bluuebunny/crossref_metadata_2025 huggingface dataset:
Global point-of-care ultrasound education and training in the age of COVID-19
Authors: Eke Onyinyechi F. , Henwood Patricia C. , Wanjiku Grace W. , Fasina Abiola , Kharasch Sigmund J. , Shokoohi Hamid
Published: February 2021

The COVID-19 pandemic has disrupted traditional global point-of-care ultrasound (POCUS) education and training, as a result of travel restrictions. It has also provided an opportunity for innovation using a virtual platform. Tele-ultrasound and video-conferencing are alternative and supportive tools to augment global POCUS education and training. There is a need to support learners and experts to ensure that maximum benefit is gained from the use of these innovative modalities.
FiNGS: high quality somatic mutations using filters for next generation sequencing
Authors: Wardell Christopher Paul , Ashby Cody , Bauer Michael Anton
Published: February 2021

Background

Somatic variant callers are used to find mutations in sequencing data from cancer samples. They are very sensitive and have high recall, but also may produce low precision data with a large proportion of false positives. Further ad hoc filtering is commonly performed after variant calling and before further analysis. Improving the filtering of somatic variants in a reproducible way represents an unmet need. We have developed Filters for Next Generation Sequencing (FiNGS), software written specifically to address these filtering issues.

Results

Developed and tested using publicly available sequencing data sets, we demonstrate that FiNGS reliably improves upon the precision of default variant caller outputs and performs better than other tools designed for the same task.

Conclusions

FiNGS provides researchers with a tool to reproducibly filter somatic variants that is simple to both deploy and use, with filters and thresholds that are fully configurable by the user. It ingests and emits standard variant call format (VCF) files and will slot into existing sequencing pipelines. It allows users to develop and implement their own filtering strategies and simple sharing of these with others.
MeltingPlot, a user-friendly online tool for epidemiological investigation using High Resolution Melting data
Authors: Perini Matteo , Batisti Biffignandi Gherard , Di Carlo Domenico , Pasala Ajay Ratan , Piazza Aurora , Panelli Simona , Zuccotti Gian Vincenzo , Comandatore Francesco
Published: February 2021

Background

The rapid identification of pathogen clones is pivotal for effective epidemiological control strategies in hospital settings. High Resolution Melting (HRM) is a molecular biology technique suitable for fast and inexpensive pathogen typing protocols. Unfortunately, the mathematical/informatics skills required to analyse HRM data for pathogen typing likely limit the application of this promising technique in hospital settings.

Results

MeltingPlot is the first tool specifically designed for epidemiological investigations using HRM data, easing the application of HRM typing to large real-time surveillance and rapid outbreak reconstructions. MeltingPlot implements a graph-based algorithm designed to discriminate pathogen clones on the basis of HRM data, producing portable typing results. The tool also merges typing information with isolates and patients metadata to create graphical and tabular outputs useful in epidemiological investigations and it runs in a few seconds even with hundreds of isolates. Availability: https://skynet.unimi.it/index.php/tools/meltingplot/.

Conclusions

The analysis and result interpretation of HRM typing protocols can be not trivial and this likely limited its application in hospital settings. MeltingPlot is a web tool designed to help the user to reconstruct epidemiological events by combining HRM-based clustering methods and the isolate/patient metadata. The tool can be used for the implementation of HRM based real time large scale surveillance programs in hospital settings.
A simple method to estimate the in-house limit of detection for genetic mutations with low allele frequencies in whole-exome sequencing analysis by next-generation sequencing
Authors: Miura Takumi , Yasuda Satoshi , Sato Yoji
Published: February 2021

Background

Next-generation sequencing (NGS) has profoundly changed the approach to genetic/genomic research. Particularly, the clinical utility of NGS in detecting mutations associated with disease risk has contributed to the development of effective therapeutic strategies. Recently, comprehensive analysis of somatic genetic mutations by NGS has also been used as a new approach for controlling the quality of cell substrates for manufacturing biopharmaceuticals. However, the quality evaluation of cell substrates by NGS largely depends on the limit of detection (LOD) for rare somatic mutations. The purpose of this study was to develop a simple method for evaluating the ability of whole-exome sequencing (WES) by NGS to detect mutations with low allele frequency. To estimate the LOD of WES for low-frequency somatic mutations, we repeatedly and independently performed WES of a reference genomic DNA using the same NGS platform and assay design. LOD was defined as the allele frequency with a relative standard deviation (RSD) value of 30% and was estimated by a moving average curve of the relation between RSD and allele frequency.

Results

Allele frequencies of 20 mutations in the reference material that had been pre-validated by droplet digital PCR (ddPCR) were obtained from 5, 15, 30, or 40 G base pair (Gbp) sequencing data per run. There was a significant association between the allele frequencies measured by WES and those pre-validated by ddPCR, whose p-value decreased as the sequencing data size increased. By this method, the LOD of allele frequency in WES with the sequencing data of 15 Gbp or more was estimated to be between 5 and 10%.

Conclusions

For properly interpreting the WES data of somatic genetic mutations, it is necessary to have a cutoff threshold of low allele frequencies. The in-house LOD estimated by the simple method shown in this study provides a rationale for setting the cutoff.
Genome-wide association studies detects candidate genes for wool traits by re-sequencing in Chinese fine-wool sheep
Authors: Zhao Hongchang , Guo Tingting , Lu Zengkui , Liu Jianbin , Zhu Shaohua , Qiao Guoyan , Han Mei , Yuan Chao , Wang Tianxiang , Li Fanwen , Zhang Yajun , Hou Fujun , Yue Yaojing , Yang Bohui
Published: February 2021

Background

The quality and yield of wool determine the economic value of the fine-wool sheep. Therefore, discovering markers or genes relevant to wool traits is the cornerstone for the breeding of fine-wool sheep. In this study, we used the Illumina HiSeq X Ten platform to re-sequence 460 sheep belonging to four different fine-wool sheep breeds, namely, Alpine Merino sheep (AMS), Chinese Merino sheep (CMS), Aohan fine-wool sheep (AHS) and Qinghai fine-wool sheep (QHS). Eight wool traits, including fiber diameter (FD), fiber diameter coefficient of variance (FDCV), fiber diameter standard deviation (FDSD), staple length (SL), greasy fleece weight (GFW), clean wool rate (CWR), staple strength (SS) and staple elongation (SE) were examined. A genome-wide association study (GWAS) was performed to detect the candidate genes for the eight wool traits.

Results

A total of 8.222 Tb of raw data was generated, with an average of approximately 8.59X sequencing depth. After quality control, 12,561,225 SNPs were available for analysis. And a total of 57 genome-wide significant SNPs and 30 candidate genes were detected for the desired wool traits. Among them, 7 SNPs and 6 genes are related to wool fineness indicators (FD, FDCV and FDSD), 10 SNPs and 7 genes are related to staple length, 13 SNPs and 7 genes are related to wool production indicators (GFW and CWR), 27 SNPs and 10 genes associated with staple elongation. Among these candidate genes, UBE2E3 and RHPN2 associated with fiber diameter, were found to play an important role in keratinocyte differentiation and cell proliferation. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results, revealed that multitude significant pathways are related to keratin and cell proliferation and differentiation, such as positive regulation of canonical Wnt signaling pathway (GO:0090263).

Conclusion

This is the first GWAS on the wool traits by using re-sequencing data in Chinese fine-wool sheep. The newly detected significant SNPs in this study can be used in genome-selective breeding for the fine-wool sheep. And the new candidate genes would provide a good theoretical basis for the fine-wool sheep breeding.
The seroprevalence and kinetics of IgM and IgG in the progression of COVID-19
Authors: Qin Xuzhen , Shen Jun , Dai Erhei , Li Haolong , Tang Guodong , Zhang Lixia , Hou Xin , Lu Minya , Wu Xian , Duan Simeng , Zhang Jingjia , Tsoi Man-Fung , Jiang Ping , Li Yongzhe
Published: February 2021

Background

SARS-CoV-2 is a novel coronavirus first recognized in late December 2019 that causes coronavirus disease 19 (COVID-19). Due to the highly contagious nature of SARS-CoV-2, it has developed into a global pandemic in just a few months. Antibody testing is an effective method to supplement the diagnosis of COVID-19. However, multicentre studies are lacking to support the understanding of the seroprevalence and kinetics of SARS-CoV-2 antibodies in COVID-19 epidemic regions.

Method

A multicentre cross-sectional study of suspected and confirmed patients from 4 epidemic cities in China and a cohort study of consecutive follow-up patients were conducted from 29/01/2020 to 12/03/2020. IgM and IgG antibodies elicited by SARS-CoV-2 were tested by a chemiluminescence assay. Clinical information, including basic demographic data, clinical classification, and time interval from onset to sampling, was collected from each centre.

Results

A total of 571 patients were enrolled in the cross-sectional study, including 235 COVID-19 patients and 336 suspected patients, each with 91.9%:2.1% seroprevalence of SARS-CoV-2 IgG and 92.3%:5.4% seroprevalence of SARS-CoV-2 IgM. The seroprevalence of SARS-CoV-2 IgM and IgG in COVID-19 patients was over 70% less than 7 days after symptom onset. Thirty COVID-19 patients were enrolled in the cohort study and followed up for 20 days. The peak concentrations of IgM and IgG were reached on the 10th and 20th days, respectively, after symptom onset. The seroprevalence of COVID-19 IgG and IgM increased along with the clinical classification and treatment time delay.

Conclusion

We demonstrated the kinetics of IgM and IgG SARS-CoV-2 antibodies in COVID-19 patients and the association between clinical classification and antibodies, which will contribute to the interpretation of IgM and IgG SARS-CoV-2 antibody tests and in predicting the outcomes of patients with COVID-19.
Amplicon-based skin microbiome profiles collected by tape stripping with different adhesive film dressings: a comparative study
Authors: Ogai Kazuhiro , Shibata Kana , Takahashi Natsuki , Ogura Kohei , Okamoto Shigefumi , Sugama Junko
Published: February 2021

Background

Medical film dressings have been used to obtain skin microbiota for skin microbiome studies, although their adhesive force may be so strong that the skin could be injured when applied to those who have fragile skin, such as older people. Several products with less adhesive force are available, although their applicability for skin microbiome studies remains unknown. This study aimed to test whether the dressings with less adhesive force could be used for amplicon-based skin microbiome studies. A set of three different film dressings, with acrylic, urethane, or silicone adhesive, was applied to the back skin of nine healthy young participants. The copy number of the 16S ribosomal RNA (rRNA) gene, microbial compositions, and alpha and beta diversity indices were analyzed by amplicon analysis of the 16S rRNA gene using next-generation sequencing and were compared among the three film dressings.

Results

The dressing with acrylic adhesive yielded the highest copy number of 16S rRNA genes, followed by that with urethane adhesive. The silicone-adhesive dressing yielded a significantly lower copy number of the 16S rRNA gene. The microbial composition of skin microbiota was similar among the three film dressings, although significant differences in the relative abundance of Pseudomonas species and alpha diversity indices were found in the silicone-adhesive dressing. The Bray–Curtis dissimilarity was significantly higher between the acrylic- and silicone-adhesive dressings than between the acrylic- and urethane-adhesive dressings. No adverse effects related to tape stripping were observed for any of the film dressings.

Conclusion

We recommend dressings with acrylic or urethane adhesive for amplicon-based skin microbiome studies. An acrylic adhesive has an advantage in the yield of skin microbiota, and a urethane adhesive should be chosen when applied to fragile skin. The adhesive force of the dressing with silicone adhesive was too weak to be used for collecting skin microbiota.
Functional gene assessment of bread wheat: breeding implications in Ningxia Province
Authors: Zhang Weijun , Zhao Junjie , He Jinshang , Kang Ling , Wang Xiaoliang , Zhang Fuguo , Hao Chenyang , Ma Xiongfeng , Chen Dongsheng
Published: February 2021

Background

The overall genetic distribution and divergence of cloned genes among bread wheat varieties that have occurred during the breeding process over the past few decades in Ningxia Province, China, are poorly understood. Here, we report the genetic diversities of 44 important genes related to grain yield, quality, adaptation and resistance in 121 Ningxia and 86 introduced wheat cultivars and advanced lines.

Results

The population structure indicated characteristics of genetic components of Ningxia wheat, including landraces of particular genetic resources, introduced varieties with rich genetic diversities and modern cultivars in different periods. Analysis of allele frequencies showed that the dwarfing alleles Rht-B1b at Rht-B1 and Rht-D1b at Rht-D1, 1BL/1RS translocation, Hap-1 at GW2-6B and Hap-H at Sus2-2B are very frequently present in modern Ningxia cultivars and in introduced varieties from other regions but absent in landraces. This indicates that the introduced wheat germplasm with numerous beneficial genes is vital for broadening the genetic diversity of Ningxia wheat varieties. Large population differentiation between modern cultivars and landraces has occurred in adaptation genes. Founder parents carry excellent allele combinations of important genes, with a higher number of favorable alleles than modern cultivars. Gene flow analysis showed that six founder parents have greatly contributed to breeding improvement in Ningxia Province, particularly Zhou 8425B, for yield-related genes.

Conclusions

Varieties introduced from other regions with rich genetic diversity and landraces with well-adapted genetic resources have been applied to improve modern cultivars. Founder parents, particularly Zhou 8425B, for yield-related genes have contributed greatly to wheat breeding improvement in Ningxia Province. These findings will greatly benefit bread wheat breeding in Ningxia Province as well as other areas with similar ecological environments.
High-sensitive cardiac troponin for the diagnosis of acute myocardial infarction in different chronic kidney disease stages
Authors: Ren Daijin , Huang Tianlun , Liu Xin , Xu Gaosi
Published: February 2021

Background

Chronic kidney disease (CKD) are associated with acute myocardial infarction (AMI). High-sensitive cardiac troponin (hs-cTn) has been evidenced to enhance the early diagnostic accuracy of AMI, but hs-cTn levels are often chronically elevated in CKD patients, which reduces their diagnostic utility. The aim of this study was to derive optimal cutoff-values of hs-cTn levels in patients with CKD and suspected AMI.

Methods

In this retrospective paper, a total of 3295 patients with chest pain (2758 in AMI group and 537 in Non-AMI group) were recruited, of whom 23.1% were had an estimated glomerular filtration rate (eGFR) of < 60 mL min−1 (1.73 m2)−1. Hs-cTnI values were measured at presentation.

Results

AMI was diagnosed in 83.7% of all patients. The optimal value of hs-TnI in diagnosing AMI was 1.15 ng mL−1, which were higher in males than females comparing different cutoff-values of subgroups divided by age, gender and renal function, and which increased monotonically with decreasing of eGFR because in patients with CKD without AMI, the correlation between hs-cTnI and renal function is low but significant (r2 = 0.067, P < 0.001).

Conclusions

Different optimal cutoff-values of hs-cTnI in the diagnosis of AMI in patients with CKD were helpful to the clinical diagnosis of AMI in various populations and were higher in males than females, but which was needed to be validated by multicenter randomized controlled clinical studies in the future.
Natural history observations in moderate aortic stenosis
Authors: Du Yu , Gössl Mario , Garcia Santiago , Enriquez-Sarano Maurice , Cavalcante Joao L. , Bae Richard , Hashimoto Go , Fukui Miho , Lopes Bernardo , Ahmed Aisha , Schmidt Christian , Stanberry Larissa , Garberich Ross , Bradley Steven M. , Steffen Robert , Sorajja Paul
Published: February 2021

Background

The natural history of patients with moderate aortic stenosis (AS) is poorly understood. We aimed to determine the long-term outcomes of patients with moderate AS.

Methods

We examined patients with moderate AS defined by echocardiography in our healthcare system, and performed survival analyses for occurrence of death, heart failure (HF) hospitalization, and progression of AS, with accounting for symptoms, left ventricular dysfunction, and comorbidities.

Results

We examined 729 patients with moderate AS (median age, 76 years; 59.9 % men) with a median follow-up of 5.0 years (interquartile range: 2.0 to 8.1 years). The 5-year overall survival was 52.3 % (95 % confidence interval [CI]: 48.6 % to 56.0 %) and survival free of death or HF hospitalization was 43.2 % (95 % CI: 39.5 % to 46.9 %). Worse New York Heart Association (NYHA) functional class was associated with poor long-term survival, with mortality rates ranging from 7.9 % (95 % CI: 6.6–9.2 %) to 25.2 % (95 % CI: 20.2–30.3 %) per year. Among patients with minimal or no symptoms, no futility markers, and preserved left ventricular function, 5-year overall survival was 71.9 % (95 % CI: 66.4–77.4 %) and survival free of death or HF hospitalization was 61.4 % (95 % CI: 55.5–67.3 %). Risk factors associated with adverse events were age, NYHA class, low ejection fraction and high aortic valve velocity (allp < 0.05).

Conclusions

Patients with moderate AS are at significant risk of death. Our findings highlight the need for more study into appropriate therapeutic interventions to improve the prognosis of these patients.
Prevalence and associated factors of the career plateau of primary care providers in Heilongjiang, China: a cross-sectional study
Authors: Liu Di , Yang Xu , Li Qinglin , Shi Lei , Tang Qiaoran
Published: February 2021

Background

Primary care providers are pillars of China’s medical and health sectors. However, due to the gap between career expectations and reality, they enter a career plateau phase through excessive pressure. This study aims to examine the prevalence and associated factors of the career plateau of primary care providers in Heilongjiang Province, China, and proposes strategies to improve and promote their career advancement.

Methods

Based on city-level GDP growth in the province, a questionnaire survey was conducted among 1500 primary care providers (effective response rate = 85.8%). Pearson’s chi-square analysis and binary logistic regression were used to analyse the factors associated with their career plateau.

Results

The prevalence rate of career plateau was 61.8% among primary care provider respondents. The factors associated with a career plateau included having a spouse (OR = 1.394, 95%CI = 1.056–1.839), working more than 40 h per week (OR = 1.473, 95%CI = 1.146–1.893); working for 11–20 years (OR = 1.607, 95%CI = 1.150–2.246); working for more than 20 years (OR = 2.818, 95%CI = 1.938–4.097); having an average monthly income of 3001–4000 yuan (OR = 1.886, 95%CI = 1.197–2.969) or 4001–5000 yuan (OR = 2.104, 95%CI = 1.256–3.524); and reporting unsatisfactory or very unsatisfactory sleep quality (OR = 1.838, 95%CI = 1.317–2.567).

Conclusions

Primary care providers in Heilongjiang Province face a high career plateau, with marital status, weekly working hours, number of years employed, monthly average income, and sleep quality considered associated factors. To eliminate negative factors of the career plateau, it is necessary to provide support to primary care providers in four domains: individual, organisation, society, and policy.
Correlation between lung infection severity and clinical laboratory indicators in patients with COVID-19: a cross-sectional study based on machine learning
Authors: Wang Xingrui , Che Qinglin , Ji Xiaoxiao , Meng Xinyi , Zhang Lang , Jia Rongrong , Lyu Hairong , Bai Weixian , Tan Lingjie , Gao Yanjun
Published: February 2021

Background

Coronavirus disease 2019 (COVID-19) has caused a global pandemic that has raised worldwide concern. This study aims to investigate the correlation between the extent of lung infection and relevant clinical laboratory testing indicators in COVID-19 and to analyse its underlying mechanism.

Methods

Chest high-resolution computer tomography (CT) images and laboratory examination data of 31 patients with COVID-19 were extracted, and the lesion areas in CT images were quantitatively segmented and calculated using a deep learning (DL) system. A cross-sectional study method was carried out to explore the differences among the proportions of lung lobe infection and to correlate the percentage of infection (POI) of the whole lung in all patients with clinical laboratory examination values.

Results

No significant difference in the proportion of infection was noted among various lung lobes (P > 0.05). The POI of total lung was negatively correlated with the peripheral blood lymphocyte percentage (L%) (r = − 0.633, P < 0.001) and lymphocyte (LY) count (r = − 0.555, P = 0.001) but positively correlated with the neutrophil percentage (N%) (r = 0.565, P = 0.001). Otherwise, the POI was not significantly correlated with the peripheral blood white blood cell (WBC) count, monocyte percentage (M%) or haemoglobin (HGB) content. In some patients, as the infection progressed, the L% and LY count decreased progressively accompanied by a continuous increase in the N%.

Conclusions

Lung lesions in COVID-19 patients are significantly correlated with the peripheral blood lymphocyte and neutrophil levels, both of which could serve as prognostic indicators that provide warning implications, and contribute to clinical interventions in patients.
Refining MDR-TB treatment regimens for ultra short therapy (TB-TRUST): study protocol for a randomized controlled trial
Authors: Weng Taoping , Sun Feng , Li Yang , Chen Jiazhen , Chen Xinchang , Li Rong , Ge Shijia , Zhao Yanlin , Zhang Wenhong
Published: February 2021

Background

Multidrug-resistant tuberculosis (MDR-TB) are unsatisfied to treat, pressing more effective and innovative treatment regimens. New efficient regimens for MDR-TB have obtained high treatment success rates. However, those regimens without drug susceptibility testing (DST) are also likely to contribute to the emergence of resistance. Precision treatments guided by DST might optimize the patients’ treatment outcome individually and minimize resistance amplification.

Methods

TB-TRUST is a phase III, multicenter, open-label, randomized controlled clinical trial of non-inferiority comparing the treatment success rate between the World Health Organization (WHO) shorter regimen and the refined ultra-short regimen for fluoroquinolones and second-line injectable drugs susceptible rifampicin-resistant TB. The control arm uses the WHO injectable-containing shorter regimen for 36–44 weeks depending on time of sputum smear conversion. The investigational arm uses a refined ultra-short regimen guided by molecular DST to pyrazinamide via whole-genome sequencing (WGS) to optimize the treatment of pyrazinamide-susceptible patients with levofloxacin, linezolid, cycloserine and pyrazinamide for 24–32 weeks and pyrazinamide-resistant with levofloxacin, linezolid, cycloserine and clofazimine for 36–44 weeks. The primary outcome is the treatment success rate without relapse at 84 weeks after treatment initiation. Secondary outcomes include the time of sputum culture conversion and occurrence of adverse events. Assuming α = 0.025 level of significance (one-sided test), a power of 80%, a < 10% difference in treatment success rate between control arm and investigational (80% vs. 82%), and a 5% lost follow-up rate, the number of participants per arm to show non-inferiority was calculated as 177(354 in total).

Discussion

Rapid molecular testing distinguishes patients who are eligible for shorter regimen with fluoroquinolone and the WGS-guided results shorten the treatment to 6 months for pyrazinamide susceptible patients. It’s foreseeable that not only novel developed medicines, but also traditional powerful medicines with the susceptibility confirmed by DST are the key factors to ensure the effect of anti-MDR-TB drugs. As a DST-guided precision treatment, TB-TRUST are expected to optimize therapy outcome in more patients who cannot afford the expensive new medicines and minimize and even avoid resistance amplification with the rational use of anti-TB drugs.

Trail registration

ClinicalTrial.gov, NCT03867136. Registered on March 7, 2019.
Spatial clustering of livestock Anthrax events associated with agro-ecological zones in Kenya, 1957–2017
Authors: Nderitu Leonard M. , Gachohi John , Otieno Frederick , Mogoa Eddy G. , Muturi Mathew , Mwatondo Athman , Osoro Eric M. , Ngere Isaac , Munyua Peninah M. , Oyas Harry , Njagi Obadiah , Lofgren Eric , Marsh Thomas , Widdowson Marc-Alain , Bett Bernard , Njenga M. Kariuki
Published: February 2021

Background

Developing disease risk maps for priority endemic and episodic diseases is becoming increasingly important for more effective disease management, particularly in resource limited countries. For endemic and easily diagnosed diseases such as anthrax, using historical data to identify hotspots and start to define ecological risk factors of its occurrence is a plausible approach. Using 666 livestock anthrax events reported in Kenya over 60 years (1957–2017), we determined the temporal and spatial patterns of the disease as a step towards identifying and characterizing anthrax hotspots in the region.

Methods

Data were initially aggregated by administrative unit and later analyzed by agro-ecological zones (AEZ) to reveal anthrax spatio-temporal trends and patterns. Variations in the occurrence of anthrax events were estimated by fitting Poisson generalized linear mixed-effects models to the data with AEZs and calendar months as fixed effects and sub-counties as random effects.

Results

The country reported approximately 10 anthrax events annually, with the number increasing to as many as 50 annually by the year 2005. Spatial classification of the events in eight counties that reported the highest numbers revealed spatial clustering in certain administrative sub-counties, with 12% of the sub-counties responsible for over 30% of anthrax events, whereas 36% did not report any anthrax disease over the 60-year period. When segregated by AEZs, there was significantly greater risk of anthrax disease occurring in agro-alpine, high, and medium potential AEZs when compared to the agriculturally low potential arid and semi-arid AEZs of the country (p < 0.05). Interestingly, cattle were > 10 times more likely to be infected by B. anthracis than sheep, goats, or camels. There was lower risk of anthrax events in August (P = 0.034) and December (P = 0.061), months that follow long and short rain periods, respectively.

Conclusion

Taken together, these findings suggest existence of certain geographic, ecological, and demographic risk factors that promote B. anthracis persistence and trasmission in the disease hotspots.
Post‐traumatic cerebral fat embolism syndrome with a favourable outcome: a case report
Authors: Wang Wei , Chen Weibi , Zhang Yan , Su Yingying , Wang Yuping
Published: February 2021

Background

Fat embolism syndrome (FES) is a change in physiology resulting from mechanical causes, trauma, or sepsis. Neurological manifestations of FES can vary from mild cognitive changes to coma and even cerebral oedema and brain death. Here, we present an unusual case of cerebral fat emboli that occurred in the absence of acute chest syndrome or right-to-left shunt.

Case presentation

A previously healthy 57-year-old right-handed male was admitted to our department because of unconsciousness after a car accident for 3 days. He suffered from multiple fractures of the bilateral lower extremities and pelvis. This patient had severe anaemia and thrombocytopenia. Head MRI showed multiple small lesions in the whole brain consistent with a “star field” pattern, including high signals on T2-weighted (T2w) and fluid-attenuated inversion recovery (FLAIR) images in the bilateral centrum semiovale; both frontal, parietal and occipital lobes; and brainstem, cerebellar hemisphere, and deep and subcortical white matter. Intravenous methylprednisolone, heparin, mannitol, antibiotics and nutritional support were used. Although this patient had severe symptoms at first, the outcome was favourable.

Conclusions

When patients have long bone and pelvic fractures, multiple bone fractures and deteriorated neurological status, cerebral fat embolism (CFE) should be considered. Additionally, CFE may occur without an intracardiac shunt. The early diagnosis and appropriate management of FES are important, and prior to and following surgery, patients should be monitored comprehensively in the intensive care unit. With appropriate treatment, CFE patients may achieve good results.
Chronic lymphocytic infiltration with pontine perivascular enhancement responsive to steroids (CLIPPERS) and its association with Epstein‐Barr Virus (EBV)-related lymphomatoid granulomatosis: a case report
Authors: Dang Yew Li , Kok Hong Kuan , McKelvie Penelope A. , Ligtermoet Matthew , Maddy Laura , Burrows David A. , Crompton Douglas E.
Published: February 2021

Background

Chronic lymphocytic infiltration with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a neuro-inflammatory syndrome first described in 2010. It has a relationship with lymphoproliferative disorders that has not been fully elucidated. This case represents an unusual progression of CLIPPERS to Epstein-Barr Virus (EBV)-related lymphomatoid granulomatosis (LYG). The exact connection between CLIPPERS and LYG remains poorly understood.

Case presentation

We present a case of a 75-year-old man who was diagnosed with CLIPPERS with initial response to immunosuppression but later progressed to EBV-related LYG. EBV polymerase chain reaction (PCR) was detected in his cerebrospinal fluid (CSF), and repeat imaging revealed findings that were uncharacteristic for CLIPPERS; thereby prompting a brain biopsy which led to a diagnosis of EBV-related LYG. This case highlights the following learning points: 1) CLIPPERS cases are often part of a spectrum of lymphomatous disease, 2) CLIPPERS can be associated with EBV-related lymphoproliferative disorders such as LYG, and 3) EBV detection in CSF should prompt earlier consideration for brain biopsy in patients.

Conclusions

Our case highlights the difficulty in distinguishing CLIPPERS from other steroid-responsive conditions such as neoplastic and granulomatous diseases. Given the association of CLIPPERS with EBV-related LYG as demonstrated in this case, we recommend testing for EBV in CSF for all patients with suspected CLIPPERS. An early referral for brain biopsy and treatment with rituximab should be considered for patients with suspected CLIPPERS who test positive for EBV in their CSF.
Predictive value of aberrant right subclavian artery for fetal chromosome aneuploidy in women of advanced maternal age
Authors: Chen Li-Ping , Lai Yong-Feng , Zhong Xiao-Hong , You Jian-Hong , Chen Jiang-Hua , Xie Jing-Xian , Chen Xiao-Kang , Chen Xiao-Yan , Lyu Guo-Rong
Published: February 2021

Background

In the entire population, an aberrant right subclavian artery (ARSA) is closely associated with chromosomal abnormalities. ARSA with additional ultrasonic findings would increase risk of chromosomal abnormalities. The risk of fetal chromosomal abnormalities increased exponentially with the maternal age. These risks in the advanced maternal age (AMA) group are uncertain. This study aimed to determine the incidence of ARSA in Chinese AMA and non-AMA women and the frequency of aneuploidy among AMA and non-AMA women with ARSA.

Methods

This retrospective study included 13,690 singleton pregnancies, were divided into AMA and non-AMA groups. Integrated obstetric ultrasonic screening, biochemical screening, noninvasive prenatal screening, and fetal karyotype analysis were analyzed.

Results

The overall incidence of ARSA was 0.69%, with no difference between age groups. The incidence of chromosomal abnormalities in the AMA group (37 / 2860) was much higher than that of the non-AMA group. The risk of chromosomal abnormalities significantly increased with both ARSA detected and additional ultrasound findings. With combined ARSA and AMA, the likelihood of the incidence of chromosomal abnormalities increased. Chimerism (45X / 46XX) was found with isolated ARSA in AMA pregnancies.

Conclusion

There is a high prevalence of chromosomal abnormalities in fetuses of AMA women. ARSA increases the risk of chromosomal abnormalities in both age groups, especially combined with ARSA. When ARSA occurs in AMA women, it confers a high likelihood of chromosomal abnormalities.
Comparison of sonographic fetal weight estimation formulas in patients with preterm premature rupture of membranes
Authors: Warshafsky Chelsie , Ronzoni Stefania , Quaglietta Paula , Weiner Eran , Zaltz Arthur , Barrett Jon , Melamed Nir , Aviram Amir
Published: February 2021

Background

Estimation of fetal weight (EFW) by ultrasound is useful in clinical decision-making. Numerous formulas for EFW have been published but have not been validated in pregnancies complicated by preterm premature rupture of membranes (PPROM). The purpose of this study is to compare the accuracy of EFW formulas in patients with PPROM, and to further evaluate the performance of the most commonly used formula - Hadlock IV.

Methods

A retrospective cohort study of women with singleton gestations and PPROM, admitted to a single tertiary center between 2005 and 2017 from 220/7–330/7 (n = 565). All women had an EFW within 14 days of delivery by standard biometry (biparietal diameter, head circumference, abdominal circumference and femur length). The accuracy of previously published 21 estimated EFW formulas was assessed by comparing the Pearson correlation with actual birth weight, and calculating the random error, systematic error, proportion of estimates within 10% of birth weight, and Euclidean distance.

Results

The mean gestational was 26.8 ± 2.4 weeks at admission, and 28.2 ± 2.6 weeks at delivery. Most formulas were strongly correlated with actual birth weight (r > 0.9 for 19/21 formulas). Mean systematic error was − 4.30% and mean random error was 14.5%. The highest performing formula, by the highest proportion of estimates and lowest Euclidean distance was Ott (1986), which uses abdominal and head circumferences, and femur length. However, there were minimal difference with all of the first 10 ranking formulas. The Pearson correlation coefficient for the Hadlock IV formula was strong at r = 0.935 (p < 0.001), with 319 (56.5%) of measurements falling within 10%, 408 (72.2%) within 15% and 455 (80.5%) within 20% of actual birth weight. This correlation was unaffected by gender (r = 0.936 for males, r = 0.932 for females, p < 0.001 for both) or by amniotic fluid level (r = 0.935 for mean vertical pocket < 2 cm, r = 0.943 for mean vertical pocket ≥2 cm, p < 0.001 for both).

Conclusions

In women with singleton gestation and PPROM, the Ott (1986) formula for EFW was the most accurate, yet all of the top ten ranking formulas performed quite well. The commonly used Hadlock IV performed quite similarly to Ott’s formula, and is acceptable to use in this specific setting.
Intervention fidelity and its determinants of focused antenatal care package implementation, in south Wollo zone, Northeast Ethiopia
Authors: Tessema Asressie Molla , Gebeyehu Abebaw , Mekonnen Solomon , Alemu Kassahun , Tigabu Zemene
Published: February 2021

Background

Focused antenatal care is directed at sustaining maternal health and improving fetal wellbeing to ensure birth of a healthy neonate. Failure to implement focused antenatal care can result in inability to reduce maternal and perinatal morbidity and mortality in low income countries. Due to evidence-practice gaps, however, thousands of maternal, fetal and neonatal lives are still lost every day, mostly from preventable causes. This study aimed to assess focused antenatal care package’s intervention fidelity and its determinant factors in South Wollo Zone, Northeast Ethiopia.

Methods

A cross-sectional study design was employed and a total of 898 women who gave birth in the last 6 months prior to data collection were included. Also 16 health extension workers, working in ten selected health posts, were included. Interviews and self-administered questionnaires were used to collect data from mothers and health extension workers. Ten [10] health posts were audited to assess availability and functionality of drugs and supplies to provide focused antenatal care. Mothers were asked whether or not the required level of care was provided. Health extension workers were provided with self-administered questionnaires to assess socio-demographic characteristics, reception of training, facilitation strategies for the implementation of focused antenatal care and ability to classify danger signs. Multilevel linear regression analysis was performed to identify individual and organizational level’s factors influencing focused antenatal care package intervention fidelity.

Results

Overall weighted average focused antenatal care package intervention fidelity (implemented as intended/planned) was 49.8% (95% CI: 47.7–51.8), which means the average number of focused antenatal care package interventions women received is 49.8%. Health extension workers implemented 55.1% and skilled providers (nurses, midwives, health officers or medical doctors) 44.9% of focused antenatal care package interventions. Overall antenatal care coverage, irrespective of frequency (at least one visit), was 752/898 women (83.7%; 95% CI: 81.3–86.1); 263/752 women (35.0%; 95% CI: 31.6–38.4) received at least four antenatal visits and only 46/752 women (6.1%; 95% CI: 4.4–7.8) received all recommended components of focused antenatal care. Previous pregnancy-related problems, paternal education and implementation of facilitation strategies were found to be significant factors enhancing focused antenatal care package intervention fidelity.

Conclusion

Focused antenatal care package intervention fidelity in the study area was low; this may imply that the current level of maternal, perinatal and neonatal mortality might be partly due to the low level of focused antenatal care intervention fidelity. Improving implementation of facilitation strategies is highly required to contribute to the reduction of those mortalities.
Multidisciplinary tumor boards and their analyses: the yin and yang of outcome measures
Authors: Engelhardt Monika , Ihorst Gabriele , Schumacher Martin , Rassner Michael , Gengenbach Laura , Möller Mandy , Shoumariyeh Khalid , Neubauer Jakob , Farthmann Juliane , Herget Georg , Wäsch Ralph
Published: February 2021

Background

The standard to ensure utmost cancer treatment is a prerequisite in national cancer plans for comprehensive cancer centers (CCCs) and ensured through multidisciplinary tumor boards (MTBs). Despite these being compulsory for CCCs, various analyses on MTBs have been performed, since MTBs are resource-intensive. Outcome measures in these prior analyses had been survival (OS), MTB-adherence and -satisfaction, inclusion of patients into clinical trials and better cancer care.

Main body

A publication from Freytag et al. performed an analysis in multiple tumor entities and assessed the effect of number of MTBs. By matched-pair analysis, they compared response and OS of patients, whose cases were discussed in MTBs vs. those that were not. The analysis included 454 patients and 66 different tumor types. Only patients with > 3 MTBs showed a significantly better OS than patients with no MTB meeting. Response to treatment, relapse free survival and time to progression were not found to be better, nor was there any difference for a specific tumor entity with vs. without MTB discussions.

An in-depth discussion of these results, with respect to the literature (PubMed search: “MTBs AND cancer”) and within the author group, including statisticians specialized in data analysis of cancer patients and questions addressed in MTBs, was performed to interpret these findings. We conclude that the results by Freytag et al. are deceiving due to an “immortal time bias” that requires more careful data interpretation.

Conclusions

The result of Freytag et al. of a seemingly positive impact of higher number of MTBs needs to be interpreted cautiously: their presumed better OS in patients with > 3 MTB discussions is misleading, due to an immortal time bias. Here patients need to survive long enough to be discussed more often. Therefore, these results should not lead to the conclusion that more MTBs will “automatically” increase cancer patients’ OS, rather than that the insightful discussion, at best in MTBs and with statisticians, will generate meaningful advice, that is important for cancer patients.
The effects of colour and temporal frequency of flickering light on variability of the accommodation response in emmetropes and myopes
Authors: Zhang Liyue , Guo Dongyu , Xie Chen , Wen Yingying , Zhang Xuhong , Jin Le , Tong Jianping , Shen Ye
Published: February 2021

Background

Myopia is hypothesized to be influenced by environmental light conditions. For example, it has been shown that colour and temporal frequency of flickering light affect emmetropisation in animals. Considering the omnipresence of flickering light in our daily life, we decided to analyze the effect of colour flickers on variability of the accommodation response (VAR) in emmetropes and myopes.

Methods

We measured the dynamic accommodative responses of 19 emmetropic and 22 myopic adults using a Grand Seiko WAM-5500 open-field autorefractor. The subjects focused for more than 20 s on a black Snellen E target against three different backgrounds made up of three colour flicker combinations (red/green, red/blue and blue/green) and under five frequency conditions (0.20 Hz, 0.50 Hz, 1.00 Hz, 1.67 Hz, and 5.00 Hz).

Results

Flicker frequency and colour both had a significant effect on VAR. Lower frequencies were associated with larger variability. Colour had an effect only at low frequencies, and red/blue colour flicker resulted in the largest variability. The variability in myopes were larger than those in emmetropes.

Conclusions

These findings support the hypothesis that further studies on the colour and temporal frequency of flickering light can lead to a better understanding of the development and progression of myopia.
Treatment outcomes of retinal vein occlusion in clinical practice in Nepal
Authors: Bhandari Sanjeeb , Poudel Manish , Paudyal Indira , Joshi Pratibha L. , Shrestha Chunu , Paudyal Govinda , Pradhan Eli
Published: February 2021

Background

This study evaluated the treatment outcomes of retinal vein occlusion (RVO) in a routine clinical practice in Nepal.

Methods

This was a retrospective analysis of observational data of patients with RVO who attended the retina clinic of the Tilganga Institute of Ophthalmology from 1 November 2017 to 31 October 2018. The main outcome was the mean change in visual acuity (VA) at 12 months from the start of treatment. Other outcomes of interest were the mean change in central subfield thickness (CST) and the number of treatments over 12 months.

Results

A total of 99 eyes (of 99 patients) with RVO (60 - branch RVO [BRVO] and 39 - central RVO [CRVO] were available for the analysis. Eyes with CRVO had worse VA and CST at baseline. Eyes in both groups were similar for age, associated factors for RVO, duration of vision loss and the presence of ischemia at baseline. The mean (95% Confidence Interval [CI]) VA change at 12 months for BRVO was − 0.35 (− 0.46, − 0.23) logMAR (p < 0.001) from a mean (SD) of 0.75 (0.42) logMAR at baseline with 63% achieving VA < 0.3 logMAR while for CRVO it was − 0.35 (− 0.46, − 0.23) logMAR (p = 0.19) from 1.13 (0.61) logMAR at baseline and VA < 0.3 logMAR in 36%. The mean (95% CI) change in CST over 12 months was − 114 (− 189, − 40) μm (p = 0.003) from a mean (SD) of 423 (151) μm at baseline for BRVO and − 184(− 276, − 91) μm (p < 0.001) from 519 (213) μm for CRVO. Patients in both groups received a median of 2 bevacizumab injections over 12 months. Around 37% eyes were lost before 12 months’ observation. The mean VA and CST trajectory in these eyes at their last visit was similar to those that completed 12 months.

Conclusion

The outcomes of RVO over the 12 months were inferior and the number of treatments fewer than those of the clinical trials and other reports from routine clinical practice. Future studies to identify the treatment barriers are warranted to improve the treatment outcomes in our patients.
Partial regression of foveoschisis following vitamin B6 supplementary therapy for gyrate atrophy in a Chinese girl
Authors: Guan Wenxue , Wang Ge , Hu Feng , Peng Xiaoyan
Published: February 2021

Background

To report a case of genetically confirmed gyrate atrophy (GA) of choroid and retina, who showed partial regression of foveoschisis following vitamin B6 supplementary therapy.

Case presentation

A 6-year-old Chinese girl complained about night blindness and progressive decreased vision in both eyes. Her best corrected visual acuity (BCVA) was 20/63 OD and 20/100 OS. Fundus examination showed bilateral multiple, sharply demarcated, scallop-shaped chorioretinal atrophy areas in the midperipheral and peripheral of the fundus. Spectral domain optical coherence tomography (SD-OCT) showed increased central macular thickness (CMT) with multiple intraretinal cystic spaces in the both eyes. There was no leakage or staining in the macular area in late phase of fluorescein angiography (FA). Blood tests confirmed hyperornithinemia and genetic analysis revealed two heterozygous mutations on ornithine aminotransferase (OAT) gene. Based on clinical presentation and genetic test, the patient was diagnosed as GA of the choroid and retina and further treated with vitamin B6 supplementary for three weeks. Her serum ornithine levels did not change but CMT on SD-OCT declined with partial regression of intraretinal cystic spaces. Then, the patient discontinued the drug because of severe muscle pain, and foveoschisis increased to initial level a month later.

Conclusions

Foveoschisis is a rare complication of GA. Vitamin B6 supplementation may alleviate foveoschisis, but its effort for reducing serum ornithine level might be limited. Potential drug adverse effects should be noted in pediatric patients.