bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards the restoration of ancient hominid craniofacial anatomy: Chimpanzee morphology reveals covariation between craniometrics and facial soft tissue thickness
Authors: Campbell Ryan M. , Vinas Gabriel , Henneberg Maciej
Published: June 2021

In modern humans, facial soft tissue thicknesses have been shown to covary with craniometric dimensions. However, to date it has not been confirmed whether these relationships are shared with non-human apes. In this study, we analyze these relationships in chimpanzees (Pan troglodytes) with the aim of producing regression models for approximating facial soft tissue thicknesses in Plio-Pleistocene hominids. Using CT scans of 19 subjects, 637 soft tissue, and 349 craniometric measurements, statistically significant multiple regression models were established for 26 points on the face and head. Examination of regression model validity resulted in minimal differences between observed and predicted soft tissue thickness values. Assessment of interspecies compatibility using a bonobo (Pan paniscus) and modern human subject resulted in minimal differences for the bonobo but large differences for the modern human. These results clearly show that (1) soft tissue thicknesses covary with craniometric dimensions inP.troglodytes, (2) confirms that such covariation is uniformly present in both extantHomoandPanspecies, and (3) suggests that chimp-derived regression models have interspecies compatibility with hominids who have similar craniometric dimensions toP.troglodytes. As the craniometric dimensions of early hominids, such as South African australopithecines, are more similar toP.troglodytesthan those ofH.sapiens, chimpanzee-derived regression models may be used for approximating their craniofacial anatomy. It is hoped that the results of the present study and the reference dataset for facial soft tissue thicknesses of chimpanzees it provides will encourage further research into this topic.
Sablefish (Anoplopoma fimbra Pallas, 1814) plasma biochemistry and hematology reference intervals including blood cell morphology
Authors: Schubiger Carla B. , Gorman M. Elena , Johns Jennifer L. , Arkoosh Mary R. , Dietrich Joseph P.
Published: June 2021

Plasma biochemistry and hematology reference intervals are integral health assessment tools in all medical fields, including aquatic animal health. As sablefish (Anoplopoma fimbria) are becoming aquaculturally and economically more important, this manuscript provides essential reference intervals (RI) for their plasma biochemistry and hematology along with reference photomicrographs of blood cells in healthy, fasted sablefish. Blood cell morphology can differ between fish species. In addition, blood cell counts and blood chemistry can vary between fish species, demographics, water conditions, seasons, diets, and culture systems, which precludes the use of RI’s from other fish species. For this study, blood was collected for plasma biochemistry and hematology analysis between June 20 and July 18, 2019, from healthy, yearling sablefish, hatched and reared in captivity on a commercial diet. Overnight fast of 16–18 hours did not sufficiently reduce lipids in the blood, which led to visible lipemia and frequent rupture of blood cells during analysis. Therefore, sablefish should be fasted for 24 to 36 hours before blood is collected to reduce hematology artifacts or possible reagent interference in plasma biochemistry analysis. Lymphocytes were the most dominant leukocytes (98%), while eosinophils were rare, and basophils were not detected in sablefish. Neutrophils were very large cells with Döhle bodies. In mammals and avian species, Döhle bodies are usually signs of toxic change from inflammation, but no such association was found in these fish. In conclusion, lipemia can interfere with sablefish blood analysis, and available removal methods should be evaluated as fasting for up to 36 h might not always be feasible. Also, more studies are required to establish RI for different developmental stages and rearing conditions.
A panel of 8-lncRNA predicts prognosis of breast cancer patients and migration of breast cancer cells
Authors: Zhu Lili , Cui Kang , Weng Lanling , Yu Pu , Du Yabing , Zhang Tengfei , Liu Hong , Li Bingjie , Ma Wang
Published: June 2021

Background

Breast cancer (BCa) is the most commonly diagnosed cancer and the leading cause of cancer death among females around the world. Recent studies have indicated that long non-coding RNAs (lncRNAs) can serve as an independent biomarker for diagnosis and prognosis in many types of cancer, including pancreatic adenocarcinoma, gastric cancer, liver cancer, and lung cancer. Previous studies have shown that many lncRNAs are associated with the occurrence and development of BCa. However, few studies have combined multiple lncRNAs to predict the prognosis of early-stage BCa patients.

Methods

Systematic and comprehensive analysis of data from The Cancer Genome Atlas (TCGA) was conducted to identify lncRNA signatures with prognostic value in BCa. Additionally, the relative expression levels of the 8 lncRNA of several BCa cell lines were detected by quantitative real-time PCR (qPCR) and the results were substituted into a risk score formula. Finally, migration assays were used to verify the result from prognostic analysis according to the risk scores among cell lines with different risk scores.

Results

Our study included 808 BCa patients with complete clinical data. A panel of 8 lncRNAs was identified using Wilcox tests as different between normal and tumor tissue of the BCa patients. This panel was used to analyze the survival of BCa patients. Patients with low risk scores had greater overall survival (OS) than those with high risk scores. Multivariate Cox regression analyses demonstrated that the lncRNA signature was an independent prognostic factor. Gene Set Enrichment Analysis (GSEA) suggested that the lncRNAs might be involved in several molecular signaling pathways implicated in BCa such as the DNA replication pathway, the cell cycle pathway, and the pentose phosphate pathway. Validation experiments in breast cancer cells to test cell migration by using wound-healing assays supported the results of the model.

Conclusion

Our study demonstrated that a panel of 8 lncRNAs has the potential to be used as an independent prognostic biomarker of BCa.
Colorectal cancer in patients with single versus double positive faecal immunochemical test results: A retrospective cohort study from a public tertiary hospital
Authors: Lim Tian Zhi , Lau Jerrald , Wong Gretel Jianlin , Tan Ker-Kan
Published: June 2021

Background

Screening for colorectal cancer (CRC) using the faecal immunochemical test (FIT) is widely advocated. Few studies have compared the rate of detecting colonoscopic pathologies in single compared to double FIT-positive follow-up colonoscopy-compliant individuals in a two-sample national FIT screening program.

Objective

To compare CRC incidence in double FIT-positive versus single FIT-positive individuals using a retrospective cohort of patients from a tertiary hospital in Singapore.

Design

Retrospective cohort study.

Setting

Data was extracted from one public tertiary hospital in Singapore.

Participants

1,422 FIT-positive individuals from the national FIT screening program who were referred to the hospital from 1st January 2017 to 31st March 2020 for follow-up consultation and diagnostic colonoscopy.

Measurements

The exposure of interest was a positive result on both FIT kits. The main outcome was a follow-up diagnostic colonoscopy finding of CRC. The secondary outcome was a diagnostic colonoscopy finding of a colorectal polyp.

Results

Incidence density of CRC was 1.15 and 13.10 per 100,000 person-months, in the single and double FIT-positive group, respectively. This resulted in an incidence rate ratio of 11.40 (95% CI = 4.34, 35.09). Colorectal polyp detection was significantly higher (p < 0.01) in the double (103 of 173 participants; 59.5%) compared to the single (279 of 671 participants; 41.6%) FIT-positive group.

Limitations

The key limitation of this study was the relatively small cohort derived from a single tertiary hospital, as this had the effect of limiting the number of incident cases, resulting in comparatively imprecise CIs.

Conclusions

Double FIT-positive individuals are significantly more likely to have a colonoscopy finding of incident CRC or premalignant polyp than single FIT-positive individuals. Clinicians and policymakers should consider updating their CRC screening protocols accordingly.
Study on ageing characteristics and evaluation methods of RTV silicone rubber in high humidity area
Authors: Yang Hao , Wen Ran , Zhao Heng , Guo Men , Zhang Lu , Chen Yu
Published: June 2021

Due to high humidity, the ageing of room temperature vulcanized silicone rubber (RTV) has been a serious problem in Southwestern China. In order to solve the problem of RTV life prediction, the aging classification method was established by analyzing the microtopography of RTV samples in this paper. Besides, the comprehensive analysis of RTV element content, partial element content ratio, and major chemical groups of RTV samples in each aging level were conducted. It is found that as the ageing level increases, the element contents of C, Si, O, Al change accordingly and the ratio of C:Si drops from 2.39 to 1.54, and absorption peaks of the chemical groups of Si-(CH3)2, Si-O-Si, Si-CH3 and C-H in CH3 decrease. This work can enrich the investigation of RTV, and may provide useful reference for performance evaluation and replacement of RTV in substations.
Detection of genotype-1 of dengue virus serotype 3 for the first time and complete genome analysis of dengue viruses during the 2018 epidemic in Mandalay, Upper Myanmar
Authors: Ngwe Tun Mya Myat , Kyaw Aung Kyaw , Nabeshima Takeshi , Soe Aung Min , Nwe Khine Mya , Htet Kyaw Ko Ko , Aung Thet Htoo , Htwe Thein Thein , Aung Thidar , Myaing Su Su , Mar Tu Tu , Lwin Ei Phyu , Thu Hlaing Myat , Thant Kyaw Zin , Morita Kouichi
Published: June 2021

Background

Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the emergence of new genotypes and serotype shifting.

Methodology and principal findings

To understand the genomic and viral characteristics of DENV-infected patients, we conducted a cross-sectional descriptive study among pediatric patients admitted at the 550-bedded Mandalay Children Hospital during the 2018 DEN endemic season. We conducted virus isolation, serological tests, viremia level measurement, and whole-genome sequencing. Among the 202 serum samples, we detected 85 samples with DENV (46 DENV-1, 10 DENV-3, 26 DENV-4 and three multiple serotype co-infections) via reverse transcription quantitative/real-time PCR (RT-qPCR), and we obtained 49 DENV isolates (31 DENV-1, 10 DENV-3 and 8 DEN-4). We did not detect DENV-2 in this study. The viral genome levels in serum did not differ significantly among virus serotypes, infection status (primary versus secondary) and disease severity. Based on the phylogenetic analysis, we identified DENV-1 genotype-1, DENV-4 genotype-1 and DENV-3 genotype-3 and genotype-1 which was detected for the first time. Next-generation sequencing analysis revealed greater frequencies of nonsynonymous and synonymous mutations per gene in the nonstructural genes. Moreover, mutation rates were also higher among DENV-1.

Conclusion/Significance

In conclusion, there was an increasing trend of DENV-3 cases during DENV endemic season in 2018 with the first detection of the genotype 1. However, DENV-1 has remained the predominant serotype in this study area since 2013, and we identified stop codon mutations in the DENV-1 genome. This report is the first to feature a complete genome analysis of the strains of DENV-3 and DENV-4 circulating among pediatric patients in Myanmar. This study highlighted the importance of annual surveillance for a better understanding of the molecular epidemiology of DENVs.
A single patient reported outcome measure for acquired brain injury, multiple sclerosis & Parkinson’s disease
Authors: Carter Ben , Hayes Chloe , Smith Alexander , Pennington Anna , Price Michelle , Pearson Owen , Vitoratou Silia , Hewitt Jonathan
Published: June 2021

Objective

To determine psychometric properties of the PROMIS-10 and Standard Stroke Question Set (by International Consortium for Health Outcome Measures) presented as a new 15-item Patient Related Outcome (PRO), for patients with: acquired Brain Injury (ABI), Multiple sclerosis (MS) and Parkinson’s disease (PD).

Methods

In an eight centre, UK wide, cross-sectional study we approached patients during their routine follow-up to complete: a disease-specific instrument (European Brain Injury Questionnaire, Multiple Sclerosis Impact Scale, and Parkinson’s disease questionnaire); General Health questionnaire with a Quality of life measure (EQ-5D); and PRO. We validated the PRO using factor analysis to define the latent construct domains, then calculated the internal consistency (Cronbach’s-α), and construct validity (correlation).

Results

There were 340 patients with ABI (N = 91, median age = 55.1, 41% female), MS (N = 99, age = 58.9, 69%) and PD (N = 150, age = 74.5, 40%). Factor analysis suggested the PRO offered three domains of: physical health; functionality-capacity and mental health. All factors correlated strongly with the three disease-specific instruments, and the overall PRO had a large correlation with the EQ-5D (correlation>0.8) offering good construct validity and excellent internal consistency (∝>0.89).

Interpretation

The PRO offered promising psychometric properties and could be used in place of disease specific questionnaires for patients with ABI, MS, and PD. The PRO has three construct domains, describing patients’: mental health; physical health; and functional-capacity, and may be used in routine clinical practice. The PRO offered both relevance to each of the three separate neurological conditions and generalisability across all the conditions, increasing its utility.
Familial Hypercholesterolemia in the Arabian Gulf Region: Clinical results of the Gulf FH Registry
Authors: Alhabib Khalid F. , Al-Rasadi Khalid , Almigbal Turky H. , Batais Mohammed A. , Al-Zakwani Ibrahim , Al-Allaf Faisal A. , Al-Waili Khalid , Zadjali Fahad , Alghamdi Mohammad , Alnouri Fahad , Awan Zuhier , Kinsara Abdulhalim J. , AlQudaimi Ahmed , Almahmeed Wael , Sabbour Hani , Traina Mahmoud , Atallah Bassam , Al-Jarallah Mohammed , AlSarraf Ahmad , AlSayed Nasreen , Amin Haitham , Altaradi Hani
Published: June 2021

Background and aims

Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf countries (Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain).

Methods

The multicentre, multinational Gulf FH registry included adults (≥18 years old) recruited from outpatient clinics in 14 tertiary-care centres across five Arabian Gulf countries over the last five years. The Gulf FH registry had four phases: 1- screening, 2- classification based on the Dutch Lipid Clinic Network, 3- genetic testing, and 4- follow-up.

Results

Among 34,366 screened patient records, 3713 patients had suspected FH (mean age: 49±15 years; 52% women) and 306 patients had definite or probable FH. Thus, the estimated FH prevalence was 0.9% (1:112). Treatments included high-intensity statin therapy (34%), ezetimibe (10%), and proprotein convertase subtilisin/kexin type 9 inhibitors (0.4%). Targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol were achieved by 12% and 30%, respectively, of patients at high ASCVD risk, and by 3% and 6%, respectively, of patients at very high ASCVD risk (p <0.001; for both comparisons).

Conclusions

This snap-shot study was the first to show the high estimated prevalence of FH in the Arabian Gulf region (about 3-fold the estimated prevalence worldwide), and is a “call-to-action” for further confirmation in future population studies. The small proportions of patients that achieved target LDL-C values implied that health care policies need to implement nation-wide screening, raise FH awareness, and improve management strategies for FH.
Coarse woody debris decomposition assessment tool: Model development and sensitivity analysis
Authors: Dai Zhaohua , Trettin Carl C. , Burton Andrew J. , Jurgensen Martin F. , Page-Dumroese Deborah S. , Forschler Brian T. , Schilling Jonathan S. , Lindner Daniel L.
Published: June 2021

Coarse woody debris (CWD) is an important component in forests, hosting a variety of organisms that have critical roles in nutrient cycling and carbon (C) storage. We developed a process-based model using literature, field observations, and expert knowledge to assess woody debris decomposition in forests and the movement of wood C into the soil and atmosphere. The sensitivity analysis was conducted against the primary ecological drivers (wood properties and ambient conditions) used as model inputs. The analysis used eighty-nine climate datasets from North America, from tropical (14.2° N) to boreal (65.0° N) zones, with large ranges in annual mean temperature (26.5°C in tropical to -11.8°C in boreal), annual precipitation (6,143 to 181 mm), annual snowfall (0 to 612 kg m-2), and altitude (3 to 2,824 m above mean see level). The sensitivity analysis showed that CWD decomposition was strongly affected by climate, geographical location and altitude, which together regulate the activity of both microbial and invertebrate wood-decomposers. CWD decomposition rate increased with increments in temperature and precipitation, but decreased with increases in latitude and altitude. CWD decomposition was also sensitive to wood size, density, position (standing vs downed), and tree species. The sensitivity analysis showed that fungi are the most important decomposers of woody debris, accounting for over 50% mass loss in nearly all climatic zones in North America. The model includes invertebrate decomposers, focusing mostly on termites, which can have an important role in CWD decomposition in tropical and some subtropical regions. The role of termites in woody debris decomposition varied widely, between 0 and 40%, from temperate areas to tropical regions. Woody debris decomposition rates simulated for eighty-nine locations in North America were within the published range of woody debris decomposition rates for regions in northern hemisphere from 1.6° N to 68.3° N and in Australia.
ACRBP (Sp32) is involved in priming sperm for the acrosome reaction and the binding of sperm to the zona pellucida in a porcine model
Authors: Kato Yoku , Kumar Satheesh , Lessard Christian , Bailey Janice L.
Published: June 2021

In boar sperm, we have previously shown that capacitation is associated with the appearance of the p32 tyrosine phosphoprotein complex. The principal tyrosine phosphoprotein involved in this complex is the acrosin-binding protein (ACRBP), which regulates the autoconversion of proacrosin to intermediate forms of acrosin in both boar and mouse sperm. However, the complete biological role of ACRBP has not yet been elucidated. In this study, we tested the hypothesis that tyrosine phophorylation and the presence of the ACRBP in the sperm head are largely necessary to induce capacitation, the acrosome reaction (AR) and sperm-zona pellucida (ZP) binding, all of which are necessary steps for fertilization.In vitrofertilization (IVF) was performed using matured porcine oocytes and pre-capacitated boar sperm cultured with anti-phosphotyrosine antibodies or antibodies against ACRBP. Anti-ACRBP antibodies reduced capacitation and spontaneous AR (P<0.05). Sperm-ZP binding declined in the presence of anti-phosphotyrosine or anti-ACRBP antibodies. The localisation of anti-ACRBP antibodies on the sperm head, reduced the ability of the sperm to undergo the AR in response to solubilized ZP or by inhibiting the sarco/endoplasmic reticulum Ca2+-ATPase. These results support our hypothesis that tyrosine phosphorylated proteins and ACRBP are present upon the sperm surface in order to participate in sperm-ZP binding, and that ACRBP upon the surface of the sperm head facilitates capacitation and the AR in the porcine.
New models for donor-recipient matching in lung transplantations
Authors: Dueñas-Jurado J. M. , Gutiérrez P. A. , Casado-Adam A. , Santos-Luna F. , Salvatierra-Velázquez A. , Cárcel S. , Robles-Arista C. J. C. , Hervás-Martínez C.
Published: June 2021

Objective

One of the main problems of lung transplantation is the shortage of organs as well as reduced survival rates. In the absence of an international standardized model for lung donor-recipient allocation, we set out to develop such a model based on the characteristics of past experiences with lung donors and recipients with the aim of improving the outcomes of the entire transplantation process.

Methods

This was a retrospective analysis of 404 lung transplants carried out at the Reina Sofía University Hospital (Córdoba, Spain) over 23 years. We analyzed various clinical variables obtained via our experience of clinical practice in the donation and transplantation process. These were used to create various classification models, including classical statistical methods and also incorporating newer machine-learning approaches.

Results

The proposed model represents a powerful tool for donor-recipient matching, which in this current work, exceeded the capacity of classical statistical methods. The variables that predicted an increase in the probability of survival were: higher pre-transplant and post-transplant functional vital capacity (FVC), lower pre-transplant carbon dioxide (PCO2) pressure, lower donor mechanical ventilation, and shorter ischemia time. The variables that negatively influenced transplant survival were low forced expiratory volume in the first second (FEV1) pre-transplant, lower arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio, bilobar transplant, elderly recipient and donor, donor-recipient graft disproportion requiring a surgical reduction (Tailor), type of combined transplant, need for cardiopulmonary bypass during the surgery, death of the donor due to head trauma, hospitalization status before surgery, and female and male recipient donor sex.

Conclusions

These results show the difficulty of the problem which required the introduction of other variables into the analysis. The combination of classical statistical methods and machine learning can support decision-making about the compatibility between donors and recipients. This helps to facilitate reliable prediction and to optimize the grafts for transplantation, thereby improving the transplanted patient survival rate.
The disproportion of crowd wisdom: The impact of status seeking on Yelp reviews
Authors: Yu Chao , Margolin Drew
Published: June 2021

This study shows that while status seeking motivates people to participate in crowdsourcing platforms, it also negatively impacts the bedrock of crowdsourcing–wisdom of crowds. Using Yelp restaurant reviews in 6 cities, we found that motivations of status seeking lead people to review a greater variety of restaurants, and achieving status further encourages this variety seeking as well as the targeting of more expensive restaurants for review. The impact of this individual-level tendency is confirmed by our aggregate-level analysis which shows that restaurants with higher price levels, higher uniqueness levels, and a larger percentage of elite reviews tend to obtain enough reviews to generate wisdom of crowds sooner than other restaurants. This leads to a different kind of distortion to crowd wisdom: an over-representation of status-conferring products and an under-representation of products that are not status-worthy. The findings suggest the importance of studying sources of distortion that are endemic to crowdsourcing itself.
High TB burden and low notification rates in the Philippines: The 2016 national TB prevalence survey
Authors: Lansang Mary Ann D. , Alejandria Marissa M. , Law Irwin , Juban Noel R. , Amarillo Maria Lourdes E. , Sison Olivia T. , Cruz Jose Rene B. , Ang Concepcion F. , Buensalido Joseph Adrian L. , Cañal Johanna Patricia A. , Castillo-Carandang Nina T. , Cordero Cynthia P. , Gaviola Donna Mae G. , Ladia Mary Ann J. , Mantaring Jacinto Blas V. , Mendoza Myrna T. , Salamat Maria Sonia S. , Lam Hilton Y. , Tadolini Marina , Garfin Anna Marie Celina G. ,   Philippine NTPS 2016 Group
Published: June 2021

Setting

The 3rd national tuberculosis (TB) survey in the Philippines in 2007 reported a significant decline in the prevalence of TB. Since then, more significant investments for TB control have been made, yet TB burden estimates from routine surveillance data remain relatively stable.

Objective

To estimate the prevalence of bacteriologically confirmed pulmonary TB in the Philippines amongst individuals aged ≥15 years in 2016.

Design

In March–December 2016, we conducted a population-based survey with stratified, multi-stage cluster sampling of residents in 106 clusters aged ≥15 years. Survey participants were screened for TB by symptom-based interview and digital chest X-ray. Those with cough ≥2 weeks and/or haemoptysis and/or chest X-ray suggestive of TB were requested to submit 2 sputum specimens for Xpert MTB/RIF, direct sputum smear microscopy using LED fluorescent microscopy, and mycobacterial solid culture (Ogawa method). Bacteriologically confirmed pulmonary TB was defined as MTB culture positive and/or Xpert positive.

Results

There were 46,689 individuals interviewed, and 41,444 (88.8%) consented to a chest X-ray. There were 18,597 (39.8%) eligible for sputum examination and 16,242 (87.3%) submitted at least one specimen. Out of 16,058 sputum-eligible participants, 183 (1.1%) were smear-positive. There were 466 bacteriologically confirmed TB cases: 238 (51.1%) Xpert positive, 69 (14.8%) culture positive, and 159 (34.1%) positive by both Xpert and culture. The estimated TB prevalence per 100,000 population aged ≥15 years was 434 (95% CI: 350−518) for smear-positive TB, and 1,159 (95% CI: 1,016−1,301) for bacteriologically confirmed TB.

Conclusion

This nationally representative survey found that the TB burden in the Philippines in 2016 was higher than estimated from routine TB surveillance data. There was no evidence of a decline in smear and culture positive TB from the 2007 survey despite significant investments in TB control. New strategies for case-finding and patient-centered care must be intensified and expanded.
Inferring spikes from calcium imaging in dopamine neurons
Authors: Fleming Weston , Jewell Sean , Engelhard Ben , Witten Daniela M. , Witten Ilana B.
Published: June 2021

Calcium imaging has led to discoveries about neural correlates of behavior in subcortical neurons, including dopamine (DA) neurons. However, spike inference methods have not been tested in most populations of subcortical neurons. To address this gap, we simultaneously performed calcium imaging and electrophysiology in DA neurons in brain slices and applied a recently developed spike inference algorithm to the GCaMP fluorescence. This revealed that individual spikes can be inferred accurately in this population. Next, we inferred spikes in vivo from calcium imaging from these neurons during Pavlovian conditioning, as well as during navigation in virtual reality. In both cases, we quantitatively recapitulated previous in vivo electrophysiological observations. Our work provides a validated approach to infer spikes from calcium imaging in DA neurons and implies that aspects of both tonic and phasic spike patterns can be recovered.
Evaluation of laser induced sarcomere micro-damage: Role of damage extent and location in cardiomyocytes
Authors: Müller Dominik , Klamt Thorben , Gentemann Lara , Heisterkamp Alexander , Kalies Stefan Michael Klaus
Published: June 2021

Whereas it is evident that a well aligned and regular sarcomeric structure in cardiomyocytes is vital for heart function, considerably less is known about the contribution of individual elements to the mechanics of the entire cell. For instance, it is unclear whether altered Z-disc elements are the reason or the outcome of related cardiomyopathies. Therefore, it is crucial to gain more insight into this cellular organization. This study utilizes femtosecond laser-based nanosurgery to better understand sarcomeres and their repair upon damage. We investigated the influence of the extent and the location of the Z-disc damage. A single, three, five or ten Z-disc ablations were performed in neonatal rat cardiomyocytes. We employed image-based analysis using a self-written software together with different already published algorithms. We observed that cardiomyocyte survival associated with the damage extent, but not with the cell area or the total number of Z-discs per cell. The cell survival is independent of the damage position and can be compensated. However, the sarcomere alignment/orientation is changing over time after ablation. The contraction time is also independent of the extent of damage for the tested parameters. Additionally, we observed shortening rates between 6–7% of the initial sarcomere length in laser treated cardiomyocytes. This rate is an important indicator for force generation in myocytes. In conclusion, femtosecond laser-based nanosurgery together with image-based sarcomere tracking is a powerful tool to better understand the Z-disc complex and its force propagation function and role in cellular mechanisms.
Characterization of dysphagia and laryngeal findings in COVID-19 patients treated in the ICU—An observational clinical study
Authors: Osbeck Sandblom Hanna , Dotevall Hans , Svennerholm Kristina , Tuomi Lisa , Finizia Caterina
Published: June 2021

Background

Dysphagia appears to be common in patients with severe COVID-19. Information about the characteristics of dysphagia and laryngeal findings in COVID-19 patients treated in the intensive care unit (ICU) is still limited.

Objectives

The aim of this study was to evaluate oropharyngeal swallowing function and laryngeal appearance and function in patients with severe COVID-19.

Method

A series of 25 ICU patients with COVID-19 and signs of dysphagia were examined with fiberendoscopic evaluation of swallowing (FEES) during the latter stage of ICU care or after discharge from the ICU. Swallowing function and laryngeal findings were assessed with standard rating scales from video recordings.

Results

Pooling of secretions was found in 92% of patients. Eleven patients (44%) showed signs of silent aspiration to the trachea on at least one occasion. All patients showed residue after swallowing to some degree both in the vallecula and hypopharynx. Seventy-six percent of patients had impaired vocal cord movement. Erythema of the vocal folds was found in 60% of patients and edema in the arytenoid region in 60%.

Conclusion

Impairment of oropharyngeal swallowing function and abnormal laryngeal findings were common in this series of patients with severe COVID-19 treated in the ICU. To avoid complications related to dysphagia in this patient group, it seems to be of great importance to evaluate the swallowing function as a standard procedure, preferably at an early stage, before initiation of oral intake. Fiberendoscopic evaluation of swallowing is preferred due to the high incidence of pooling of secretion in the hypopharynx, silent aspiration, and residuals. Further studies of the impact on swallowing function in short- and long-term in patients with COVID-19 are warranted.
Metabolic alterations and systemic inflammation in overweight/obese children with obstructive sleep apnea
Authors: Bhatt Surya Prakash , Guleria Randeep , Kabra S. K.
Published: June 2021

Aim and objective

Systemic inflammation has been documented in obstructive sleep apnea (OSA). However studies on childhood OSA and systemic inflammation are limited. This study aimed to determine the relation between OSA in overweight/obese children and various inflammatory markers.

Material and methods

In this cross sectional study, we enrolled 247 overweight/ obese children from pediatric outpatient services. We evaluated demographic and clinical details, anthropometric parameters, body composition and estimation of inflammatory cytokines such as interleukin (IL) 6, IL-8, IL-10, IL-17, IL-18, IL-23, macrophage migration inhibitory factor (MIF), high sensitive C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1) and leptin levels. Overnight polysomnography was performed.

Findings

A total of 247 children (190 with OSA and 57 without OSA) were enrolled. OSA was documented on polysomnography in 40% of patients. We observed significantly high values body mass index, waist circumference (WC), % body fat, fasting blood glucose (FBG), alanine transaminase (ALT), alkaline phosphate, fasting insulin and HOMA-IR in children with OSA. Inflammatory markers IL-6, IL-8, IL-17, IL-18, MIF, Hs CRP, TNF- α, PAI-1, and leptin levels were significantly higher in OSA patients (p<0.05). There was strong positive correlation of IL-6, IL-8, IL-17, IL-23, MIF, Hs CRP, TNF-A, PAI-1 and leptin with BMI, % body fat, AHI, fasting Insulin, triglyceride, FBG, WC, HOMA-IR, AST and ALT.

Conclusion

Children with OSA have increased obesity, insulin resistance and systemic inflammation. Further studies are require to confirm our findings and evaluate their utility in diagnosis of OSAs, assessing severity and possible interventions.
Greater travel distance to specialized facilities is associated with higher survival for patients with soft-tissue sarcoma: US nationwide patterns
Authors: Fujiwara Tomohiro , Ogura Koichi , Healey John
Published: June 2021

Purpose

The survival impact of geographic access to specialized care remains unknown in patients with soft-tissue sarcomas (STS). This study aimed to clarify the association between the patient travel distance and survival outcome and investigate the factors lying behind it.

Methods

A total of 34 528 patients with STS registered in the National Cancer Data Base, diagnosed from 2004–2016, were investigated.

Results

Tumor stage correlated with travel distance: patients with metastatic disease stayed closer to home. However, the type of facility showed greatest variation: 37.0%, 51.0%, 73.5%, and 75.9% of patients with ≤10 miles, 10.1–50 miles, 50.1–100 miles, and >100 miles, respectively (P<0.001), had a sarcoma care at academic/research centers. On a multivariable analysis, reduced mortality risk was associated with longer (versus short) travel distance (>100 miles: HR = 0.877; P = 0.001) and management at academic/research (versus non-academic/research) centers (HR = 0.857; P<0.001). The greatest divergence was seen in patients traveling very long distance (>100 miles) to an academic/research center, with a 26.9% survival benefit (HR = 0.731; P<0.001), compared with those traveling short distance (≤10 miles; 95.4% living in metropolitan area) to a non-academic/research center. There was no significant correlation between travel distance and survival in patients who had care at academic/research centers, whereas a survival benefit of management at academic/research centers was observed in every group of travel distance, regardless of tumor stage.

Conclusions

This national study demonstrated that increased travel distance was associated with superior survival, attributable to a higher proportion of patients receiving sarcoma care at distant academic/research centers. These data support centralized care for STS. Overcoming referral and travel barriers may enable more patients to be treated at specialized centers and may further improve survival rates for patients with STS, even when it imposes an increased travel burden.
Health and economic costs of early and delayed suppression and the unmitigated spread of COVID-19: The case of Australia
Authors: Kompas Tom , Grafton R. Quentin , Che Tuong Nhu , Chu Long , Camac James
Published: June 2021

We compare the health and economic costs of early and delayed mandated suppression and the unmitigated spread of ‘first-wave’ COVID-19 infections in Australia in 2020. Using a fit-for-purpose SIQRM-compartment model for susceptible, infected, quarantined, recovered and mortalities on active cases, that we fitted from recorded data, a value of a statistical life year (VSLY) and an age-adjusted value of statistical life (A-VSL), we find that the economic costs of unmitigated suppression are multiples more than for early mandated suppression. We also find that using an equivalent VSLY welfare loss from fatalities to estimated GDP losses, drawn from survey data and our own estimates of the impact of suppression measures on the economy, means that for early suppression not to be the preferred strategy requires that Australia would have to incur more than 12,500–30,000 deaths, depending on the fatality rate with unmitigated spread, to the economy costs of early mandated suppression. We also find that early rather than delayed mandated suppression imposes much lower economy and health costs and conclude that in high-income countries, like Australia, a ‘go early, go hard’ strategy to suppress COVID-19 results in the lowest estimated public health and economy costs.
Differences in levels of phosphatidylinositols in healthy and stable Coronary Artery Disease subjects revealed by HILIC-MRM method with SERRF normalization
Authors: Huang Yue , Mu Ruipeng , Wen David , Grimsby Joseph S. , Liang Meina , Rosenbaum Anton I.
Published: June 2021

Quantification of endogenous biomarkers in clinical studies requires careful evaluation of a number of assay performance parameters. Comparisons of absolute values from several clinical studies can enable retrospective analyses further elucidating the biology of a given biomarker across various study populations. We characterized the performance of a highly multiplex bioanalytical method for quantification of phosphatidylinositols (PI). Hydrophilic interaction chromatography (HILIC) and multiple reaction monitoring (MRM) were employed for targeted multiplex quantification. Odd-chain PI species that are not normally present in human plasma were utilized as surrogate analytes (SA) to assess various assay performance parameters and establish a definitive dynamic linear range for PI lipids. To correct for batch effects, Systematic Error Removal using Random Forest (SERRF) normalization algorithm was employed and used to bridge raw values between two clinical studies, enabling quantitative comparison of their absolute values. A high throughput method was developed, qualified, transferred to an automation platform and applied to sample testing in two clinical trials in healthy volunteers (NCT03001297) and stable Coronary Artery Disease (CAD, NCT03351738) subjects. The method demonstrated acceptable precision and accuracy (±30%) over linear range of 1–1000 nM for SA and 8-fold dilutional linearity for endogenous PI. We determined that mean-adjusted average QC performed best for normalization using SERRF. The comparison of two studies revealed that healthy subject levels of PI are consistently higher across PI species compared to CAD subjects identifying a potential lipid biomarker to be explored in future studies.
DUNEuro—A software toolbox for forward modeling in bioelectromagnetism
Authors: Schrader Sophie , Westhoff Andreas , Piastra Maria Carla , Miinalainen Tuuli , Pursiainen Sampsa , Vorwerk Johannes , Brinck Heinrich , Wolters Carsten H. , Engwer Christian
Published: June 2021

Accurate and efficient source analysis in electro- and magnetoencephalography using sophisticated realistic head geometries requires advanced numerical approaches. This paper presents DUNEuro, a free and open-source C++ software toolbox for the numerical computation of forward solutions in bioelectromagnetism. Building upon the DUNE framework, it provides implementations of modern fitted and unfitted finite element methods to efficiently solve the forward problems of electro- and magnetoencephalography. The user can choose between a variety of different source models that are implemented. The software’s aim is to provide interfaces that are extendable and easy-to-use. In order to enable a closer integration into existing analysis pipelines, interfaces to Python and MATLAB are provided. The practical use is demonstrated by a source analysis example of somatosensory evoked potentials using a realistic six-compartment head model. Detailed installation instructions and example scripts using spherical and realistic head models are appended.
High pre-pregnancy BMI with a history of gestational diabetes mellitus is associated with an increased risk of type 2 diabetes in Korean women
Authors: Shin Dayeon , Lee Kyung Won
Published: June 2021

Despite the importance of pre-pregnancy body mass index (BMI) and a history of gestational diabetes mellitus (GDM) in the progression of GDM to type 2 diabetes, few studies have evaluated the combined effect of high pre-pregnancy BMI and GDM status on the future development of type 2 diabetes in Korean women. This study aimed to examine the relationship of pre-pregnancy BMI and GDM history with the risk of type 2 diabetes among Korean women. In addition, the effects of pre-pregnancy BMI and current BMI on the risk of type 2 diabetes were evaluated. Women who gave birth in the Health Examinees Study of the Korean Genome and Epidemiology Study from 2004 to 2013 (n = 59,258) were included in this study. Multivariable logistic regression was used to examine the association of pre-pregnancy BMI categories (underweight: <18.5 kg/m2; normal: 18.5–22.9 kg/m2; overweight: 23.0–24.9 kg/m2; obese: ≥25.0 kg/m2) and GDM history with the risk of type 2 diabetes after controlling for the following covariates: age, education, income, smoking status before the first pregnancy, alcohol consumption, regular exercise, menarche age, first pregnancy age, and first pregnancy outcome. Compared to women with normal pre-pregnancy BMIs, women with overweight and obese pre-pregnancy BMIs had higher odds of developing type 2 diabetes (adjusted odds ratio [AOR]: 1.13, 95% confidence interval [CI]: 1.02–1.25 and AOR: 1.29, 95% CI: 1.10–1.50, respectively) after controlling for covariates. Women with pre-pregnancy BMIs <23 kg/m2 and current BMIs ≥23 kg/m2 had increased odds of developing type 2 diabetes (AOR: 1.64, 95% CI: 1.51–1.78) compared to those with pre-pregnancy BMIs <23 kg/m2 and current BMIs <23 kg/m2. Among women without a history of GDM, those with overweight and obese pre-pregnancy BMIs had increased odds of developing type 2 diabetes compared to those with normal pre-pregnancy BMIs (AOR: 1.12, 95% CI: 1.01–1.24 and AOR: 1.23, 95% CI: 1.05–1.44, respectively). Among women with GDM, those with obese pre-pregnancy BMIs had increased odds of developing type 2 diabetes (AOR: 3.84, 95% CI: 1.52–9.87). This study showed that there was a higher likelihood of developing type 2 diabetes in women who were overweight or obese before pregnancy with a history of GDM compared to their counterparts without a history of GDM. Furthermore, high pre-pregnancy BMI or high current BMI increased the risk of type 2 diabetes in Korean women, regardless of GDM history. This emphasizes the importance of maintaining a healthy weight status before and after pregnancy to prevent the future risk of type 2 diabetes.
Excess mortality associated with the COVID-19 pandemic among Californians 18–65 years of age, by occupational sector and occupation: March through November 2020
Authors: Chen Yea-Hung , Glymour Maria , Riley Alicia , Balmes John , Duchowny Kate , Harrison Robert , Matthay Ellicott , Bibbins-Domingo Kirsten
Published: June 2021

Background

Though SARS-CoV-2 outbreaks have been documented in occupational settings and in-person essential work has been suspected as a risk factor for COVID-19, occupational differences in excess mortality have, to date, not been examined. Such information could point to opportunities for intervention, such as vaccine prioritization or regulations to enforce safer work environments.

Methods and findings

Using autoregressive integrated moving average models and California Department of Public Health data representing 356,188 decedents 18–65 years of age who died between January 1, 2016 and November 30, 2020, we estimated pandemic-related excess mortality by occupational sector and occupation, with additional stratification of the sector analysis by race/ethnicity. During these first 9 months of the COVID-19 pandemic, working-age adults experienced 11,628 more deaths than expected, corresponding to 22% relative excess and 46 excess deaths per 100,000 living individuals. Sectors with the highest relative and per-capita excess mortality were food/agriculture (39% relative excess; 75 excess deaths per 100,000), transportation/logistics (31%; 91 per 100,000), manufacturing (24%; 61 per 100,000), and facilities (23%; 83 per 100,000). Across racial and ethnic groups, Latino working-age Californians experienced the highest relative excess mortality (37%) with the highest excess mortality among Latino workers in food and agriculture (59%; 97 per 100,000). Black working-age Californians had the highest per-capita excess mortality (110 per 100,000), with relative excess mortality highest among transportation/logistics workers (36%). Asian working-age Californians had lower excess mortality overall, but notable relative excess mortality among health/emergency workers (37%), while White Californians had high per-capita excess deaths among facilities workers (70 per 100,000).

Conclusions

Certain occupational sectors are associated with high excess mortality during the pandemic, particularly among racial and ethnic groups also disproportionately affected by COVID-19. In-person essential work is a likely venue of transmission of coronavirus infection and must be addressed through vaccination and strict enforcement of health orders in workplace settings.