bluuebunny/crossref_metadata_2025 huggingface dataset:
ProbSevere LightningCast: A Deep-Learning Model for Satellite-Based Lightning Nowcasting
Authors: Cintineo John L. , Pavolonis Michael J. , Sieglaff Justin M.
Published: May 2022

Lightning strikes pose a hazard to human life and property, and can be difficult to forecast in a timely manner. In this study, a satellite-based machine learning model was developed to provide objective, short-term, location-specific probabilistic guidance for next-hour lightning activity. Using a convolutional neural network architecture designed for semantic segmentation, the model was trained using GOES-16 visible, shortwave infrared, and longwave infrared bands from the Advanced Baseline Imager (ABI). Next-hour GOES-16 Geostationary Lightning Mapper data were used as the truth or target data. The model, known as LightningCast, was trained over the GOES-16 ABI contiguous United States (CONUS) domain. However, the model is shown to generalize to GOES-16 full disk regions that are outside of the CONUS. LightningCast provides predictions for developing and advecting storms, regardless of solar illumination and meteorological conditions. LightningCast, which frequently provides 20 min or more of lead time to new lightning activity, learned salient features consistent with the scientific understanding of the relationships between lightning and satellite imagery interpretation. We also demonstrate that despite being trained on data from a single geostationary satellite domain (GOES-East), the model can be applied to other satellites (e.g., GOES-West) with comparable specifications and without substantial degradation in performance. LightningCast objectively transforms large volumes of satellite imagery into objective, actionable information. Potential application areas are also highlighted.

Significance Statement

The outcome of this research is a model that spatially forecasts lightning occurrence in a 0–60-min time window, using only images of clouds from the GOES-R Advanced Baseline Imager. This model has the potential to provide early alerts for developing and approaching hazardous conditions.
Lifetime medical costs attributable to sickle cell disease among nonelderly individuals with commercial insurance
Authors: Johnson Kate M. , Jiao Boshen , Ramsey Scott D. , Bender M. A. , Devine Beth , Basu Anirban
Published: May 2022

Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity, mortality, and a disproportionate burden on Black and Hispanic communities. Our objective was to estimate the total healthcare costs and out-of-pocket (OOP) costs attributable to SCD among commercially insured individuals over their nonelderly lifetimes (0 to 64 years of age). We constructed a retrospective cohort of individuals with diagnosed SCD using Truven Health Marketscan commercial claims data from 2007 through 2018, compared with matched control subjects from the Medical Expenditure Panel Survey. We estimated Kaplan-Meier sample average costs using previously reported survival curves for SCD and control subjects. Individuals with SCD (20 891) and control subjects (33 588) were included in our analysis. The SCD sample had a mean age of 25.7 (standard deviation, 17.4) years; 58.0% were female. Survival-adjusted costs of SCD peaked at age 13 to 24 years and declined at older ages. There was no significant difference in total medical costs or OOP costs between the sexes. SCD-attributable costs over 0 to 64 years of age were estimated to be $1.6 million (95% confidence interval [CI], $1.3M-$1.9M) and $1.7 million (95% CI, $1.4M-$2.1M) for females and males with SCD, respectively. The corresponding OOP estimates were $42 395 (95% CI, $34 756-$50 033) for females and $45 091 (95% CI, $36 491-$53 691) for males. These represent a 907% and 285% increase in total medical and OOP costs over control subjects, respectively. Although limited to the commercially insured population, these results indicate that the direct economic burden of SCD is substantial and peaks at younger ages, suggesting the need for curative and new medical therapies.
Radio communication-based method for analysis of train driving in an ERTMS signaling environment
Authors: Rosberg Tomas , Thorslund Birgitta
Published: May 2022

Background

ERTMS is an important project improving cross-border interoperability throughout Europe by a single rail signaling standard. One advantage following this development is a standardized radio signaling, which can be tracked by logging the data transfer using the ETCS protocol between Radio Block Center and train. This means that a broad spectrum of train driving can be analyzed in terms of for example driving behavior, signal planning and capacity in a new efficient way.

Methods

In this paper a radio-based protocol method to achieve this, is presented and applied for studying braking characteristics in terms of meeting point design. The aim was to design, apply and validate a radio-based train data collection method to enable cost-efficient and avoid time-consuming train data collections. To enable comparison between the results from the suggested radio-based method and traditional methods, a verification measurement was performed. Three different alternatives of speed calculation were validated. These were based on: Train Position Report speed; calculation of average speed based on reported train position; processed reported train position forming the average speed. The best alternative was then applied to examine deceleration towards different signal targets at single-track meeting points.

Results

The results from this study suggest that the ETCS Level 2 protocol is a feasible way to collect train dynamics data. The method is time saving when it comes to train driver behavior studies where several trains and drivers are needed to get significant results. Comparison with traditional GPS method suggest that the method is valid. Most promising is the alternative using processed train position.
Nanocluster-mediated photothermia improves eradication efficiency and antibiotic sensitivity of Helicobacter pylori
Authors: Meng Fansen , Tao Hongjin , Mi Yan , Yang Tianyu , Wang Xuanping , Go Yuyo , Lin Yunjuan , Wang Gangshi
Published: May 2022

Background

Helicobacter pylori (H. pylori) eradication plays a crucial role in gastric cancer prevention, but the antimicrobial resistance of H. pylori is obstructing this elimination process. In this study, we developed nanoclusters (NCs) from Zn0.3Fe2.7O4 nanoparticles using a poly(ethylene glycol)-b-poly(ε-caprolactone)-based nanocarrier as an innovative antibiotic-independent H. pylori management.

Results

The nanocluster showed minimal toxicity and maximal biocompatibility. With a low concentration (50 µg/mL) of NCs under a short time period (~ 2 min) of near-infrared (808 nm) irradiation, we kept the culture medium temperature to 41 °C for 20 min with continuous irradiation. The heated NCs exhibited efficient photothermal effects and resulted in an excellent inhibition of H. pylori growth, adhesion and ability to induce vacuolization in eukaryotic cells in in vitro investigation. Transmission electron microscopy showed a dramatic morphologic change after NCs photothermia on H. pylori, including cell wall and membrane rupture, as well as ribosome damage. Besides, levofloxacin and clarithromycin resistance was decreased after photothermal treatment in H. pylori NCTC 11637 and/or clinical strains, however metronidazole resistance was unchanged. We also discovered a significant decrease in the biofilm formation of H. pylori under the NCs-based photothermal application, while efflux pump function was unchanged.

Conclusions

Based on this novel NCs-based photothermal approach, we were able to demonstrate in vitro a significant inhibition of both H. pylori growth and molecular toxicity, and its improvement in antibiotic sensitivity alone with the eradication of H. pylori biofilms previously believed to be tolerant to conventional antibiotics.
A qualitative assessment of medical assistant professional aspirations and their alignment with career ladders across three institutions
Authors: Vilendrer Stacie , Amano Alexis , Johnson Cati Brown , Morrison Timothy , Asch Steve
Published: May 2022

Background

Growing demand for medical assistants (MAs) in team-based primary care has led health systems to explore career ladders based on expanded MA responsibilities as a solution to improve MA recruitment and retention. However, the practical implementation of career ladders remains a challenge for many health systems. In this study, we aim to understand MA career aspirations and their alignment with available advancement opportunities.

Methods

Semi-structured focus groups were conducted August to December 2019 in primary care clinics based in three health systems in California and Utah. MA perspectives of career aspirations and their alignment with existing career ladders were discussed, recorded, and qualitatively analyzed.

Results

Ten focus groups conducted with 59 participants revealed three major themes: mixed perceptions of expanded MA roles with concern over increased responsibility without commensurate increase in pay; divergent career aspirations among MAs not addressed by existing career ladders; and career ladder implementation challenges including opaque advancement requirements and lack of consistency across practice settings.

Conclusion

MAs held positive perceptions of career ladders in theory, yet recommended a number of improvements to their practical implementation across three institutions including improving clarity and consistency around requirements for advancement and matching compensation to job responsibilities. The emergence of two distinct clusters of MA professional needs and desires suggests an opportunity to further optimize career ladders to provide tailored support to MAs in order to strengthen the healthcare workforce and talent pipeline.
Prescription opioids among older adults: ten years of data across five countries
Authors: Hamina A. , Muller A. E. , Clausen T. , Skurtveit S. , Hesse M. , Tjagvad C. , Thylstrup B. , Odsbu I. , Zoega H. , Jónsdóttir H. L. , Taipale H.
Published: May 2022

Background

Opioid use has increased globally in the recent decade. Although pain remains a significant problem among older adults, susceptibility to opioid-related harms highlights the importance of careful opioid therapy monitoring on individual and societal levels. We aimed to describe the trends of prescription opioid utilisation among residents aged ≥65 in all Nordic countries during 2009–2018.

Methods

We conducted cross-sectional measurements of opioid utilisation in 2009–2018 from nationwide registers of dispensed drugs in Denmark, Finland, Iceland, Norway, and Sweden. The measures included annual opioid prevalence, defined daily doses (DDDs) per 1000 inhabitants per day (DIDs), and morphine milligram equivalents (MMEs) per user per day.

Results

From 2009 to 2018, an average of 808,584 of adults aged ≥65 used opioids yearly in all five countries; an average annual prevalence of 17.0%. During this time period, the prevalence decreased in Denmark, Norway, and Sweden due to declining codeine and/or tramadol use. Iceland had the highest opioid prevalence in 2009 (30.2%), increasing to 31.7% in 2018. In the same period, DIDs decreased in all five countries, and ranged from 28.3 in Finland to 58.5 in Denmark in 2009, and from 23.0 in Finland to 54.6 in Iceland in 2018. MMEs/user/day ranged from 4.4 in Iceland to 19.6 in Denmark in 2009, and from 4.6 in Iceland to 18.8 in Denmark in 2018. In Finland, Norway, and Sweden, MMEs/user/day increased from 2009 to 2018, mainly due to increasing oxycodone utilisation.

Conclusions

The stable or decreasing opioid utilisation prevalence among a majority of older adults across the Nordic countries coincides with an increase in treatment intensity in 2009–2018. We found large cross-national differences despite similarities across the countries’ cultures and healthcare systems. For the aged population, national efforts should be placed on improving pain management and monitoring future trends of especially oxycodone utilisation.
Clinical significance of Mycoplasma pneumoniae specific IgM titer in children hospitalized with Mycoplasma pneumoniae pneumonia
Authors: Choo Soojeong , Kim Seo-Hee , Lee Eun
Published: May 2022

Background

The present study aimed to identify the clinical significance of Mycoplasma pneumoniae (MP)-specific immunoglobulin M (IgM) titer, in addition to a diagnosis of MP infection, in children with MP pneumonia.

Methods

This study was performed in 155 children hospitalized with MP pneumonia. The clinical features and laboratory and radiographic findings on admission in children with positive or negative MP-specific IgM titers were retrospectively reviewed from the electronic medical records.

Results

The mean age of the included children was 6.0 years, and 118 (76.1%) of the children were positive for MP-specific IgM. A longer duration between symptom onset and admission (adjusted odds ratio [aOR] 1.47, 95% confidence interval [CI] 1.24–1.75), longer duration of symptoms during the illness (aOR 1.15, 95% CI 1.02–1.30), and development of extra-pulmonary manifestations (aOR 9.16, 95% CI 1.96–42.81) were significantly associated with a positive MP-specific IgM titer. Serum lactate dehydrogenase levels (aOR 1.00, 95% CI 1.00–1.01) and pneumonic infiltration involving > 50% of the total lung volume on chest radiography (aOR 4.68, 95% CI 1.12–19.55) were associated with positive MP-specific IgM in children with MP pneumonia. A poor response to stepwise treatment for MP pneumonia was more common in children with a positive MP-specific IgM titer than those with a negative MP-specific IgM titer on admission.

Conclusions

A positive MP-specific IgM titer at diagnosis of MP pneumonia may partially suggest an exaggerated immune response with a higher disease burden compared to children with MP pneumonia with a negative MP-specific IgM titer.
Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations
Authors: Chen Jiannan , Zhao Zhe , Shen Hongrui , Bing Qi , Li Nan , Guo Xuan , Hu Jing
Published: May 2022

Background

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. However, the clinical sign of spastic paraplegia can also be seen in a variety of hereditary neurologic diseases with bilateral corticospinal tract impairment. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis.

Methods

Twenty-seven cases were screened out to have definite or suspected pathogenic variants from clinically suspected HSP pedigrees through HSP-associated sequencing and/or expanded genetic testing. One case was performed for enzyme detection of leukodystrophy without next-generation sequencing. In addition, detailed clinical, laboratorial, electrophysiological and radiological characteristics of the 28 patients were presented.

Results

A total of five types of hereditary neurological disorders were identified in 28 patients, including HSP (15/28), leukodystrophy (5/28), hereditary ataxia (2/28), methylmalonic acidemia/methylenetetrahydrofolate reductase deficiency (5/28), and Charcot-Marie-tooth atrophy (1/28). Patients in the HSP group had chronic courses, most of whom were lower limbs spasticity, mainly with axonal neuropathy, and thinning corpus callosum, white matter lesions and cerebellar atrophy in brain MRI. In the non-HSP groups, upper and lower limbs both involvement was more common. Patients with homocysteine remethylation disorders or Krabbe’s disease or autosomal recessive spastic ataxia of Charlevoix-Saguenay had diagnostic results in laboratory or imaging examination. A total of 12 new variants were obtained.

Conclusions

HSP had widespread clinical and genetic heterogeneity, and leukodystrophy, hereditary ataxia, Charcot-Marie-Tooth atrophy and homocysteine remethylation disorders accounted for a significant proportion of the proposed HSP. These diseases had different characteristics in clinical, laboratorial, electrophysiological, and radiological aspects, which could help differential diagnosis. Genetic analysis could ultimately provide a clear diagnosis, and broadening the scope of genetic testing could improve the positive rate of diagnosis.
Risk factors for pneumonitis in advanced extrapulmonary cancer patients treated with immune checkpoint inhibitors
Authors: Uchida Yasuki , Kinose Daisuke , Nagatani Yukihiro , Tanaka-Mizuno Sachiko , Nakagawa Hiroaki , Fukunaga Kentaro , Yamaguchi Masafumi , Nakano Yasutaka
Published: May 2022

Background

Immune-mediated pneumonitis has a high mortality rate; however, information regarding the related risk factors remains limited. This study aimed to analyze risk factors for pneumonitis, including smoking and lung metastasis (LM), in patients with extrapulmonary primary tumors.

Methods

Data of 110 patients treated with immune checkpoint inhibitors (ICIs) (nivolumab/pembrolizumab) for treating extrapulmonary primary tumors at the Shiga University of Medical Science Hospital between January 2015 and December 2019 were retrospectively collected. The association between the onset of pneumonitis and treatment-related factors was analyzed by logistic regression. The severity of pneumonitis was graded according to the Common Terminology Criteria for Adverse Events version 5.0. Risk factors, such as the absence or presence of interstitial lung disease (ILD) and LM, or other clinical factors, including smoking status before ICI administration, were analyzed.

Results

Multivariate analyses indicated that the amount of smoking was significantly associated with an increase in the development of all-grade pneumonitis types (odds ratio (OR) = 20.33, 95% confidence interval (CI) = 20.03–20.66; p = 0.029). LM and ILD were significantly related to an increase in the development of symptomatic pneumonitis (≥ Grade 2) (OR = 10.08, 95% CI = 1.69–199.81; p = 0.076, and OR = 6.76, 95% CI = 1.13–40.63; p = 0.037, respectively).

Conclusions

Pre-screening for ILD and LM and recognizing patients’ smoking history is important for determining the risk of ICI-induced pneumonitis and allowing safe ICI administration.
Regression to the mean in latent change score models: an example involving breastfeeding and intelligence
Authors: Sorjonen Kimmo , Nilsonne Gustav , Ingre Michael , Melin Bo
Published: May 2022

Background

Latent change score models are often used to study change over time in observational data. However, latent change score models may be susceptible to regression to the mean. Earlier observational studies have identified a positive association between breastfeeding and child intelligence, even when adjusting for maternal intelligence.

Method

In the present study, we investigate regression to the mean in the case of breastfeeding and intelligence of children. We used latent change score modeling to analyze intergenerational change in intelligence, both from mothers to children and backward from children to mothers, in the 1979 National Longitudinal Survey of Youth (NLSY79) dataset (N = 6283).

Results

When analyzing change from mothers to children, breastfeeding was found to have a positive association with intergenerational change in intelligence, whereas when analyzing backward change from children to mothers, a negative association was found.

Conclusions

These discrepant findings highlight a hidden flexibility in the analytical space and call into question the reliability of earlier studies of breastfeeding and intelligence using observational data.
Inclusive health: modeling COVID-19 in correctional facilities and communities
Authors: Greenhalgh Scott , Provencher Ashley
Published: May 2022

Background

Mass incarceration, commonly associated with overcrowding and inadequate health resources for incarcerated people, creates a fertile environment for the spread of the coronavirus disease 2019 (COVID-19) in U.S. correctional facilities. The exact role that correctional facilities play in enhancing COVID-19 spread and enabling community re-emergence of COVID-19 is unknown.

Methods

We constructed a novel stochastic model of COVID-19 transmission to estimate the impact of correctional facilities, specifically jails and state prisons, for enhancing disease transmission and enabling disease re-emergence in local communities. Using our model, we evaluated scenarios of testing and quarantining infected incarcerated people at 0.0, 0.5, and 1.0 times the rate that occurs for infected people in the community for population sizes of 5, 10, and 20 thousand people.

Results

Our results illustrate testing and quarantining an incarcerated population of 800 would reduce the probability of a major outbreak in the local community. In addition, testing and quarantining an incarcerated population would prevent between 10 to 2640 incidences of COVID-19 per year, and annually save up to 2010 disability-adjusted life years, depending on community size.

Conclusions

Managing COVID-19 in correctional facilities is essential to mitigate risks to community health, and thereby stresses the importance of improving the health standards of incarcerated people.
Dietary patterns, breakfast consumption, meals with family and associations with common mental disorders in adolescents: a school-based cross-sectional study
Authors: Gratão Lucia Helena Almeida , Pessoa Milene Cristine , Rodrigues da Silva Thales Philipe , Rocha Luana Lara , Louise Cassimiro Inácio Monique , Resende Prado Rangel de Oliveira Tatiana , de Freitas Cunha Cristiane , Mendes Larissa Loures
Published: May 2022

Background

Adolescence is a period of transition and vulnerabilities, in which mental illnesses can develop more easily. The objective of this work is to analyze the association of dietary patterns, breakfast consumption, and the practice of having meals accompanied by the family with the presence of Common Mental Disorders in Brazilian adolescents.

Methods

This is a cross-sectional study which analyzed data from 71,553 Brazilian adolescents aged 12–17 years, from the Study of Cardiovascular Risk in Adolescents (Portuguese acronym, “ERICA”). Principal Component Analysis was performed to identify dietary patterns, and Logistic Regression Models were performed to identify the associations between Common Mental Disorders, dietary patterns, and eating practices that are breakfast consumption and practice of having meals accompanied by family.

Results

Two patterns were found, a Healthy Dietary Pattern and an Unhealthy Dietary Pattern. Adolescents classified in the second (OR: 0.79; 95% CI 0.70—0.89) or third (OR: 0.86; 95% CI 0.77—0.96) tercile of the Healthy Dietary Pattern had a lower chance of having Common Mental Disorders. Eating breakfast sometimes (OR: 0.71; 95% CI 0.61—0.83) or almost every day/every day (OR: 0.54; 95% CI 0.47—0.62), and the practice of having the main meals with the family sometimes (OR: 0.69; 95% CI 0.57—0.84) or almost every day/every day (OR: 0.50; 95% CI 0.44–0.58), decreased the chance for Common Mental Disorders.

Conclusion

This study observed that healthy dietary patterns are associated with better mental health in adolescents, thus should be encouraged and promoted.
Sleep disturbance is associated with neck pain: a 3-year longitudinal study after the Great East Japan Earthquake
Authors: Yabe Yutaka , Hagiwara Yoshihiro , Sekiguchi Takuya , Sugawara Yumi , Tsuchiya Masahiro , Yoshida Shinichirou , Tsuji Ichiro
Published: May 2022

Background

Neck pain is a common health problem in the general population as well as in people after natural disasters. Sleep disturbances are gaining attention as risk factors for musculoskeletal pain; however, the association between sleep disturbance and neck pain has not been clarified. The present study aimed to clarify the association between sleep disturbance and neck pain, especially focusing on the effect of the duration of sleep disturbance, after the Great East Japan Earthquake.

Methods

This study used 3-year longitudinal data obtained from individuals (n = 2,059) living in disaster-affected areas after the Great East Japan Earthquake. Sleep disturbance and neck pain were investigated at 4, 5, 6, and 7 years after the disaster. Multivariate logistic regression analyses were used for the assessment.

Results

Sleep disturbance was significantly associated with neck pain, and the association was stronger as the duration of sleep disturbance increased (adjusted odds ratios [95% confidence intervals]: 1.84 [1.23–2.75] for “ < 1 year”; 2.41 [1.53–3.81] for “ ≥ 1 year and < 2 years”; 2.80 [2.09–3.76] for “ ≥ 2 years”). Furthermore, preceding sleep disturbance was significantly associated with the onset of neck pain, and the association was stronger as the duration of sleep disturbance increased (adjusted odds ratios [95% confidence intervals]: 1.86 [1.08–3.20] for “ < 1 year”; 2.39 [1.22–4.70] for “ ≥ 1 year and < 2 years”; 3.00 [1.94–4.65] for “ ≥ 2 years”).

Conclusions

Sleep disturbance is associated with neck pain, and long-lasting sleep disturbance strengthens the association. Clinicians should consider this association to effectively treat patients with neck pain, especially those affected by natural disasters.
Mitral valvuloplasty with left atrial appendage closure and pacemaker implantation in a dog with severe myxomatous mitral valve degeneration: a case report
Authors: Yoshida Tomohiko , Namiki Ryosuke , Matsuura Katsuhiro
Published: May 2022

Background

Mitral valvuloplasty (MVP) has been widely recognized as a treatment option for myxomatous mitral valve disease (MMVD). However, postoperative complications such as thromboembolism, arrhythmia, and pancreatitis in some cases have resulted in death. We treated a dog with severe MMVD complicated by impaired sinus function with MVP and pacemaker implantation. Also, due to an intrinsic procoagulant state and severe arrhythmia after the MVP, left atrial appendage (LAA) closure was performed to reduce the postoperative risk of thrombosis.

Case presentation

An 11-year-old castrated 7.5-kg male Miniature Schnauzer with a history of congestive heart failure was brought to Shiraishi Animal Hospital for MMVD surgical treatment. Echocardiography revealed an enlarged left atrium and ventricle secondary to MMVD. Sinus arrest with 2 to 3-second periods of asystole was identified by electrocardiogram. Mitral valvuloplasty was performed with cardiopulmonary bypass to treat the MMVD. After coronary reperfusion, there was no spontaneous electrical activity. Cardiac arrest continued. Based on this surgical outcome, a permanent pacemaker was implanted. In addition, LAA closure with an AtriClip was performed to prevent intra-atrial thrombus formation. Cardiac remodeling and congestion were ameliorated after surgery. Sinus rhythm was restored 5 days postoperatively; however, the patient continued pacemaker dependent. All cardiac drugs were discontinued 3 months after surgery. The owner reported no postoperative complications (i.e., thrombosis), and the patient was brought for a check-up 4 months after the operation in good health.

Conclusions

For surgical MMVD cases complicated with impaired sinus function, the chances of spontaneous sinus rhythm are low, requiring pacemaker implantation. LAA closure may be considered to protect against decreased atrial function after mitral valvuloplasty and prevent intra-atrial thrombus formation.
Identification of a novel CNV at the EYA4 gene in a Chinese family with autosomal dominant nonsyndromic hearing loss
Authors: Zhang Weixun , Song Jing , Tong Busheng , Ma Mengye , Guo Luo , Yuan Yasheng , Yang Juanmei
Published: May 2022

Background

Hereditary hearing loss is a heterogeneous class of disorders that exhibits various patterns of inheritance and involves many genes. Variants in theEYA4gene in DFNA10 are known to lead to postlingual, progressive, autosomal dominant nonsyndromic hereditary hearing loss.

Patients and methods

We collected a four-generation Chinese family with autosomal-dominant nonsyndromic hearing loss (ADNSHL). We applied targeted next-generation sequencing (TNGS) in three patients of this pedigree and whole-genome sequencing (WGS) in the proband. The intrafamilial cosegregation of the variant and the deafness phenotype were confirmed by PCR, gap-PCR and Sanger sequencing.

Results

A novel CNV deletion at 6q23 in exons 8–11 of theEYA4gene with a 10 bp insertion was identified by TNGS and WGS and segregated with the ADNSHL phenotypes.

Conclusions

Our results expanded the variant spectrum and genotype‒phenotype correlation of theEYA4gene and autosomal dominant nonsyndromic hereditary hearing loss in Chinese Han individuals. WGS is an accurate and effective method for verifying the genomic features of CNVs.
Bi-alignments with affine gaps costs
Authors: Stadler Peter F. , Will Sebastian
Published: May 2022

Background

Commonly, sequence and structure elements are assumed to evolve congruently, such that homologous sequence positions correspond to homologous structural features. Assuming congruent evolution, alignments based on sequence and structure similarity can therefore optimize both similarities at the same time in a single alignment. To model incongruent evolution, where sequence and structural features diverge positionally, we recently introduced bi-alignments. This generalization of sequence and structure-based alignments is best understood as alignments of two distinct pairwise alignments of the same entities: one modeling sequence similarity, the other structural similarity.

Results

Optimal bi-alignments with affine gap costs (or affine shift cost) for two constituent alignments can be computed exactly in quartic space and time. Even bi-alignments with affine shift and gap cost, as well as bi-alignment with sub-additive gap cost are optimized efficiently. Affine gap-cost bi-alignment of large proteins ($$\sim 930$$

∼
930

aa) can be computed.

Conclusion

Affine cost bi-alignments are of practical interest to study shifts of protein sequences and protein structures relative to each other.

Availability

The affine cost bi-alignment algorithm has been implemented in Python 3 and Cython. It is available as free software from https://github.com/s-will/BiAlign/releases/tag/v0.3 and as bioconda package .
Public knowledge and attitudes toward automated external defibrillators use among first aid eLearning course participants: a survey
Authors: Wang Yun-Ming , Lin Li-Ting , Jiang Jing-Hao , Jiang Yi , Jin Xiao-Qing
Published: May 2022

Objective

Survival from out-of-hospital cardiac arrest (OHCA) often depends on the effective and immediate use of automated external defibrillators (AEDs). Given that there have been few studies about AED use in China, the purpose of this study is to investigate the knowledge and attitudes regarding AED use among the Chinese public, then provide an effective suggestion for AED education strategies and legislation.

Method

The online survey was conducted among Chinese participants of the First Aid eLearning courses in June 2020.

Result

A total of 2565 (95.00%) surveys were completed, only 23.46% of respondents with non-medical related respondents reported having attended previous AED training courses. Regarding the basic knowledge of AEDs, few respondents (12.28%, n = 315) could answer all four questions correctly. 95.67% (n = 2454) were willing to learn AED use. Even if without the precondition of being skilled in AEDs, the female was more likely to rescue OHCA patients than the male (p = 0.003). Almost all respondents (96.65%) showed a strong willingness to rescue OHCA patients with training in using AEDs. The top four barriers to rescuing OHCA patients were lack of practical performing ability (60.47%), fear of hurting patients (59.30%), inadequate knowledge of resuscitation techniques (44.19%), and worry about taking legal responsibility (26.74%).

Conclusion

Our study reflects a deficiency of AED knowledge among the general public in China. However, positive attitudes towards rescuing OHCA patients and learning AED use were observed, which indicates that measures need to be taken to disseminate knowledge and use of AEDs.
Intravenous administration of a branched-chain amino-acid-free solution in children and adults with acute decompensation of maple syrup urine disease: a prospective multicentre observational study
Authors: Alili Jean-Meidi , Berleur Marie-Pierre , Husson Marie-Caroline , Mention Karine , Schiff Manuel , Arnoux Jean-Baptiste , Brassier Anaïs , Guemman Anne-Sophie , Grisel Coraline , Dubois Sandrine , Abi-Wardé Marie-Thérèse , Broissand Christine , Servais Aude , Dao Myriam , de Lonlay Pascale
Published: May 2022

Background

Patients with maple syrup urine disease (MSUD) experiencing metabolic decompensations have traditionally been treated with branched-chain amino acid (BCAA)-free mixture via oral or nasogastric administration routes. In some patients, enteral administration is not possible, either because the patient presents with vomiting, coma, or refuses nasogastric administration, thus intravenous (IV) BCAA-free solution is an appropriate intervention for these challenging cases.

Aims

This study aimed to evaluate the effectiveness and safety of managing metabolic decompensations by administering an IV BCAA-free solution.

Methods

This is an observational prospective study of data from MSUD patients hospitalised for decompensation episodes between 2010 and 2016 at 6 centres for rare metabolic diseases in France.

Results

A total of 24 patients (16 males; 8 females) experiencing 126 MSUD metabolic decompensation episodes (39 in children; 87 in adults) were admitted to hospital. At presentation, mean leucine plasma concentration was ≥ 381 µmol/L in 113/126 (89.7%) episodes. Children were treated with continuous IV BCAA-free solution at doses of 0.8 to 2.0 g/kg/day, for 4.8 days and adults for 3.8 days at doses of 0.5 to 2.6 g/kg/day. In the efficacy set of 102 analysable episodes leucine concentrations were normalised (to below 381 µmol/L) in 82% (n = 18/22) of episodes in children and in 84% (n = 67/80) of episodes in adults. Mean time to leucine normalisation was 3.0 days. This was significantly (p < 0.001) shorter than the algorithmically predicted time to leucine normalisation with traditional BCAA-free mixture. Duration of hospitalisation was significantly longer for children than for adults (7.1 days in children vs 5.2 days in adults, p = 0.012). No treatment-related adverse events were reported in any patients on IV BCAA-free solution.

Conclusion

The IV BCAA-free solution is safe and effective in normalising leucine concentrations during MSUD decompensation episodes in both children and adults, offering a practical treatment alternative for those patients who cannot receive BCAA-free mixture via oral or nasogastric routes.
Tissue engineering in age-related macular degeneration: a mini-review
Authors: Wu Andres , Lu Renhao , Lee Esak
Published: May 2022

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the macula, leading to severe visual loss in the elderly population. There are two types of AMD: non-exudative (‘dry’) AMD and exudative (‘wet’) AMD. Non-exudative AMD is characterized by drusen formation and macular atrophy, while the blood vessels are not leaky. Exudative AMD is a more advanced form of the disease, featured with abnormal blood vessel growth and vascular leakage. Even though anti-angiogenic therapies have been effective in treating wet AMD by normalizing blood vessels, there is no treatment available to prevent or treat dry AMD. Currently, the mechanisms of drusen formation and macular atrophy in the dry AMD are poorly understood, in part because the currently available in vivo models of AMD could not decouple and isolate the complex biological and biophysical factors in the macular region for a detailed mechanism study, including the complement system, angiogenesis factors, extracellular matrix, etc. In the present review article, we describe the biological background of AMD and the key cells and structures in AMD, including retinal epithelium, photoreceptor, Bruch’s membrane, and choriocapillaris. We also discuss pre-clinical animal models of AMD and in vivo tissue-engineered approaches, including cell suspension injection and organoid-derived cell sheet transplantation. We also discuss in vitro tissue-engineered models for AMD research. Specifically, we evaluate and compare currently available two- and three-dimensional AMD tissue-engineered models that mimic key anatomical players in AMD progression, including pathophysiological characteristics in Bruch’s membrane, photoreceptor, and choriocapillaris. Finally, we discuss the limitation of current AMD models and future directions.
Adolescent perspectives on participating in a feasibility trial investigating shoe inserts for patellofemoral pain
Authors: O'Sullivan Isobel C. , da Costa Nathalia Cordeiro , Franettovich Smith Melinda M. , Vicenzino Bill , Crossley Kay M. , Kamper Steven J. , van Middelkoop Marienke , Menz Hylton B. , Tucker Kylie , O'Leary Karina T. , Collins Natalie J.
Published: May 2022

Background

Patellofemoral pain (PFP) affects one‐quarter of adolescents, yet there are few evidence‐informed recommendations to treat PFP in this population. HAPPi Kneecaps! is a randomised, controlled, participant‐ and assessor‐blind, parallel‐group feasibility trial of shoe inserts for adolescents with PFP. The aim of this qualitative study was to explore adolescents' perspectives of participating in HAPPi Kneecaps!.

Methods

All 36 adolescents with PFP from the HAPPi Kneecaps! study were invited to participate in semi‐structured interviews. We used a descriptive qualitative methodology underpinned by a relativist framework to investigate adolescents' perspectives on participating in the trial. Inductive thematic analysis was used to examine patterns regarding how each adolescent experienced the HAPPi Kneecaps! study within their social, cultural, and historical contexts.

Results

14 out of 36 HAPPi Kneecaps! participants provided consent and participated in interviews (12 females; mean [SD] age 14.9 [2.4] years). Overall, most adolescents responded positively when discussing their experience, such as improvements in their knee pain and satisfaction with how the study was run. Major themes that were generated from the analysis and feedback were: (1) shoe inserts require little effort to use; (2) perceptions of the program were generally positive; (3) participation in the trial could be made easier; (4) warm weather matters; and (5) life happens.

Conclusion

Adolescents with PFP who participated in the HAPPi Kneecaps! study found that shoe inserts were easy to wear. Most adolescents experienced an improvement in their symptoms and enhanced participation in sport and exercise. Adolescents with PFP prefer an option for warmer climates (e.g. flip flops or sandals), access to online logbooks, and clinicians who are easily accessible.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000957190. Date registered: 8/07/2019.
Trials using deferred consent in the emergency setting: a systematic review and narrative synthesis of stakeholders’ attitudes
Authors: Fitzpatrick Aran , Wood Fiona , Shepherd Victoria
Published: May 2022

Background

Patients with acute conditions often lack the capacity to provide informed consent, and narrow therapeutic windows mean there is no time to seek consent from surrogates prior to treatment being commenced. One method to enable the inclusion of this study population in emergency research is through recruitment without prior consent, often known as ‘deferred consent’. However, empirical studies have shown a large disparity in stakeholders’ opinions regarding this enrolment method. This systematic review aimed to understand different stakeholder groups’ attitudes to deferred consent, particularly in relation to the context in which deferred consent might occur.

Methods

Databases including MEDLINE, EMCare, PsychINFO, Scopus, and HMIC were searched from 1996 to January 2021. Eligible studies focussed on deferred consent processes for adults only, in the English language, and reported empirical primary research. Studies of all designs were included. Relevant data were extracted and thematically coded using a narrative approach to ‘tell a story’ of the findings.

Results

Twenty-seven studies were included in the narrative synthesis. The majority examined patient views (n = 19). Data from the members of the public (n = 5) and health care professionals (n =5) were also reported. Four overarching themes were identified: level of acceptability of deferred consent, research-related factors influencing acceptability, personal characteristics influencing views on deferred consent, and data use after refusal of consent or participant death.

Conclusions

This review indicates that the use of deferred consent would be most acceptable to stakeholders during low-risk emergency research with a narrow therapeutic window and where there is potential for patients to benefit from their inclusion. While the use of narrative synthesis allowed assessment of the included studies, heterogeneous outcome measures meant that variations in study results could not be reliably attributed to the different trial characteristics. Future research should aim to develop guidance for research ethics committees when reviewing trials using deferred consent in emergency research and investigate more fully the views of healthcare professionals which to date have been explored less than patients and members of the public.

Trial registration

PROSPERO CRD42020223623
Hope and meaning-making in phase 1 oncology trials: a systematic review and thematic synthesis of qualitative evidence on patient-participant experiences
Authors: Escritt Kate , Mann Mala , Nelson Annmarie , Harrop Emily
Published: May 2022

Background

Phase 1 drug trials are popular treatment options for patients with advanced disease, despite the greater levels of uncertainty associated with them. However, their meaning and consequences for patient-participants remains under-explored. This review synthesises the qualitative evidence of patients’ experiences of participating in phase 1 oncology trials, exploring their decisions to take part and the impacts of these trials on patient wellbeing.

Methods

A comprehensive literature search involving medical subject headings (MeSH) and keywords was undertaken in the following databases: MEDLINE, EMBASE, PsycINFO, Scopus, CINAHL, and Cochrane CENTRAL, with supplementary searches also conducted. Studies were independently screened for inclusion by two researchers. Included studies were critically appraised and data extracted using standardised forms. Qualitative results were analysed using thematic synthesis.

Results

Three main themes were identified across 13 studies: decision-making and joining the trial; experiences of taking part in the trial and hope and coping. Patients primarily joined trials hoping for therapeutic benefits, sentiments which prevailed and shaped their experiences across their trial journey. Rather than indicate therapeutic misconception based on poor understanding, patient perspectives more commonly pointed to differences between hope and expectation and cultural narratives of staying positive, trying everything and trusting in experts.

Conclusions

These findings challenge information-based models of consent, favouring coping frameworks which account for the role of hope and meaning-making during serious illness. Personalised consideration of existential and quality-of-life matters before and during trials is recommended, including palliative and supportive care alternatives to active treatment.

Review Registration

The review was registered with PROSPERO international prospective register of systematic reviews (CRD 42020163250).
Reduced anticoagulation targets in extracorporeal life support (RATE): study protocol for a randomized controlled trial
Authors: van Minnen Olivier , Oude Lansink-Hartgring Annemieke , van den Boogaard Bas , van den Brule Judith , Bulpa Pierre , Bunge Jeroen J. H. , Delnoij Thijs S. R. , Elzo Kraemer Carlos V. , Kuijpers Marijn , Lambermont Bernard , Maas Jacinta J. , de Metz Jesse , Michaux Isabelle , van de Pol Ineke , van de Poll Marcel , Raasveld S. Jorinde , Raes Matthias , dos Reis Miranda Dinis , Scholten Erik , Simonet Olivier , Taccone Fabio S. , Vallot Frederic , Vlaar Alexander P. J. , van den Bergh Walter M.
Published: May 2022

Background

Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT).

However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome.

Methods

We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2–2.5 times baseline aPTT, 1.5–2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months.

Discussion

We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO.

Trial registration

ClinicalTrials.gov NCT04536272. Registered on 2 September 2020. Netherlands Trial Register NL7969