bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and external causes of traumatic brain injury and spinal cord injury mortality in south China, 2014–2018: an ecological study
Authors: Zheng Xue-yan , Yi Qian , Xu Xiao-jun , Meng Rui-lin , Ma Shu-li , Tang Si-li , Xu Hao-feng , Xu Ying-shan , Xu Yan-jun , Yang Yi
Published: December 2021

Background

The epidemiological evidence of traumatic brain injury (TBI) and spinal cord injury (SCI) mortality in mainland China is lacking. We aimed to assess the trends of TBI and SCI mortality, and their association with sex, age, location and external causes of injury in south China.

Methods

Mortality data were derived from the Disease Surveillance Points (DSPs) system of Guangdong province between 2014 and 2018. We examined the trends in mortality with Cochran–Armitage trend test, and the association between the socio-demographic factors and the TBI and SCI mortality by using negative binomial models. Subgroup analysis was performed by stratifying the external causes of TBI and SCI.

Results

The age-standardized TBI mortality remained relatively stable (from 11.6 to 15.4 per 100,000), while the SCI mortality increased by 148.3% from 2014 to 2018. Compared with females and urban residents, the adjusted mortality rate ratios of males and rural residents were 2.3 and 2.0 for TBI, and 2.2 and 4.6 for SCI, respectively. TBI and SCI mortality increased substantially with age. Motor vehicle crashes and falls were the leading causes of TBI mortality in residents aged under 75 years and over 75 years, respectively. Falls were the most important external cause for SCI death of all ages.

Conclusions

Being male, rural and elderly residents are at higher risk of dying from TBI and SCI. The substantial burden of TBI and SCI caused by road traffic crashes and falls has called for the urgent need to improve injury prevention, pre-hospital aid, hospital treatment and recovery.
Long-term trends in blood pressure and hypertension in Russia: an analysis of data from 14 health surveys conducted in 1975–2017
Authors: Churilova Elena , Shkolnikov Vladimir M. , Shalnova Svetlana A. , Kudryavtsev Alexander V. , Malyutina Sofia , Nilssen Odd , Laatikainen Tiina , Leon David A.
Published: December 2021

Background

Hypertension is recognized as an important contributor to high cardiovascular mortality in Russia. A comprehensive analysis of data from Russian studies that measured blood pressure in population-based samples has not been previously undertaken. This study aims to identify trends and patterns in mean blood pressure and the prevalence of hypertension in Russia over the most recent 40 years.

Methods

We obtained anonymized individual records of blood pressure measurements from 14 surveys conducted in Russia in 1975–2017 relating to a total of 137,687 individuals. For comparative purposes we obtained equivalent data from 4 surveys in the USA and England for 23,864 individuals. A meta-regression on aggregated data adjusted for education was undertaken to estimate time trends in mean systolic and diastolic blood pressure, the prevalence of elevated blood pressure (> 140/90 mmHg), and hypertension (defined as elevated blood pressure and/or the use of blood pressure-lowering) medication. A meta-analysis of pooled individual-level data was used to assess male-female differences in blood pressure and hypertension.

Results

During the period 1975–2017 mean blood pressure, the prevalence of elevated blood pressure and hypertension remained stable among Russian men. Among Russian women, mean systolic blood pressure decreased at an annual rate of 0.25 mmHg (p < 0.1) at age 35–54 years and by 0.8 mmHg (p < 0.01) at ages 55 and over. The prevalence of elevated blood pressure also decreased by 0.8% per year (p < 0.01), but the prevalence of hypertension remained stable. Mean blood pressure and prevalence of hypertension were higher in Russia compared to the USA and England at all ages and for both sexes.

Conclusions

In contrast to the generally observed downward trend in elevated blood pressure in many other countries, levels in Russia have changed little over the past 40 years, although there are some positive trends among women. Improved strategies to bring down the high levels of mean blood pressure and hypertension in Russia compared to countries such as England and the USA are important to further reduce the high burden of CVD in Russia.
Integrative analysis of lung molecular signatures reveals key drivers of idiopathic pulmonary fibrosis
Authors: Kim Sung Kyoung , Jung Seung Min , Park Kyung-Su , Kim Ki-Jo
Published: December 2021

Background

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a high clinical burden. The molecular signatures of IPF were analyzed to distinguish molecular subgroups and identify key driver genes and therapeutic targets.

Methods

Thirteen datasets of lung tissue transcriptomics including 585 IPF patients and 362 normal controls were obtained from the databases and subjected to filtration of differentially expressed genes (DEGs). A functional enrichment analysis, agglomerative hierarchical clustering, network-based key driver analysis, and diffusion scoring were performed, and the association of enriched pathways and clinical parameters was evaluated.

Results

A total of 2,967 upregulated DEGs was filtered during the comparison of gene expression profiles of lung tissues between IPF patients and healthy controls. The core molecular network of IPF featured p53 signaling pathway and cellular senescence. IPF patients were classified into two molecular subgroups (C1, C2) via unsupervised clustering. C1 was more enriched in the p53 signaling pathway and ciliated cells and presented a worse prognostic score, while C2 was more enriched for cellular senescence, profibrosing pathways, and alveolar epithelial cells. The p53 signaling pathway was closely correlated with a decline in forced vital capacity and carbon monoxide diffusion capacity and with the activation of cellular senescence. CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators as evidence by high diffusion scores in the disease module. Currently available and investigational drugs showed differential diffusion scores in terms of their target molecules.

Conclusions

An integrative molecular analysis of IPF lungs identified two molecular subgroups with distinct pathobiological characteristics and clinical prognostic scores. Inhibition against CDKs or HDACs showed great promise for controlling lung fibrosis. This approach provided molecular insights to support the prediction of clinical outcomes and the selection of therapeutic targets in IPF patients.
Low serum calcium is associated with perioperative blood loss and transfusion rate in elderly patients with hip fracture: a retrospective study
Authors: Wang Zhicong , Chen Xi , Chen Yan , Yang Ling , Wang Hong , Jiang Wei , Liu Shuping , Liu Yuehong
Published: December 2021

Background

To investigate whether hypocalcemia influenced total blood loss and transfusion rate in elderly patients with hip fracture.

Methods

From our hip fracture database, patients were consecutively included between January 2014 and December 2020. Serum calcium level was corrected for albumin concentration, and hypocalcaemia was defined as corrected calcium < 2.11 mmol/L. Hemoglobin and hematocrit were obtained on admission day and postoperative day, and blood transfusions were collected. According to the combination formulas of Nadler and Gross, the total blood loss of each patient was calculated. Risk factors were further analyzed by multivariate linear regression.

Results

A total of 583 consecutive elderly hip fracture patients were finally included (mean age 79.32 ± 8.18 years, 68.61% female). On admission, the mean serum corrected calcium level was 2.17 ± 0.14 mmol/L, and the prevalence of hypocalcemia was 33.11% (95%CI: 29.42–37.02). When comparing patients with normal calcium, hypocalcemia patients exhibited a higher blood transfusion rate (7.69% vs 16.06%,P < 0.05), and significantly larger total blood loss (607.86 ± 497.07 ml vs 719.18 ± 569.98 ml,P < 0.05). Multivariate linear regression analysis showed that male, anemia on admission, time from injury to hospital, intertrochanteric fracture, blood transfusion and hypocalcemia were independently associated with increased total blood loss (P < 0.05).

Conclusion

Hypocalcemia is common in elderly patients with hip fracture, and significantly associated with more total blood loss and blood transfusion. The other risk factors for increased total blood loss are male, anemia on admission, time from injury to hospital, intertrochanteric fracture, and blood transfusion.

Level of evidence

Level III, retrospective study.
Risk of coronary heart disease in patients with periodontitis among the middled-aged and elderly in China: a cohort study
Authors: Gao Kaikai , Wu Zhiyuan , Liu Yue , Tao Lixin , Luo Yanxia , Yang Xinghua , Zhang Jingbo , Guo Xiuhua , Wang Songlin
Published: December 2021

Background

Convincing evidence of the periodontitis as a risk factor for coronary heart disease (CHD) is lacking due to shared risk factors, and no cohort study has investigated the association between CHD and periodontitis in Chinese populations.

Methods

This study used a prospective cohort study design. The analysis included 4591 participants aged 40 years and older (3146 men and 1445 women). The association between CHD and periodontitis was estimated using relative risk (RR) calculated using modified Poisson regression. Multiple mediation analysis was used to differentiate the relative effects (RE) from different risk factors on the effect of periodontitis on CHD.

Results

In the analysis using the imputed dataset and fully adjusted model, participants with periodontitis at baseline had 37% increased risk of CHD overall compared to those without periodontitis at baseline (RR 1.37; 95% CI 0.96–1.95). Most of the association can be explained by age, sex, history of diabetes, history of hypertension, uric acid and education (RE 0.76; 95% CI 0.41–1.02).

Conclusion

Periodontitis was weakly associated with an increased risk of CHD among the middled-aged and elderly in China. Further studies are required to identify more mediators and elucidate the mechanisms of how periodontitis increases the risk of CHD.
Oral disease burden of dentate older adults living in long-term care facilities: FINORAL study
Authors: Julkunen Lina , Hiltunen Kaija , Kautiainen Hannu , Saarela Riitta K. T. , Pitkälä Kaisu H. , Mäntylä Päivi
Published: December 2021

Background

A growing number of older adults have natural teeth and are at high risk of oral diseases, which are induced by oral bacterial accumulation and proceed unnoticed and quietly. Our aim was (1) to examine the association of oral disease burden (ODB) with health and functioning among dentate long-term care residents, and (2) to find easily detectable signs for nurses to identify residents’ poor oral health.

Methods

In this cross-sectional observational study dentists examined 209 residents’ oral status, and nurses assessed residents for their functioning and nutrition in long-term care facilities in Helsinki, Finland. ODB was defined by asymptotic dental score (ADS). Six clinical signs of residents’ poor oral health were considered as potentially easy for nurses to detect: lesions on lips, teeth with increased mobility, lesions on oral mucosa, eating soft or pureed food, unclear speech, and needing assistance in eating. The association of these was tested with high ODB as outcome.

Results

Participants were grouped according to their ADS scores: low (n = 39), moderate (n = 96) and high ODB (n = 74). ODB was linearly associated with coronary artery disease and poor cognitive and physical functioning: needing assistance in eating, poor ability to make contact, and unclear speech but not with other diseases including dementia or demographic characteristics. Furthermore, ODB was linearly associated with eating soft or pureed food. Of the six selected, easily detectable signs, having at least two positive signs gave 89% sensitivity to detecting high ODB.

Conclusion

Poor oral health was common and ODB accumulated among residents with poor functioning. Nurses may use a few easily detectable signs to screen residents’ oral health when considering a resident’s need for consultation with an oral health professional.
Improved accuracy of digital implant impressions with newly designed scan bodies: an in vivo evaluation in beagle dogs
Authors: Huang Ruoxuan , Liu Yuanxiang , Huang Baoxin , Zhou Fengxing , Chen Zhuofan , Li Zhipeng
Published: December 2021

Background

The accuracy of digital impressions for fully edentulous cases is currently insufficient for routinely clinical application. To overcome the challenge, a modified scan body was introduced, which demonstrated satisfactory accuracy in vitro. The aim of this study was to evaluate the accuracy of digital impressions using the modified scan bodies with extensional structure versus scan bodies without extensional structure in mandible with two implants in beagle dogs.

Methods

The unilateral mandibular second premolar to second molar were extracted in four beagle dogs. Twelve weeks later, two implants were placed. Five repeated digital impressions were performed with an intraoral scanner on each dog using each of the two different scan bodies: Group I—scan body without extensional structure (SB); Group II—scan body with extensional structure (SBE). The scans were exported to Standard Tessellation Language (STL) files to serve as test data. The dogs were sacrificed and the dissected mandibles were digitalized with a lab scanner to provide reference data. Linear and angular deviations were calculated in an inspection software for accuracy assessment. Statistical analysis was performed with two-way ANOVA. The level of significance was set at α = 0.05.

Results

For trueness assessment, the mean of absolute linear/angular deviations were 119.53 μm/0.75 degrees in Group I and 68.89 μm/0.36 degrees in Group II. SBE was more accurate than SB regarding both linear (p = 0.008) and angular (p = 0.049) deviations. For precision assessment, the mean of absolute linear/angular deviations were 63.01 μm/0.47 degrees in Group I and 38.38 μm/0.24 degrees in Group II. No significant difference was found.

Conclusions

The application of SBE significantly improved the trueness of digital impressions in mandible with two implants compared to SB. No significant difference was found in terms of precision.
Negative histology in cervical specimens obtained with the "see and treat" method among women at a referral center in Rio de Janeiro, Brazil: a cross-sectional study
Authors: Teodoro Renata Pereira , Scherer Danielle , de Camargo Maria José , da Costa Ana Carolina Carioca , de Andrade Cecília Vianna , Russomano Fábio
Published: December 2021

Background

According to the Brazilian Guidelines on Cervical Cancer Screening, women with cytopathologic diagnosis of high-grade intraepithelial lesion, abnormal colposcopic findings, fully visible squamocolumnar junction and age 25 years or older should be treated at the first visit (“see and treat—S&T”). The main limitation to this approach is the risk of overtreatment, identified by histology without preinvasive lesion. The objectives of this study were to identify the overtreatment rate in women undergoing S&T in cervical cancer prevention at a referral center with extensive experience with the method and to detect possible factors associated with this rate.

Methods

This was a cross-sectional study that analyzed records from a database with 616 women submitted to S&T from 1996 to 2017. Negative histology was defined as the following histopathologic results: human papillomavirus without cervical intraepithelial neoplasia (CIN), inflammatory, low-grade squamous intraepithelial lesion, and CIN 1.

Results

Of the 616 women, there were 52 (8.44%, 95%CI 6.25–10.64%) with a histopathologic report without preinvasive cervical lesion. No statistical association was found between this outcome and age or a significant downward trend over time.

Conclusion

The overtreatment rate in this study can be considered low and consistent with the acceptable rates reported in the literature, reinforcing the prevailing Brazilian guideline, in which the benefits of immediate treatment outweigh the risk of losses following biopsy.
Weighted Cox regression for the prediction of heterogeneous patient subgroups
Authors: Madjar Katrin , Rahnenführer Jörg
Published: December 2021

Background

An important task in clinical medicine is the construction of risk prediction models for specific subgroups of patients based on high-dimensional molecular measurements such as gene expression data. Major objectives in modeling high-dimensional data are good prediction performance and feature selection to find a subset of predictors that are truly associated with a clinical outcome such as a time-to-event endpoint. In clinical practice, this task is challenging since patient cohorts are typically small and can be heterogeneous with regard to their relationship between predictors and outcome. When data of several subgroups of patients with the same or similar disease are available, it is tempting to combine them to increase sample size, such as in multicenter studies. However, heterogeneity between subgroups can lead to biased results and subgroup-specific effects may remain undetected.

Methods

For this situation, we propose a penalized Cox regression model with a weighted version of the Cox partial likelihood that includes patients of all subgroups but assigns them individual weights based on their subgroup affiliation. The weights are estimated from the data such that patients who are likely to belong to the subgroup of interest obtain higher weights in the subgroup-specific model.

Results

Our proposed approach is evaluated through simulations and application to real lung cancer cohorts, and compared to existing approaches. Simulation results demonstrate that our proposed model is superior to standard approaches in terms of prediction performance and variable selection accuracy when the sample size is small.

Conclusions

The results suggest that sharing information between subgroups by incorporating appropriate weights into the likelihood can increase power to identify the prognostic covariates and improve risk prediction.
Modelling and identification of characteristic kinematic features preceding freezing of gait with convolutional neural networks and layer-wise relevance propagation
Authors: Filtjens Benjamin , Ginis Pieter , Nieuwboer Alice , Afzal Muhammad Raheel , Spildooren Joke , Vanrumste Bart , Slaets Peter
Published: December 2021

Background

Although deep neural networks (DNNs) are showing state of the art performance in clinical gait analysis, they are considered to be black-box algorithms. In other words, there is a lack of direct understanding of a DNN’s ability to identify relevant features, hindering clinical acceptance. Interpretability methods have been developed to ameliorate this concern by providing a way to explain DNN predictions.

Methods

This paper proposes the use of an interpretability method to explain DNN decisions for classifying the movement that precedes freezing of gait (FOG), one of the most debilitating symptoms of Parkinson’s disease (PD). The proposed two-stage pipeline consists of (1) a convolutional neural network (CNN) to model the reduction of movement present before a FOG episode, and (2) layer-wise relevance propagation (LRP) to visualize the underlying features that the CNN perceives as important to model the pathology. The CNN was trained with the sagittal plane kinematics from a motion capture dataset of fourteen PD patients with FOG. The robustness of the model predictions and learned features was further assessed on fourteen PD patients without FOG and fourteen age-matched healthy controls.

Results

The CNN proved highly accurate in modelling the movement that precedes FOG, with 86.8% of the strides being correctly identified. However, the CNN model was unable to model the movement for one of the seven patients that froze during the protocol. The LRP interpretability case study shows that (1) the kinematic features perceived as most relevant by the CNN are the reduced peak knee flexion and the fixed ankle dorsiflexion during the swing phase, (2) very little relevance for FOG is observed in the PD patients without FOG and the healthy control subjects, and (3) the poor predictive performance of one subject is attributed to the patient’s unique and severely flexed gait signature.

Conclusions

The proposed pipeline can aid clinicians in explaining DNN decisions in clinical gait analysis and aid machine learning practitioners in assessing the generalization of their models by ensuring that the predictions are based on meaningful kinematic features.
Including undocumented migrants in universal health coverage: a maternal health case study from the Thailand-Myanmar border
Authors: Tschirhart Naomi , Jiraporncharoen Wichuda , Thongkhamcharoen Rojanasak , Yoonut Kulyapa , Ottersen Trygve , Angkurawaranon Chaisiri
Published: December 2021

Background

Many countries aspiring to achieve universal health coverage struggle with how to ensure health coverage for undocumented migrants. Using a case study of maternal health care in a Thailand-Myanmar border region this article explores coverage for migrants, service provision challenges and the contribution of a voluntary health insurance program.

Methods

In 2018 we interviewed 18 key informants who provided, oversaw or contributed to maternal healthcare services for migrant women in the border region of Tak province, Thailand.

Results

In this region, we found that public and non-profit providers helped increase healthcare coverage beyond undocumented migrants’ official entitlements. Interview participants explained that Free and low-cost antenatal care (ANC) is provided to undocumented migrants through migrant specific clinics, outreach programs and health posts. Hospitals offer emergency birth care, although uninsured migrant patients are subsequently billed for the services. Care providers identified sustainability, institutional debt from unpaid obstetric hospital bills, cross border logistical difficulties and the late arrival of patients requiring emergency lifesaving interventions as challenges when providing care to undocumented migrants. An insurance fund was developed to provide coverage for costly emergency interventions at Thai government hospitals. The insurance fund, along with existing free and low-cost services, helped increase population coverage, range of services and financial protection for undocumented migrants.

Conclusions

This case study offers considerations for extending health coverage to undocumented populations. Non-profit insurance funds can help to improve healthcare entitlements, provide financial protection and reduce service providers’ debt. However, there are limits to programs that offer voluntary coverage for undocumented migrants. High costs associated with emergency interventions along with gaps in insurance coverage challenge the sustainability for NGO, non-profit and government health providers and may be financially disastrous for patients. Finally, in international border regions with high mobility, it may be valuable to implement and strengthen cross border referrals and health insurance for migrants.
Airway IL-1β associates with IL-5 production following dust mite allergen inhalation in humans
Authors: Burbank Allison J. , Schworer Stephen A. , Sood Amika , Almond Martha , Chason Kelly , Bean Nathan , Zhou Haibo , Hernandez Michelle L.
Published: December 2021

Background

Preclinical studies implicate interleukin (IL)-1β as a key mediator of asthma and have shown the efficacy of IL-1 antagonism for treatment of allergic airway inflammation; human studies in this area are lacking.

Objectives

Our aim was to study the relationship of airway IL-1β to features of acute allergen-induced asthma exacerbation in humans.

Methods

Dust mite-allergic adults with mild asthma underwent inhalation challenge withDermatophagoides farinae. Fractional exhaled nitric oxide (FeNO), induced sputum and peripheral blood samples were obtained pre- and 24 h post-challenge. Spirometry was performed before and throughout the challenge at 10-min intervals, and allergen responsiveness was defined by a 20% fall in Forced Expiratory Volume in 1 s (FEV1). Sputum samples were analyzed for inflammatory cells, cytokines and chemokines. Multiple linear regression was employed to test the association between sputum IL-1β concentration and biomarkers of T helper type 2 (T2)-dominant inflammation.

Results

Fourteen volunteers underwent inhaled allergen challenge. Allergen responsive volunteers showed a greater positive change in IL-1β in sputum following allergen challenge compared to non-responders. Higher pre-challenge sputum IL-1β was associated with greater increase in sputum IL-5 (p = 0.004), sputum eosinophils (p = 0.001) and blood IL-5 (p = 0.003) following allergen challenge. Allergen-induced sputum IL-1β production was significantly associated with sputum and blood IL-5 (p < 0.001 and p = 0.007, respectively), sputum IL-4 (p = 0.001), IL-13 (p = 0.026), eosinophils (p = 0.008) and FeNO (p = 0.03).

Conclusions

The positive association between production of IL-1β and biomarkers of T2 inflammation, particularly IL-5, in humans is consistent with work in animal models that demonstrates a link between IL-1β and the pathophysiology of allergic asthma. The role of IL-1β in human asthma warrants further study.
Oleaginous yeasts- substrate preference and lipid productivity: a view on the performance of microbial lipid producers
Authors: Shaigani Pariya , Awad Dania , Redai Veronika , Fuchs Monika , Haack Martina , Mehlmer Norbert , Brueck Thomas
Published: December 2021

Background

Oleaginous yeasts are promising microbial platforms for sustainable, bio-based production of biofuels and oleochemical building blocks. Bio-based residues provide sustainable and cost-effective carbon sources for fermentative yeast oil production without land-use change. Considering the regional abundancy of different waste streams, we chose complex biomass residue streams of marine origin; macroalgae hydrolysate, and terrestrial origin; wheat straw hydrolysate in the presence, and absence of corn steep liquor as a complex nitrogen source. We investigated the biomass and lipid yields of an array of well-described oleaginous yeasts; R. glutinis, T. asahii, R. mucilaginosa, R. toruloides, C. oleaginosus growing on these hydrolysates. Furthermore, their sugar utilization, fatty acid profile, and inhibitory effect of the hydrolysates on yeast growth were compared. For correlative reference, we initially performed comparative growth experiments for the strains on individual monomeric sugars separately. Each of these monomeric sugars was a dominant carbon source in the complex biomass hydrolysates evaluated in this study. In addition, we evaluated N-acetylglucosamine, the monomeric building block of chitin, as a low-cost nitrogen and carbon source in yeast fermentation.

Results

C. oleaginosus provided the highest biomass and lipid yields. In the wheat straw and brown algae hydrolysates, this yeast strain gained 7.5 g/L and 3.8 g/L lipids, respectively. Cultivation in algae hydrolysate resulted in a higher level of unsaturated fatty acids in the lipids accumulated by all yeast strains. R. toruloides and C. oleaginosus were able to effectively co-utilize mannitol, glucose, and xylose. Growth rates on wheat straw hydrolysate were enhanced in presence of corn steep liquor.

Conclusions

Among the yeast strains investigated in this study, C. oleaginosus proved to be the most versatile strain in terms of substrate utilization, productivity, and tolerance in the complex media. Various fatty acid profiles obtained on each substrate encourage the manipulation of culture conditions to achieve the desired fatty acid composition for each application. This could be accomplished by combining the element of carbon source with other formerly studied factors such as temperature and oxygen. Moreover, corn steep liquor showed promise for enhancement of growth in the oleaginous strains provided that carbon substrate is available.
The history, state of the art and future prospects for oleaginous yeast research
Authors: Abeln Felix , Chuck Christopher J.
Published: December 2021

Lipid-based biofuels, such as biodiesel and hydroprocessed esters, are a central part of the global initiative to reduce the environmental impact of the transport sector. The vast majority of production is currently from first-generation feedstocks, such as rapeseed oil, and waste cooking oils. However, the increased exploitation of soybean oil and palm oil has led to vast deforestation, smog emissions and heavily impacted on biodiversity in tropical regions. One promising alternative, potentially capable of meeting future demand sustainably, are oleaginous yeasts. Despite being known about for 143 years, there has been an increasing effort in the last decade to develop a viable industrial system, with currently around 100 research papers published annually. In the academic literature, approximately 160 native yeasts have been reported to produce over 20% of their dry weight in a glyceride-rich oil. The most intensively studied oleaginous yeast have beenCutaneotrichosporon oleaginosus(20% of publications),Rhodotorula toruloides(19%) andYarrowia lipolytica(19%). Oleaginous yeasts have been primarily grown on single saccharides (60%), hydrolysates (26%) or glycerol (19%), and mainly on the mL scale (66%). Process development and genetic modification (7%) have been applied to alter yeast performance and the lipids, towards the production of biofuels (77%), food/supplements (24%), oleochemicals (19%) or animal feed (3%). Despite over a century of research and the recent application of advanced genetic engineering techniques, the industrial production of an economically viable commodity oil substitute remains elusive. This is mainly due to the estimated high production cost, however, over the course of the twenty-first century where climate change will drastically change global food supply networks and direct governmental action will likely be levied at more destructive crops, yeast lipids offer a flexible platform for localised, sustainable lipid production. Based on data from the large majority of oleaginous yeast academic publications, this review is a guide through the history of oleaginous yeast research, an assessment of the best growth and lipid production achieved to date, the various strategies employed towards industrial production and importantly, a critical discussion about what needs to be built on this huge body of work to make producing a yeast-derived, more sustainable, glyceride oil a commercial reality.
MiR-155-5p suppresses SOX1 to promote proliferation of cholangiocarcinoma via RAF/MEK/ERK pathway
Authors: Wang Da , Xiong Fei , Wu Guanhua , Liu Wenzheng , Wang Bing , Chen Yongjun
Published: December 2021

Background

Accumulating evidence has demonstrated the close relation of SOX1 with tumorigenesis and tumor progression. Upregulation of SOX1 was recently shown to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) is not well characterized.

Methods

Expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined using public GEO database. Western blot and immunohistochemistry were used to confirm the expression levels. Cell proliferation assay (CCK-8) and colony formation assay were performed to assess proliferation of CCA cells. A mouse model of subcutaneous transplantable tumors was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were determined using Targetscan and dual-luciferase reporter assay.

Results

SOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and suppressed tumor growth in vivo. miR-155-5p directly targeted the 3′-untranslated region (3′UTR) of SOX1 and inhibited expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation, and thus CCA proliferation. However, restoration of SOX1 expression in miR-155-5p overexpressing cell lines decreased the phosphorylation level of RAF, MEK and ERK, as well as the proliferation of CCA cells.

Conclusion

MiR-155-5p decreased the expression of SOX1 by binding to its 3′UTR, which activated the RAF/MEK/ERK signaling pathway and promoted CCA progression.
Femtomolar and locus-specific detection of N6-methyladenine in DNA by integrating double-hindered replication and nucleic acid-functionalized MB@Zr-MOF
Authors: Zheng Qingyuan , Wang Tong , Li Xinmin , Qian Husun , Bian Xintong , Li Xingrong , Bai Huijie , Ding Shijia , Yan Yurong
Published: December 2021

In this study, a novel electrochemical biosensor was constructed for ultrasensitive and locus-specific detection of N6-Methyladenine (m6A) in DNA using double-hindered replication and nucleic acid-coated methylene blue (MB)@Zr-MOF. Based on the combination of m6A-impeded replication and AgI-mediated mismatch replication, this mode could effectively stop the extension of the strand once DNA polymerase encountered m6A site, which specifically distinguish the m6A site from natural A site in DNA. Also, Zr-MOF with high porosity and negative surface potential features was carefully chose to load cationic MB, resulting a stable and robust MB@Zr-MOF electrochemical tag. As a result, the developed biosensor exhibited a wide linear range from 1 fM to 1 nM with detection limit down to 0.89 fM. Profiting from the high sensitivity and selectivity, the biosensing strategy revealed good applicability, which had been demonstrated by quantitating m6A DNA at specific site in biological matrix. Thus, the biosensor provides a promising platform for locus-specific m6A DNA analysis.

Graphical Abstract
Delineation of colorectal cancer ligand-receptor interactions and their roles in the tumor microenvironment and prognosis
Authors: Lin Hexin , Xia Lu , Lian Jiabian , Chen Yinan , Zhang Yiyi , Zhuang Zhicheng , Cai HuaJun , You Jun , Guan Guoxian
Published: December 2021

Background

Immunotherapies targeting ligand-receptor interactions (LRIs) are advancing rapidly in the treatment of colorectal cancer (CRC), and LRIs also affect many aspects of CRC development. However, the pattern of LRIs in CRC and their effect on tumor microenvironment and clinical value are still unclear.

Methods

We delineated the pattern of LRIs in 55,539 single-cell RNA sequencing (scRNA-seq) samples from 29 patients with CRC and three bulk RNA-seq datasets containing data from 1411 CRC patients. Then the influence of tumor microenvironment, immunotherapy and prognosis of CRC patients were comprehensively investigated.

Results

We calculated the strength of 1893 ligand-receptor pairs between 25 cell types to reconstruct the spatial structure of CRC. We identified tumor subtypes based on LRIs, revealed the relationship between the subtypes and immunotherapy efficacy and explored the ligand-receptor pairs and specific targets affecting the abundance of tumor-infiltrating lymphocytes. Finally, a prognostic model based on ligand-receptor pairs was constructed and validated.

Conclusion

Overall, through the comprehensive and in-depth investigation of the existing ligand-receptor pairs, this study provides new ideas for CRC subtype classification, a new risk screening tool for CRC patients, and potential ligand-receptor pair targets and pathways for CRC therapy.
Serum metabolomic and lipidomic profiling identifies diagnostic biomarkers for seropositive and seronegative rheumatoid arthritis patients
Authors: Luan Hemi , Gu Wanjian , Li Hua , Wang Zi , Lu Lu , Ke Mengying , Lu Jiawei , Chen Wenjun , Lan Zhangzhang , Xiao Yanlin , Xu Jinyue , Zhang Yi , Cai Zongwei , Liu Shijia , Zhang Wenyong
Published: December 2021

Background

Diagnosing seronegative rheumatoid arthritis (RA) can be challenging due to complex diagnostic criteria. We sought to discover diagnostic biomarkers for seronegative RA cases by studying metabolomic and lipidomic changes in RA patient serum.

Methods

We performed comprehensive metabolomic and lipidomic profiling in serum of 225 RA patients and 100 normal controls. These samples were divided into a discovery set (n = 243) and a validation set (n = 82). A machine-learning-based multivariate classification model was constructed using distinctive metabolites and lipids signals.

Results

Twenty-six metabolites and lipids were identified from the discovery cohort to construct a RA diagnosis model. The model was subsequently tested on a validation set and achieved accuracy of 90.2%, with sensitivity of 89.7% and specificity of 90.6%. Both seropositive and seronegative patients were identified using this model. A co-occurrence network using serum omics profiles was built and parsed into six modules, showing significant association between the inflammation and immune activity markers and aberrant metabolism of energy metabolism, lipids metabolism and amino acid metabolism. Acyl carnitines (20:3), aspartyl-phenylalanine, pipecolic acid, phosphatidylethanolamine PE (18:1) and lysophosphatidylethanolamine LPE (20:3) were positively correlated with the RA disease activity, while histidine and phosphatidic acid PA (28:0) were negatively correlated with the RA disease activity.

Conclusions

A panel of 26 serum markers were selected from omics profiles to build a machine-learning-based prediction model that could aid in diagnosing seronegative RA patients. Potential markers were also identified in stratifying RA cases based on disease activity.
Renal function in Japanese HIV-1-positive patients who switch to tenofovir alafenamide fumarate after long-term tenofovir disoproxil fumarate: a single-center observational study
Authors: Abe Kensuke , Obara Taku , Kamio Satomi , Kondo Asahi , Imamura Junji , Goto Tatsuya , Ito Toshihiro , Sato Hiroshi , Takahashi Nobuyuki
Published: December 2021

Background

Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF.

Methods

A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of the treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF.

Results

Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. The factors significantly correlated with the decrease in eGFR at 144 weeks on TAF were eGFR and weight at the start of TAF.

Conclusions

In this study, it was confirmed that switching to TAF was effective for Japanese HIV-1-positive patients who had been taking TDF for a long period of time and had a reduced eGFR. It was also found that the transition status depended on the eGFR and weight at the time of switch. Since HIV-1-positive patients in Japan are expected to continue taking TAF for a long time, renal function and body weight should be carefully monitored.
The lived experience of HIV-infected patients in the face of a positive diagnosis of the disease: a phenomenological study
Authors: Imani Behzad , Zandi Shirdel , khazaei Salman , Mirzaei Mohamad
Published: December 2021

Background

AIDS as a human crisis may lead to devastating psychological trauma and stress for patients. Therefore, it is necessary to study different aspects of their lives for better support and care. Accordingly, this study aimed to explain the lived experience of HIV-infected patients in the face of a positive diagnosis of the disease.

Methods

This qualitative study is a descriptive phenomenological study. Sampling was done purposefully and participants were selected based on the inclusion and exclusion criteria. Data collection was conducted, using semi-structured interviews. Data analysis was performed using Colaizzi’s method.

Results

12 AIDS patients participated in this study. As a result of data analysis, 5 main themes and 12 sub-themes were identified, which include: emotional shock (loathing, motivation of social isolation), the fear of the consequences (fear of the death, fear of loneliness, fear of disgrace), the feeling of the guilt (feeling of regret, feeling guilty, feeling of conscience-stricken), the discouragement (suicidal ideation, disappointment), and the escape from reality (denial, trying to hide).

Conclusion

The results of this study showed that patients will experience unpleasant phenomenon in the face of the positive diagnosis of the disease and will be subjected to severe psychological pressures that require attention and support of medical and laboratory centers.
COVID-19 in renal transplant recipients and general population: a comparative study of clinical, laboratory, and radiological features, severity, and outcome
Authors: Monfared Ali , Akhondzadeh Leila , Mousazadeh Mahsa , Jafari Atefeh , Khosravi Masoud , Lebadi Mohammadkazem , Aghajanzadeh Pegah , Haghdar-Saheli Yalda , Movassaghi Ali , Ramezanzadeh Elham , Shobeirian Farzaneh , Kazemnezhad Ehsan , Esmaeili Samaneh
Published: December 2021

Introduction

Coronavirus disease 2019 (COVID-19), a novel disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to millions of deaths worldwide. Kidney transplant recipients (KTRs) are a fragile population due to their immunosuppressed status. However, there are limited studies available comparing this population with the general population regarding clinical symptoms, and laboratory and imaging features as well as disease severity and clinical outcomes.

Methods

A total of 24 KTRs and 40 patients from the general population (control group) were enrolled after applying exclusion criteria. Clinical symptoms, laboratory values, and lung involvement patterns in high-resolution computed tomography (HRCT) were compared between KTRs with COVID-19 and their counterparts from the general population. Moreover, the category of disease severity and adverse outcomes such as intensive care unit (ICU) admission, mechanical ventilation (MV), and mortality rate were also compared between these two groups.

Results

Hypertension was significantly higher among KTRs. Dyspnea was significantly more among the control group (P = 0.045). There was no significant difference in the rest of clinical symptoms (P > 0.05). There was no significant difference in CT features as well, except pleural effusion, which was more prevalent in the control group. A lower absolute lymphocytic count (ALC) and platelet count were observed in KTRs. Renal transplant recipients (RTRs) had a higher elevation in creatinine level than their counterparts. The ICU admission, MV, duration of hospital stay, and mortality as adverse outcomes were not significantly different between the KTR and control groups.

Conclusion

In conclusion, there was no significant difference in the severity and risk of adverse outcomes, including MV, ICU admission, and mortality between KTRs under chronic immunosuppression and the control group.
Sine scleroderma, limited cutaneous, and diffused cutaneous systemic sclerosis survival and predictors of mortality
Authors: De Almeida Chaves Sébastien , Porel Tiphaine , Mounié Mickael , Alric Laurent , Astudillo Léonardo , Huart Antoine , Lairez Olivier , Michaud Martin , Prévot Grégoire , Ribes David , Sailler Laurent , Gaches Francis , Adoue Daniel , Pugnet Gregory
Published: December 2021

Background

Systemic sclerosis (SSc) is associated with a variability of mortality rates in the literature.

Objective

To determine the mortality and its predictors in a long-term follow-up of a bi-centric cohort of SSc patients.

Methods

A retrospective observational study by systematically analyzing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital. Standardized Mortality Ratio (SMR), mortality at 1, 3, 5, 10, and 15 years of disease and causes of death were described. Predictors of mortality using Cox regression were assessed.

Results

Three hundred seventy-five patients were included: 63 with diffuse cutaneous SSc, 279 with limited cutaneous SSc, and 33 with sine scleroderma. The SMR ratio was 1.88 (95% CI 1.46–1.97). The overall survival rates were 97.6% at 1 year, 93.4% at 3 years, 87.1% at 5 years, 77.9% at 10 years, and 61.3% at 15 years. Sixty-nine deaths were recorded. 46.4% were SSc related deaths secondary to interstitial lung disease (ILD) (34.4%), pulmonary hypertension (31.2%), and digestive tract involvement (18.8%). 53.6% were non-related to SSc: cardiovascular disorders (37.8%) and various infections (35.1%) largely distanced those from cancer (13.5%). Four significant independent predictive factors were identified: carbon monoxide diffusing capacity (DLCO) < 70% (HR=3.01; p=0.0053), C-reactive protein (CRP) >5 mg/l (HR=2.13; p=0.0174), cardiac involvement (HR=2.86; p=0.0012), and the fact of being male (HR=3.25; p=0.0004).

Conclusion

Long-term data confirmed high mortality of SSc. Male sex, DLCO <70%, cardiac involvement, and CRP> 5mg/l were identified as independent predictors of mortality.
Genome insights of Enterococcus raffinosus CX012922, isolated from the feces of a Crohn’s disease patient
Authors: Zhao Hailan , Peng Yao , Cai Xunchao , Zhou Yongjian , Zhou Youlian , Huang Hongli , Xu Long , Nie Yuqiang
Published: December 2021

Background

Enterococcus raffinosus is one of the Enterococcus species that often cause nosocomial infections. To date, only one E. raffinosus genome has been completely assembled, and the genomic features have not been characterized. Here, we report the complete genome sequence of the strain CX012922, isolated from the feces of a Crohn’s disease patient, and perform a comparative genome analysis to the relevant Enterococcus spp. strains in silico.

Results

De novo assembly of the sequencing reads of the strain CX012922 generated a circular genome of 2.83 Mb and a circular megaplasmid of 0.98 Mb. Phylogenomic analysis revealed that the strain CX012922 belonged to the E. raffinosus species. By comparative genome analysis, we found that some strains previously identified as E. raffinosus or E. gilvus should be reclassified as novel species. Genome islands (GIs), virulence factors, and antibiotic genes were found in both the genome and the megaplasmid, although pathogenic genes were mainly encoded in the genome. A large proportion of the genes encoded in the megaplasmid were involved in substrate utilization, such as raffinose metabolism. Giant megaplasmids (~1 Mb) equipped with toxin-antitoxin (TA) systems generally formed symbiosis relationships with the genome of E. raffinosus strains.

Conclusions

Enterococcus spp. have a higher species-level diversity than is currently appreciated. The pathogenicity of E. raffinosus is mainly determined by the genome-encoded virulence factors, while the megaplasmid broadens the gene function pool. The symbiosis between the genome and the megaplasmids endows E. raffinosus with large genomic sizes as well as versatile gene functions, especially for their colonization, adaptation, virulence, and pathogenesis in the human gut.