bluuebunny/crossref_metadata_2025 huggingface dataset:
A multistate competing risks framework for preconception prediction of pregnancy outcomes
Authors: Cook Kaitlyn , Perkins Neil J. , Schisterman Enrique , Haneuse Sebastien
Published: May 2022

Background

Preconception pregnancy risk profiles—characterizing the likelihood that a pregnancy attempt results in a full-term birth, preterm birth, clinical pregnancy loss, or failure to conceive—can provide critical information during the early stages of a pregnancy attempt, when obstetricians are best positioned to intervene to improve the chances of successful conception and full-term live birth. Yet the task of constructing and validating risk assessment tools for this earlier intervention window is complicated by several statistical features: the final outcome of the pregnancy attempt is multinomial in nature, and it summarizes the results of two intermediate stages, conception and gestation, whose outcomes are subject to competing risks, measured on different time scales, and governed by different biological processes. In light of this complexity, existing pregnancy risk assessment tools largely focus on predicting a single adverse pregnancy outcome, and make these predictions at some later, post-conception time point.

Methods

We reframe the individual pregnancy attempt as a multistate model comprised of two nested multinomial prediction tasks: one corresponding to conception and the other to the subsequent outcome of that pregnancy. We discuss the estimation of this model in the presence of multiple stages of outcome missingness and then introduce an inverse-probability-weighted Hypervolume Under the Manifold statistic to validate the resulting multivariate risk scores. Finally, we use data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial to illustrate how this multistate competing risks framework might be utilized in practice to construct and validate a preconception pregnancy risk assessment tool.

Results

In the EAGeR study population, the resulting risk profiles are able to meaningfully discriminate between the four pregnancy attempt outcomes of interest and represent a significant improvement over classification by random chance.

Conclusions

As illustrated in our analysis of the EAGeR data, our proposed prediction framework expands the pregnancy risk assessment task in two key ways—by considering a broader array of pregnancy outcomes and by providing the predictions at an earlier, preconception intervention window—providing obstetricians and their patients with more information and opportunities to successfully guide pregnancy attempts.
Estimating risk ratio from any standard epidemiological design by doubling the cases
Authors: Ning Yilin , Lam Anastasia , Reilly Marie
Published: May 2022

Background

Despite the ease of interpretation and communication of a risk ratio (RR), and several other advantages in specific settings, the odds ratio (OR) is more commonly reported in epidemiological and clinical research. This is due to the familiarity of the logistic regression model for estimating adjusted ORs from data gathered in a cross-sectional, cohort or case-control design. The preservation of the OR (but not RR) in case-control samples has contributed to the perception that it is the only valid measure of relative risk from case-control samples. For cohort or cross-sectional data, a method known as ‘doubling-the-cases’ provides valid estimates of RR and an expression for a robust standard error has been derived, but is not available in statistical software packages.

Methods

In this paper, we first describe the doubling-of-cases approach in the cohort setting and then extend its application to case-control studies by incorporating sampling weights and deriving an expression for a robust standard error. The performance of the estimator is evaluated using simulated data, and its application illustrated in a study of neonatal jaundice. We provide an R package that implements the method for any standard design.

Results

Our work illustrates that the doubling-of-cases approach for estimating an adjusted RR from cross-sectional or cohort data can also yield valid RR estimates from case-control data. The approach is straightforward to apply, involving simple modification of the data followed by logistic regression analysis. The method performed well for case-control data from simulated cohorts with a range of prevalence rates. In the application to neonatal jaundice, the RR estimates were similar to those from relative risk regression, whereas the OR from naive logistic regression overestimated the RR despite the low prevalence of the outcome.

Conclusions

By providing an R package that estimates an adjusted RR from cohort, cross-sectional or case-control studies, we have enabled the method to be easily implemented with familiar software, so that investigators are not limited to reporting an OR and can examine the RR when it is of interest.
Prediction models for functional status in community dwelling older adults: a systematic review
Authors: Van Grootven Bastiaan , van Achterberg Theo
Published: May 2022

Background

Disability poses a burden for older persons, and is associated with poor outcomes and high societal costs. Prediction models could potentially identify persons who are at risk for disability. An up to date review of such models is missing.

Objective

To identify models developed for the prediction of functional status in community dwelling older persons.

Methods

A systematic review was performed including studies of older persons that developed and/or validated prediction models for the outcome functional status. Medline and EMBASE were searched, and reference lists and prospective citations were screened for additional references. Risk of bias was assessed using the PROBAST-tool. The performance of models was described and summarized, and the use of predictors was collated using the bag-of-words text mining procedure.

Results

Forty-three studies were included and reported 167 evaluations of prediction models. The median c-statistic values for the multivariable development models ranged between 0.65 and 0.76 (minimum = 0.58, maximum = 0.90), and were consistently higher than the values of the validation models for which median c-statistic values ranged between 0.6 and 0.68 (minimum = 0.50, maximum = 0.81). A total of 559 predictors were used in the models. The five predictors most frequently used were gait speed (n = 47), age (n = 38), cognition (n = 27), frailty (n = 24), and gender (n = 22).

Conclusions

No model can be recommended for implementation in practice. However, frailty models appear to be the most promising, because frailty components (e.g. gait speed) and frailty indexes demonstrated good to excellent predictive performance. However, the risk of study bias was high. Substantial improvements can be made in the methodology.
Key gene network related to primary ciliary dyskinesia in hippocampus of patients with Alzheimer’s disease revealed by weighted gene co-expression network analysis
Authors: Xia Pengcheng , Chen Jing , Bai Xiaohui , Li Ming , Wang Le , Lu Zhiming
Published: May 2022

Background

Alzheimer’s disease (AD) is closely related to aging, showing an increasing incidence rate for years. As one of the main brain regions involved in AD, hippocampus has been extensively studied due to its association with many human diseases. However, little is known about its association with primary ciliary dyskinesia (PCD).

Material and Methods

The microarray data of hippocampus on AD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by weighted gene co-expression network analysis (WGCNA). The gene network modules associated with AD screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network.

Results

Genes involved in PCD were identified in the hippocampus of AD patients. Functional analysis revealed that these genes were mainly enriched in ciliary tissue, ciliary assembly, axoneme assembly, ciliary movement, microtubule based process, microtubule based movement, organelle assembly, axoneme dynamin complex, cell projection tissue, and microtubule cytoskeleton tissue. A total of 20 central genes, e.g.,DYNLRB2, ZMYND10, DRC1, DNAH5, WDR16, TTC25,andARMC4were identified as hub genes related to PCD in hippocampus of AD patients.

Conclusion

Our study demonstrated that AD and PCD have common metabolic pathways. These common pathways provide novel evidence for further investigation of the pathophysiological mechanism and the hub genes suggest new therapeutic targets for the diagnosis and treatment of AD and PCD.

Subjects

Bioinformatics, Cell Biology, Molecular Biology, Neurology.
Cystatin SN promotes epithelial-mesenchymal transition and serves as a prognostic biomarker in lung adenocarcinoma
Authors: Yang Jian , Luo Gaomeng , Li Chang , Zhao Zhunlin , Ju Sheng , Li Qifan , Chen Zhike , Ding Cheng , Tong Xin , Zhao Jun
Published: May 2022

Background

Cystatins are a class of proteins that can inhibit cysteine protease and are widely distributed in human bodily fluids and secretions. Cystatin SN (CST1), a member of the CST superfamily, is abnormally expressed in a variety of tumors. However, its effect on the occurrence and development of lung adenocarcinoma (LUAD) remains unclear.

Methods

We obtained transcriptome analysis data of CST1 from The Cancer Genome Atlas (TCGA) and GSE31210 databases. The association of CST1 expression with prognosis, gene mutations and tumor immune microenvironment was analyzed using public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to investigate the potential mechanisms of CST1.

Results

In this study, we found that CST1 was highly expressed in lung adenocarcinoma and was associated with prognosis and tumor immune microenvironment. Genetic mutations of CST1 were shown to be related to disease-free survival (DFS) by using the c-BioPortal tool. Potential proteins binding to CST1 were identified by constructing a protein-protein interaction (PPI) network. Gene set enrichment analysis (GSEA) of CST1 revealed that CST1 was notably enriched in epithelial-mesenchymal transition (EMT). Cell experiments confirmed that overexpression of CST1 promoted lung adenocarcinoma cells migration and invasion, while knockdown of CST1 significantly inhibited lung adenocarcinoma cells migration and invasion.

Conclusions

Our comprehensive bioinformatics analyses revealed that CST1 may be a novel prognostic biomarker in LUAD. Experiments confirmed that CST1 promotes epithelial-mesenchymal transition in LUAD cells. These findings will help to better understand the distinct role of CST1 in LUAD.
Disparity in prevalence and predictors of undernutrition in children under five among agricultural, pastoral, and agro-pastoral ecological zones of Karamoja sub-region, Uganda: a cross sectional study
Authors: Okidi Lawrence , Ongeng Duncan , Muliro Patrick Simiyu , Matofari Joseph Wafula
Published: May 2022

Background

Undernutrition accounts for nearly half of under-five child mortality in developing countries where household nutrition is largely dependent on agriculture. Despite the strong influence of agroecology on agriculture in those countries, limited information exists on whether undernutrition in children under five varies with agro-ecological location.

Methods

Using Karamoja sub-region of Uganda, one of the most food insecure parts of Eastern Africa as a case area, and applying a multi-stage sampling procedure, and a structured questionnaire, this study examined in a comparative manner, the prevalence and predictors of undernutrition in children under five among the agricultural, pastoral, and agro-pastoral ecological zones. Chi-square test and Kruskal-Wallis test were used to establish the disparity in prevalence of undernutrition and household contextual characteristics, respectively. Binary logistic regression was used to determine the predictors of undernutrition in children under five among the three agro-ecological zones. The level of statistical significance was set at p ≤ 0.05.

Results

The prevalence of underweight, stunting, and wasting ranged from 36 to 58% but varied with agroecology in terms of the peak age ranging from 6 to 37 months. Child characteristics, feeding practices, household economic factors, sanitation factors, and caregiver characteristics that predict undernutrition among children under five were identified (p ≤ 0.05). Caregiver handwashing after using latrine (p = 0.005) and diarrhoea in a fortnight (p < 0.001) increased the likelihood of stunting in pastoral agroecology only whereas cereal storage in both sacks and granary in agro-pastoral zone was associated with reduced likelihood of both underweight (p < 0.001 and p = 0.014) and stunting (p = 0.011 and p = 0.018), respectively. A male child was more likely to be underweight and stunted in pastoral (p = 0.002 and p = 0.011) and agro-pastoral (p = 0.017 and p = 0.002) agroecology, respectively. Household expenses reduced the likelihood of both underweight and wasting in pastoral (p = 0.013 and p = 0.005) and agricultural (p = 0.011 and p = 0.021) agroecology, respectively. Flour storage duration increased the stunting likelihood in pastoral (p = 0.032) and agro-pastoral (p = 0.006) agroecologies.

Conclusion

This study has revealed that, in a food insecure developing country setting such as Karamoja sub-region of Uganda, undernutrition among children under five varies with agroecology. Thus, nutritional interventions in such locations should be agroecology specific.
Cost-effectiveness analysis of hearing screening program for primary school children in southern Iran, Shiraz
Authors: Faramarzi Mohammad , Babakhani fard Sara , Bayati Mohsen , Jafarlou Fatemeh , Parhizgar Mohammadreza , Rezaee Mehdi , Keshavarz Khosro
Published: May 2022

Background

Hearing loss is the second most common chronic disease, the diagnosis and treatment of which can be faster through screening. In addition, early interventions will save significant costs for the education and health systems. Therefore, the present study aimed to evaluate the cost-effectiveness of hearing screening for primary school children in Shiraz.

Methods

This cross-sectional economic evaluation of cost-effectiveness was conducted from the perspective of the health system. The study population comprised all seven-year-old children participating in the screening program in Shiraz. The present study dealt only with direct costs. The expected costs and outcomes, as well as the ICER index were estimated using the decision tree model. The study outcomes included averted disability-adjusted life years (DALY) and true identification of hearing loss cases. The robustness of the results was evaluated using the one-way sensitivity analysis. The TreeAge 2020 and Excel 2016 software were also used to analyze the collected data.

Results

The hearing screening data obtained during 6 years (2015–2020) showed that every year, an average of 22,853 children in Shiraz were examined for hearing, of which 260 were true positive (%1.1). The costs of screening and lack of screening were estimated at $30.32 Purchasing Power Parity (PPP) and $13.75 PPP per child, respectively. The averted DALY due to performing hearing screening was estimated at 7 years for each child. The ICER was positive and equal to $ 0.06 PPP for the identified cases and $ 2.37 PPP per averted DALY. The sensitivity analysis confirmed the robustness of the results.

Conclusions

According to the results, although hearing screening for primary school children had more costs and effectiveness, it was considered cost-effective. Therefore, universal screening with high quality and accuracy is recommended.
Clinical significance of respiratory virus coinfection in children with Mycoplasma pneumoniae pneumonia
Authors: Choo Soojeong , Lee Yun Young , Lee Eun
Published: May 2022

Background

The prevalence of refractory Mycoplasma pneumoniae (MP) pneumonia has been increasing. However, few studies have investigated the impact of respiratory virus coinfection in patients with MP pneumonia, and their results have been inconclusive. This study aimed to investigate the impact of respiratory virus coinfection in children hospitalized with MP pneumonia.

Methods

This study enrolled 145 children hospitalized with MP pneumonia between May 2019 and March 2020. The patients were divided into two groups: the respiratory virus coinfection and non-coinfection groups. All the children underwent polymerase chain reaction testing for respiratory virus infection. Information on clinical, laboratory, and radiologic findings were obtained retrospectively via medical chart reviews.

Results

Children in the respiratory virus coinfection group were younger than those in the non-coinfection group. Respiratory virus coinfection in children hospitalized with MP pneumonia was significantly associated with persistence of fever more than 6 days (adjusted odds ratio [aOR], 2.394; 95% confidence interval [95% CI], 1.172–4.892), severe pneumonia (aOR, 4.602; 95% CI, 1.154–18.353), and poor response to the stepwise approach for MP pneumonia (aOR, 4.354; 95% CI, 1.374–13.800). In addition, higher levels of liver enzymes and lactate dehydrogenase at admission were associated with respiratory virus coinfection in children with MP pneumonia.

Conclusions

The results of this study suggest that respiratory virus coinfection in children hospitalized with MP pneumonia may be associated with refractory MP pneumonia.
Cortical allograft strut augmented with platelet-rich plasma for the treatment of long bone non-union in lower limb- a pilot study
Authors: Wu Shenghui , Quan Kun , Mei Jiong , Dai Min , Song Sa
Published: May 2022

Background

The autogenous iliac bone graft is the first choice of surgical treatment for long bone non-union. However, many factors limit the use of autogenous bone, such as insufficient bone harvest and complications in the donor site. This study aimed to pilot-test the effectiveness of the cortical allograft strut augmented with Platelet-rich plasma (PRP) on long bone non-union in the lower limb.

Method

This study was a one-armed pilot trial, with thirteen men and four women patients scheduled for surgery. Revision surgery for managing long bone non-union included debridement, internal fixation of the cortical allograft strut, and adding PRP in the fracture site. After surgery, outcome measurements of healing rate, healing time, the incidence of revision, and complications, were assessed at least one-year follow-up.

Results

Fourteen of seventeen participants completed all follow-ups. The mean age of 14 patients was 35.9 years (range, 18–56 years), and the mean BMI was 22.44 ± 1.53 kg/m2. All nonunions united after the operation. The mean healing time was 4.6 ± 0.7 months. There was no revision or complication.

Conclusion

Cortical allograft strut augmented with PRP led to healing long bone non-union in the lower limb. More clinical research is required before widespread use.
Perception of online and face to face microbiology laboratory sessions among medical students and faculty at Arabian Gulf University: a mixed method study
Authors: Joji Ronni Mol , Kumar Archana Prabu , Almarabheh Amer , Dar Fazal K , Deifalla Abdel Halim , Tayem Yasin , Ismaeel Abdulrahman Yusuf , Bindayna Khalid , Tabbara Khaled Saeed , Farid Eman , Shadab Mohd , Al Mahmeed Ali , Shahid Mohammad
Published: May 2022

Background

The COVID-19 pandemic has impacted all spheres of society including medical education and healthcare systems. In response to the pandemic, there has been a transition in medical education practice from traditional forms of teaching to online instruction delivery and virtual learning. Effective clinical microbiology education involves a combination of 'hands-on' practical learning and instructional delivery of scientific knowledge. Microbiology practical laboratories are critical learning environments offering 'hands-on' learning experiences that cannot be replicated through online learning. We conducted a mixed-methods study to understand the perception of online and face-to-face microbiology laboratory sessions among the medical students and microbiology faculty at Arabian Gulf University (AGU).

Methods

The study participants were third and fourth-year undergraduate medical students and faculty involved in delivering microbiology labs at AGU. The questionnaire consisted of questions ranging from perceived learning style to attitude towards online delivery of microbiology curriculum. After the questionnaire administration (google form), focus group discussion (FGD) was conducted for students and microbiology faculty separately.

Results

Among 168 students, 50.6% preferred face-to-face lab sessions as compared to 30.4% who preferred online labs, and 51.8% considered online labs to be an essential addition to face-to-face labs. Among the faculty, 85.7% preferred the face-to-face mode of teaching. All the faculty (100%) disagreed that all the microbiology labs teaching should be online. 57.2% considered online labs to be an essential addition to traditional face-to-face labs. Both faculty and students hold that a blended mode of instructional delivery is vital and indispensable for the transfer of skills and knowledge for microbiology students.

Conclusion

The blended mode of delivering microbiology laboratory sessions in medical school is successful and well-received by both students and faculty. Students take the responsibility for furthering their own learning and understanding of concepts. Instructors have also noticed that blending learning strategies also successfully enhances the development of cognitive skills and problem-solving abilities in students. A review of the microbiology lab curriculum is necessary to identify content areas that can be delivered effectively through online, face-to-face lab sessions, or both, supported with appropriate tools and infrastructure.
The H3K27M mutation alters stem cell growth, epigenetic regulation, and differentiation potential
Authors: Kfoury-Beaumont N. , Prakasam R. , Pondugula S. , Lagas J. S. , Matkovich S. , Gontarz P. , Yang L. , Yano H. , Kim A. H. , Rubin J. B. , Kroll K. L.
Published: May 2022

Background

Neurodevelopmental disorders increase brain tumor risk, suggesting that normal brain development may have protective properties. Mutations in epigenetic regulators are common in pediatric brain tumors, highlighting a potentially central role for disrupted epigenetic regulation of normal brain development in tumorigenesis. For example, lysine 27 to methionine mutation (H3K27M) in theH3F3Agene occurs frequently in Diffuse Intrinsic Pontine Gliomas (DIPGs), the most aggressive pediatric glioma. As H3K27M mutation is necessary but insufficient to cause DIPGs, it is accompanied by additional mutations in tumors. However, how H3K27M alone increases vulnerability to DIPG tumorigenesis remains unclear.

Results

Here, we used human embryonic stem cell models with this mutation, in the absence of other DIPG contributory mutations, to investigate how H3K27M alters cellular proliferation and differentiation. We found that H3K27M increased stem cell proliferation and stem cell properties. It interfered with differentiation, promoting anomalous mesodermal and ectodermal gene expression during both multi-lineage and germ layer-specific cell specification, and blocking normal differentiation into neuroectoderm. H3K27M mutant clones exhibited transcriptomic diversity relative to the more homogeneous wildtype population, suggesting reduced fidelity of gene regulation, with aberrant expression of genes involved in stem cell regulation, differentiation, and tumorigenesis. These phenomena were associated with global loss of H3K27me3 and concordant loss of DNA methylation at specific genes in H3K27M-expressing cells.

Conclusions

Together, these data suggest that H3K27M mutation disrupts normal differentiation, maintaining a partially differentiated state with elevated clonogenicity during early development. This disrupted response to early developmental cues could promote tissue properties that enable acquisition of additional mutations that cooperate with H3K27M mutation in genesis of DMG/DIPG. Therefore, this work demonstrates for the first time that H3K27M mutation confers vulnerability to gliomagenesis through persistent clonogenicity and aberrant differentiation and defines associated alterations of histone and DNA methylation.
Gene expression profiles of beta-adrenergic receptors in canine vascular tumors: a preliminary study
Authors: Clanxet Jordi , Teles Mariana , Hernández-Losa Javier , Rueda Manuel Ruiz-Echarri , Benitez-Fusté Luis , Pastor Josep
Published: May 2022

Beta adrenergic receptors (β-AR) play a key role in regulating several hallmark pathways of both benign and malignant human and canine tumors. There is scarce information on the expression of β-AR in canine vascular tumors. Therefore, the purpose of the present research work was to study the mRNA expression levels of the three subtypes of the β-AR genes (ADRB1, ADRB2, ADRB3) in hemangiosarcoma (HSA) and hemangioma (HA), as well as in vascular hamartomas (VH) from dogs.

Fifty samples (n = 50) were obtained from 38 dogs. Twenty-three animals had HSA, eight animals HA and seven animals VH. HSA were auricular (n = 8), splenic (n = 5), cutaneous (n = 6), auricular and splenic (n = 2), cutaneous-muscular (n = 1) and disseminated (n = 1). There were seven cases of HSA that were divided into primary tumor and secondary (metastatic) tumor. Skin and muscle samples with a normal histological study were used as control group. ADRB gene expression was determinate in all samples by real-time quantitative PCR. Results showed that ADRB1, ADRB2 and ADRB3 were overexpressed in HSA when compared to the control group. ADRB2 was overexpressed in HA when compared to the control group. HSA express higher values of ADBR1 (p = 0.0178) compared to VH. There was a high inter-individual variability in the expression of the three subtypes of ADBR. No statistically significant difference in the expression of ADBR genes were observed between HSA primary when compared to metastatic or in different anatomical locations. In conclusion, canine HSA overexpress the three β-AR subtypes and canine HA β2-AR. High variability was observed in β-AR mRNA levels amongst HSA cases.
Exploration of the lower threshold of iodine intake in Southern Chinese young adults based on ‘overflow theory’ in an iodine balance study
Authors: Wang Jun , Zhang Hongmin , Mao Deqian , Tan Hongxing , Yu Wei , Xu Jian , Hong Wenxu , Piao Jianhua , Yang Lichen , Liu Xiaobing , Lu Jiaxi , Li Weidong , Li Yajie , Liu Xiaoli , Yang Xiaoguang
Published: May 2022

Background

Appropriate iodine intake for adults is essential to reduce the prevalence of thyroid diseases, but there is little research data on iodine requirement of Chinese population. This study aimed to explore the iodine requirement of young adults to maintain a healthy status based on ‘overflow theory’.

Methods

Iodine-balance experiment has been performed in this project. We conducted an 18-day study consisted of a 6-day acclimation period and 3 consecutive experimental stages in 37 Chinese healthy young adults (23 female and 14 male). Each stage was consumed for 4 days. Strictly-controlled low-iodine intake diets were provided for adults in the first period, an egg or 125mL milk was added in the second and third period, respectively. The dietary samples, 24-h urine specimens and faeces of volunteers were collected daily for assessment of iodine intake and excretion in volunteers.

Results

Mean values of iodine intake (22.7±3.6, 35.1±3.7, and 52.2±3.8μg/d), excretion (64.7±13.9, 62.3±12.6, and 94.3±14.5μg/d) and iodine balance (-35.2±19.5, -21.0±19.8, and -33.5±26.9μg/d) were significantly different among three periods for male (P<0.001 for all); mean values of iodine intake (16.6±3.1, 29.7±2.7, and 48.0±2.7μg/d), and excretion (47.0±9.9, 55.5±8.1, and 75.7±12.4μg/d) were significantly different among three periods for female (P < 0.001 for all). No significant difference was observed among the 3 periods for female in the iodine balance (-30.5±9.3, -25.9±7.3, and -27.6±12.1μg/d). The linear regression equation of iodine excretion on iodine intake was Y=0.979X+37.04 (male) and Y=0.895X+31.48 (female). Compared with stage 2, iodine excretion increments in stage 3 had exceeded the iodine intake increment for men. The ratio of increment was 1.675 for male when the average iodine intake was 52.2μg/d in stage 3. When the iodine excretion increment equaled to the iodine intake increment, the daily iodine intake of men was 47.0μg.

Conclusion

We have evaluated the iodine requirement of young adults in southern China based on overflow theory. Our results indicate the lower limit of iodine requirement for Chinese young men is 47.0μg/d. The trial was registered at www.chictr.org.cn as ChiCTR1800014877.
Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity
Authors: Loyer Chloé , Lapostolle Arnaud , Urbina Tomas , Elabbadi Alexandre , Lavillegrand Jean-Rémi , Chaigneau Thomas , Simoes Coraly , Dessajan Julien , Desnos Cyrielle , Morin-Brureau Mélanie , Chantran Yannick , Aucouturier Pierre , Guidet Bertrand , Voiriot Guillaume , Ait-Oufella Hafid , Elbim Carole
Published: May 2022

Background

A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome.

Methods

By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2-negative patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity.

Results

At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets—both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide. Moreover patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors.

Conclusions

These data suggest that neutrophil exhaustion may be involved in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome.

Graphic Abstract
Combinatorial assembly and optimisation of designer cellulosomes: a galactomannan case study
Authors: Vanderstraeten Julie , da Fonseca Maria João Maurício , De Groote Philippe , Grimon Dennis , Gerstmans Hans , Kahn Amaranta , Moraïs Sarah , Bayer Edward A. , Briers Yves
Published: May 2022

Background

Designer cellulosomes are self-assembled chimeric enzyme complexes that can be used to improve lignocellulosic biomass degradation. They are composed of a synthetic multimodular backbone protein, termed the scaffoldin, and a range of different chimeric docking enzymes that degrade polysaccharides. Over the years, several functional designer cellulosomes have been constructed. Since many parameters influence the efficiency of these multi-enzyme complexes, there is a need to optimise designer cellulosome architecture by testing combinatorial arrangements of docking enzyme and scaffoldin variants. However, the modular cloning procedures are tedious and cumbersome.

Results

VersaTile is a combinatorial DNA assembly method, allowing the rapid construction and thus comparison of a range of modular proteins. Here, we present the extension of the VersaTile platform to facilitate the construction of designer cellulosomes. We have constructed a tile repository, composed of dockerins, cohesins, linkers, tags and enzymatically active modules. The developed toolbox allows us to efficiently create and optimise designer cellulosomes at an unprecedented speed. As a proof of concept, a trivalent designer cellulosome able to degrade the specific hemicellulose substrate, galactomannan, was constructed and optimised. The main factors influencing cellulosome efficiency were found to be the selected dockerins and linkers and the docking enzyme ratio on the scaffoldin. The optimised designer cellulosome was able to hydrolyse the galactomannan polysaccharide and release mannose and galactose monomers.

Conclusion

We have eliminated one of the main technical hurdles in the designer cellulosome field and anticipate the VersaTile platform to be a starting point in the development of more elaborate multi-enzyme complexes.
Risk factors for the recurrence of relapsing polychondritis
Authors: Yoshida Tsuneyasu , Yoshifuji Hajime , Shirakashi Mirei , Nakakura Akiyoshi , Murakami Kosaku , Kitagori Koji , Akizuki Shuji , Nakashima Ran , Ohmura Koichiro , Morinobu Akio
Published: May 2022

Background

Although the survival rates of patients with relapsing polychondritis (RP) have increased remarkably, the high recurrence rate remains a significant concern for physicians and patients. This retrospective study aimed to investigate the risk factors for RP recurrence.

Methods

Patients with RP who presented to Kyoto University Hospital from January 2000 to March 2020 and fulfilled Damiani’s classification criteria were included. Patients were classified into recurrence and non-recurrence groups. Risk factors for RP recurrence were analysed using a Cox proportional hazards model, and Kaplan–Meier survival curves were drawn.

Results

Thirty-four patients were included. Twenty-five patients (74%) experienced 64 recurrences (mean: 2.56 recurrences per patient). The median duration before the first recurrence was 202 [55−382] days. The median prednisolone dose at the initial recurrence was 10 [5−12.75] mg/day. Tracheal involvement was significantly more frequent in the recurrence group at the initial presentation (44.0% vs. 0.0%, p=0.0172) than in the non-recurrence group, and pre-treatment C-reactive protein levels were significantly higher in the recurrence group than in the non-recurrence group (4.7 vs 1.15 mg/dL, p=0.0024). The Cox proportional hazards model analysis revealed that tracheal involvement (hazard ratio [HR] 4.266 [1.535−13.838], p=0.0048), pre-treatment C-reactive protein level (HR 1.166 [1.040−1.308], p=0.0085), and initial prednisolone monotherapy (HR 4.443 [1.515−16.267], p=0.0056) may be associated with recurrence. The median time before the initial recurrence was significantly longer in patients who received combination therapy with prednisolone and immunosuppressants or biologics (400 vs. 70 days, p=0.0015).

Conclusions

Tracheal involvement, pre-treatment C-reactive protein level, and initial prednisolone monotherapy were risk factors for recurrence in patients with RP. Initial combination therapy with prednisolone and immunosuppressants may delay recurrence.
The effect of lead exposure on IQ test scores in children under 12 years: a systematic review and meta-analysis of case-control studies
Authors: Heidari Serve , Mostafaei Shayan , Razazian Nazanin , Rajati Mojgan , Saeedi Anahita , Rajati Fatemeh
Published: May 2022

An inevitable exposure to the toxic heavy metal such as lead in our environmental can have irreversible effects on children’s mental performance.

In this study, 3316 children in 8 case-control studies were selected for review. The case group was exposed to a concentration of lead above 10 μg/dL, and the control group was exposed to a concentration of less than 10 μg/dL, but the duration of exposure was different among studies, and the subgroup analysis was performed based on this variable.

In the subgroup with duration of exposure less than the average of 4.5 years, the difference of IQ test score between two groups was significant (MD = −3.53) (P-value <0.05). Also, in the subgroup with more than 4.5 years of duration, the difference of IQ test score was significant (MD = −22.63) (P-value < 0.001).

This study demonstrates that the concentration and duration of lead exposure have a large effect on mental function in children.
Evaluation of Electromagnetic Pulse Shielding Performance of Carbon Fiber-Mixed Cement Paste
Authors: Min Tae-Beom , Cho Hyeong-Kyu
Published: May 2022

This study investigated the physical properties and electromagnetic pulse (EMP) shielding performance of cement paste containing small-diameter carbon fibers to develop an EMP-shielding cement. Small-diameter carbon fibers were used as a cement admixture because the powders were approximately 100 μm in length and were visually powder-shaped. As a result of the experiment, it was indicated that ordinary Portland cement do not have shielding performance. However, cement paste with 5% carbon fibers showed effectiveness in compressive strength and EMP shielding. However, the shielding performance did not increase when the cement contained more than 5% carbon fibers. Furthermore, a review of the EMP shielding performance relative to the thickness of the specimen showed that the plain cement without small-diameter carbon fibers did not increase the shielding performance with an increase in thickness, but the shielding performance of the specimens with small-diameter carbon fibers increased with an increase in thickness. Therefore, it was more effective to increase the thickness of the cement containing 5% carbon fibers rather than increasing the carbon fiber content.
Prevalence of malnutrition and associated factors among older adults from urban and rural residences of Metu district, Southwest Ethiopia
Authors: Ferede Yohannes Mulu , Derso Terefe , Sisay Mekonnen
Published: May 2022

Background

In Ethiopia, the proportion of older adults is steadily increasing. This rapidly growing older adult population may increase the burden of malnutrition. However, malnutrition among older adults, particularly those living in rural areas, is regularly underrecognized and/or ignored. There have been no studies among older adults in the Metu district that have used the Min nutritional assessment (MNA). As a result, the purpose of this study is to determine the prevalence of malnutrition and its associated factors among older adults in Metu district, Southwest Ethiopia.

Methods

A community-based comparative cross-sectional study was conducted from May to June 2021 in Metu district. A multi-stage stratified sampling technique was employed. The nutritional status of the older adults was measured by MNA. Data from 616 older adults (308 from urban and 308 from rural residences) was collected through face-to-face interviews using a structured questionnaire. Bivariable and multivariable logistic regression analyses were done to identify factors associated with malnutrition.

Results

According to this study, the overall prevalence of malnutrition in Metu district was 17.5% (95% CI: 14.4%–20.7%). The prevalence of malnutrition in urban and rural residences was 9.9% and 25.2%, respectively. In the overall study, insomnia (AOR: 2.0, 95%CI: 1.1–3.7), residence (AOR: 3.47, 95%CI: 1.8–6.5), and smoking (AOR: 3.7, 95%CI: 2.1–6.7) were associated with malnutrition. In urban residences, depression (AOR: 3.4, 95%CI: 1.2–9.5), dietary diversity score (DDS) (AOR: 3.5, 95%CI: 1.2–10.0), and eating problems (AOR: 2.8, 95%CI: 1.1–7.3) were associated with malnutrition. In rural residence, age (AOR:3.8; 95%CI: 1.2–11), sex (AOR:2.2,95%CI:1.0–4.8), DDS (AOR:5.4,95%CI:2.2–13.3), depression (AOR: 4.6,95%CI:2.2–9.2), and chronic disease (AOR: 3.8 95%CI: 1.8–8.2) were associated with malnutrition.

Conclusions and recommendations

Malnutrition was more prevalent among older adults living in rural areas than in urban areas. In the overall study, insomnia, residence, and smoking were significantly associated with malnutrition. DDS, depression, and eating difficulties were significantly associated with malnutrition among older adults living in urban areas, whereas sex, age, depression, chronic disease, and dietary diversity were factors influencing malnutrition in rural areas. Strengthening strategies aimed at addressing nutrition policy, as well as paying attention to the nutritional needs of the older adult population, can help to improve the health and quality of life of older adults.
The mixed phylogenetic origin of northern pike (Esox lucius Linnaeus 1758) populations in the Middle Danubian drainage
Authors: Takács Péter , Bánó Bálint , Czeglédi István , Erős Tibor , Ferincz Árpád , Gál Blanka , Bánó-Kern Bernadett , Kovács Balázs , Nagy András Attila , Nyeste Krisztián , Lente Vera , Preiszner Bálint , Sipos Sándor , Staszny Ádám , Vitál Zoltán , Weiperth András , Csoma Eszter
Published: May 2022

Background

Pikes, members of genusEsox, are widespread freshwater predators of the northern hemisphere, and important sport fish also. From the Carpathian basin only one species, the northern pike (E. lucius) is noted. At the same time the pike stocks living in this area show high level of phenotypic variance (e.g. various body pattern) and its growth varies highly both among and within populations. These features usually explained by the environmental diversity of the area. Whereas we think that genetic reasons -e.g. the appearance of other/new pike species in the area- may also be responsible for these observed features. Since as no detailed information have been published from the pike populations of this area, so far; we conducted phylogenetic and morphological assay on 88 pike specimens, collected from 49 Middle Danubian sampling sites.

Results

Our phylogenetic surveys showed that the northern pike appear in the study area solely, but all the three of its major lineages (Northern, Circumpolar, Southern) were indicated. Only six specimens represent the Northern lineage, collected from the western part of the study area. The Circumpolar and Southern lineages were common in the Carpathian basin, but the Southern lineage showed higher levels of haplotype diversity than the Circumpolar clade. Which indicates that only the Southern lineage is native in the area, while the other two groups could have appeared in the Middle Danubian system either spontaneously or by human introduction. Moreover, the different clades appeared in the same populations, suggesting the opportunity of inter-lineage hybridisation. From the studied morphologicalal features, the number of scales on the lateral line and the head length showed significant differences among the lineages. At the same time the body pattern of the studied individuals seems to be rather influenced by the ontogenic changes than phylogeny.

Conclusions

The high phenotypic variability of Middle Danubian northern pike populations may be due that all of its three major clades appeared and came in secondary contact in the area. In the within watershed spread of the non-native lineages the human stocking/transfer may play a considerable role.
Traumatic asphyxia in the young: report of two cases and literature review
Authors: Taha Abdulsalam Y.
Published: May 2022

Background

Traumatic asphyxia, also called masque ecchymotique, Ollivier’s syndrome, and Perthes syndrome, is a rare but serious form of chest trauma described for the first time by Ollivier in 1837. The purpose of this study is to report our experience with two cases of traumatic asphyxia and discuss their management in view of the relevant literature.

Results

During a 6-year period, the author treated 2 cases of traumatic (crush) asphyxia in a local teaching hospital. The two patients were males, aged 20 and 30 years and were crushed beneath their vehicles. The presenting symptoms and signs were irritability, dyspnea, cervicofacial cyanosis, petechiae, and sub-conjunctival hemorrhages. The second patient suffered multiple rib fractures, hemopneumothorax, pulmonary contusion, vertebral fracture, and paraplegia. Negative surgical exploration for suspected cardiac tamponade was performed in the first case, while the second was managed conservatively.

The first patient survived whereas the second succumbed because of the associated injuries.

Conclusions

Due to its widespread lesions, traumatic asphyxia should be looked upon as a systemic syndrome. Timely accurate diagnosis and supportive treatment save the majority of patients with traumatic asphyxia. In this rare syndrome, death may result from asphyxia secondary to thoracic compression or from the associated injuries.
Efficacy of indigenous Trichoderma isolates of West Timor, Indonesia, as biocontrol agents of brown spot (Drechslera oryzae) on two upland rice varieties
Authors: Mau Yosep Seran , Prayetno Rikardus Suhendra , Kaka Habil , Naat Kiki Delfiyanti , Henuk Julinda Bendalina Dengga , Hahuly Mayavira Veronica , Widinugraheni Sri , Gandut Yosefina Rovina Yuliaty
Published: May 2022

Background

Brown spot disease is one of the most destructive foliar diseases of rice. Biological control of this disease is considered more environmentally safe, but the biological control agents have limited availability. The fungusTrichodermacan be used as a biocontrol agent for various plant diseases, including brown spots. IndigenousTrichodermaspecies from West Timor were evaluated in this study to reveal their effectiveness in reducing brown spot disease of upland rice. The study was conducted under a screen house condition using a factorial treatment design laid out in a completely randomized design. The two factors were the brown spot disease control method (T. viride, T. harzianum, T. hamatum, fungicide Trivia 73 WP, and a control treatment) and upland rice genotype (Inpago 7 and Breun Senaren 2).

Results

The results showed thatTrichodermaspp. and the fungicide Trivia 73 WP caused significantly lower AUDPC and apparent infection rate than the control treatment. The total phenol content and agronomic characters (number of reproductive tillers per plant, number of filled grains per panicle, grain yield per plant) were higher in theTrichodermaand fungicide treatments than the control treatment. Meanwhile, tannin and saponin levels were non-significantly different among treatments.Trichodermaand the fungicide Trivia treatments effectively suppressed brown spot disease of upland rice, and the efficacy was dependent on the rice variety, with a mean efficacy range over the two varieties of 27.05–36.42%. TheTrichodermaand the fungicide Trivia treatments increased the grain yield per plant differentially in the 2 rice varieties, with a mean grain yield increase over the 2 varieties of 13.0% (T. viride), 23.5% (T. harzianum), 35.0% (T. hamatum), and 19.9%(Trivia 73 WP).

Conclusion

Efficacy of localTrichodermaof West Timor and the fungicide Trivia treatments were varietal dependent withT. hamatumbeing the most effective in reducing the brown spot disease and producing the highest grain yield increase over the 2 rice varieties. The localTrichodermaspecies of West Timor have a future potential as biocontrol agents of upland rice brown spot disease, but it is necessary to further evaluate their effectiveness against the disease in replicated field trials.