of length of stay in offenders diagnosed with schizophrenia - a machine-learning-based approach
Authors: Kirchebner Johannes , Günther Moritz Philipp , Sonnweber Martina , King Alice , Lau Steffen
Published: May 2020

Background

Prolonged forensic psychiatric hospitalizations have raised ethical, economic, and clinical concerns. Due to the confounded nature of factors affecting length of stay of psychiatric offender patients, prior research has called for the application of a new statistical methodology better accommodating this data structure. The present study attempts to investigate factors contributing to long-term hospitalization of schizophrenic offenders referred to a Swiss forensic institution, using machine learning algorithms that are better suited than conventional methods to detect nonlinear dependencies between variables.

Methods

In this retrospective file and registry study, multidisciplinary notes of 143 schizophrenic offenders were reviewed using a structured protocol on patients’ characteristics, criminal and medical history and course of treatment. Via a forward selection procedure, the most influential factors for length of stay were preselected. Machine learning algorithms then identified the most efficient model for predicting length-of-stay.

Results

Two factors have been identified as being particularly influential for a prolonged forensic hospital stay, both of which are related to aspects of the index offense, namely (attempted) homicide and the extent of the victim’s injury. The results are discussed in light of previous research on this topic.

Conclusions

In this study, length of stay was determined by legal considerations, but not by factors that can be influenced therapeutically. Results emphasize that forensic risk assessments should be based on different evaluation criteria and not merely on legal aspects.
Florida neighborhood analysis of social determinants and their relationship to life expectancy
Authors: Melix Bertram L. , Uejio Christopher K. , Kintziger Kristina W. , Reid Keshia , Duclos Chris , Jordan Melissa M. , Holmes Tisha , Joiner Jessica
Published: May 2020

Background

Social determinants of health (SDOH) contribute to unequal life expectancy (LE). Only a handful of papers have analyzed these relationships at the neighborhood level as opposed to the county level. This study draws on both the SDOH and social vulnerability literature to identify relevant factors affecting LE.

Methods

LE was calculated from mortality records for Florida from 2009 to 2013 for 3640 census tracts with reliable estimates. A spatial Durbin error model (SDEM) quantified the direction and magnitude of the factors to LE. The SDEM contains a spatial error term and jointly estimates both local and neighborhood associations. This methodology controls for non-independence between census tracts to provide unbiased statistical estimates.

Results

Factors significantly related to an increase in LE, include percentage (%) of the population who identify as Hispanic (beta coefficient [β]: 0.06, p-value [P] < 0.001) and % of age dependent populations (% population < 5 years old and % population > 65) (β: 0.13, P < 0.001). Conversely, the following factors exhibited significant negative LE associations, % of households with no automobile (β: -0.05, P < 0.001), % of mobile homes (β: -0.02, P < 0.001), and % of female headed households (β: -0.11, P < 0.001).

Conclusions

Results from the SDEM demonstrate social vulnerability indicators account for additional geographic LE variability beyond commonly studied SDOH. Empirical findings from this analysis can help local health departments identify drivers of spatial health disparities at the local level.
Determinants of fatal car accident risk in Finote Selam town, Northwest Ethiopia
Authors: Tadege Melaku
Published: May 2020

Background

In the globe, 1.3 million deaths and around 50 million non-fatal injuries were reported. From all deaths, 90% occur in developing countries. Ethiopia is considered as one of the worst countries in the globe where road traffic accident causes a lot of fatalities and injuries of road users every year. The main objective of the study was to identify the main predictors of fatal car accident.

Methods

The retrospective research design was applied. 255 records were taken from Finote Selam traffic police office, northwest part of Ethiopia from September 2009 to January 2018. The statistical analysis was performed by using SPSS version 23 software. Chi-square for association test and ordinal logistic regression for predictor identification were used.

Results

Age of drivers were the responsible causes of fatal road traffic accident (p-value = 0.033). The more experienced drivers decreased the occurrence of fatal traffic accidents. In addition, increasing vehicle service year reduced the occurrence of accidental death. Besides, the occurrence of fatal car accident in autumn season was 0.44 times less than that of in summer season. Additionally, drivers’ educational level was played a crucial role in a road traffic accident. For instance, drivers whose educational level was below 12th grade were the most responsible factor for car accident deaths. What is more, it was seen that drivers who drove their vehicles could minimize the occurrence of fatal traffic accident (p-value = 0.010).

Conclusion

In conclusion, fatal road traffic accidents happened due to drivers’ lack of sufficient driving experience and low educational level. In addition, driving on weekends and driving on summer season were disclosed as responsible for fatal car accident. Moreover, drivers with younger age and those who drove a new vehicle likely caused fatal car accident. However, drivers who drive their vehicles seemed to be less responsible for fatal car accident than that of employed.