bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive evaluation of connectivity methods for L1000 data
Authors: Lin Kequan , Li Lu , Dai Yifei , Wang Huili , Teng Shuaishuai , Bao Xilinqiqige , Lu Zhi John , Wang Dong
Published: October 2019

The methodologies for evaluating similarities between gene expression profiles of different perturbagens are the key to understanding mechanisms of actions (MoAs) of unknown compounds and finding new indications for existing drugs. L1000-based next-generation Connectivity Map (CMap) data is more than a thousand-fold scale-up of the CMap pilot dataset. Although several systematic evaluations have been performed individually to assess the accuracy of the methodologies for the CMap pilot study, the performance of these methodologies needs to be re-evaluated for the L1000 data. Here, using the drug–drug similarities from the Drug Repurposing Hub database as a benchmark standard, we evaluated six popular published methods for the prediction performance of drug–drug relationships based on the partial area under the receiver operating characteristic (ROC) curve at false positive rates of 0.001, 0.005 and 0.01 (AUC0.001, AUC0.005 and AUC0.01). The similarity evaluating algorithm called ZhangScore was generally superior to other methods and exhibited the highest accuracy at the gene signature sizes ranging from 10 to 200. Further, we tested these methods with an experimentally derived gene signature related to estrogen in breast cancer cells, and the results confirmed that ZhangScore was more accurate than other methods. Moreover, based on scoring results of ZhangScore for the gene signature of TOP2A knockdown, in addition to well-known TOP2A inhibitors, we identified a number of potential inhibitors and at least two of them were the subject of previous investigation. Our studies provide potential guidelines for researchers to choose the suitable connectivity method. The six connectivity methods used in this report have been implemented in R package (https://github.com/Jasonlinchina/RCSM).
Regulation of placentation by the transforming growth factor beta superfamily†
Authors: Adu-Gyamfi Enoch Appiah , Ding Yu-Bin , Wang Ying-Xiong
Published: October 2019

During pregnancy, there is increased expression of some cytokines at the fetal–maternal interface; and the clarification of their roles in trophoblast–endometrium interactions is crucial to understanding the mechanism of placentation. This review addresses the up-to-date reported mechanisms by which the members of the transforming growth factor beta superfamily regulate trophoblast proliferation, differentiation, and invasion of the decidua, which are the main phases of placentation. The available information shows that these cytokines regulate placentation in somehow a synergistic and an antagonistic manner; and that dysregulation of their levels can lead to aberrant placentation. Nevertheless, prospective studies are needed to reconcile some conflicting reports; and identify some unknown mediators involved in the actions of these cytokines before their detailed mechanistic regulation of human placentation could be fully characterized. The TGF beta superfamily are expressed in the placenta, and regulate the process of placentation through the activation of several signaling pathways.
Multisample estimation of bacterial composition matrices in metagenomics data
Authors: Cao Yuanpei , Zhang Anru , Li Hongzhe
Published: October 2019

Metagenomics sequencing is routinely applied to quantify bacterial abundances in microbiome studies, where bacterial composition is estimated based on the sequencing read counts. Due to limited sequencing depth and DNA dropouts, many rare bacterial taxa might not be captured in the final sequencing reads, which results in many zero counts. Naive composition estimation using count normalization leads to many zero proportions, which tend to result in inaccurate estimates of bacterial abundance and diversity. This paper takes a multisample approach to estimation of bacterial abundances in order to borrow information across samples and across species. Empirical results from real datasets suggest that the composition matrix over multiple samples is approximately low rank, which motivates a regularized maximum likelihood estimation with a nuclear norm penalty. An efficient optimization algorithm using the generalized accelerated proximal gradient and Euclidean projection onto simplex space is developed. Theoretical upper bounds and the minimax lower bounds of the estimation errors, measured by the Kullback–Leibler divergence and the Frobenius norm, are established. Simulation studies demonstrate that the proposed estimator outperforms the naive estimators. The method is applied to an analysis of a human gut microbiome dataset.
Spectrum and dosing of urate-lowering drugs in a large cohort of chronic kidney disease patients and their effect on serum urate levels: a cross-sectional analysis from the German Chronic Kidney Disease study
Authors: Kielstein Jan T , Heisterkamp Markus , Jing Jiaojiao , Nadal Jennifer , Schmid Matthias , Kronenberg Florian , Busch Martin , Sommerer Claudia , Lorenzen Johan M , Eckardt Kai-Uwe , Köttgen Anna ,   for the GCKD Study Investigators
Published: October 2019

Background

Despite a plethora of studies on the effect of urate-lowering therapy (ULT) in patients with chronic kidney disease (CKD), current guidelines on the treatment of hyperuricaemia and gout vary, especially concerning the need for dose adjustment of allopurinol, whose main metabolite is accumulating with declining renal function. Data on allopurinol dosing and its relationship to renal function, co-medication and sex and the resulting urate level in large cohorts are missing.

Methods

We studied a subgroup of 2378 patients of the German Chronic Kidney Disease (GCKD) study to determine prescription patterns of ULT among CKD patients under nephrological care and the relationship of ULT dose to urate levels. Prescription and dosing of ULT were manually abstracted from the patient’s paper charts at the baseline visit, in which all currently used medications and their dosing were recorded.

Results

In this cohort, 39.6% were women, the mean estimated glomerular filtration rate (eGFR) was 51.3 ± 19.3 mL/min/1.73 m2 and the mean age was 59.0 ± 12.4 years. Of the 2378 examined patients, 666 (28.0%) received ULT. The dose of ULT was available for 572 patients. The main ULT agent was allopurinol (94.4%), followed by febuxostat (2.9%) and benzbromarone (2.6%). Of the 540 patients who used allopurinol with a reported daily dose, 480 had an eGFR <60 mL/min/1.73 m2 and 320 had an eGFR <45 mL/min/1.73 m2, 31.5% of the latter (n = 101) received a dose >150 mg/day, the recommended maximal dose for this level of eGFR. The prescribed dose was not related to eGFR: the median eGFR for patients taking 100, 150 and 300 mg/day was 40 [interquartile range (IQR) 32–49], 43 (34–52) and 42 (35–54) mL/min/1.73 m2, respectively. Patients with lower doses of allopurinol had higher serum urate levels than patients with higher (than recommended) allopurinol doses. Sex, alcohol intake, eGFR, use of diuretics and treatment with allopurinol were independent determinants of serum urate levels in multivariate regression analysis.

Conclusions

The most frequently used drug to lower serum urate levels in this CKD cohort was allopurinol. Even in patients regularly seen by nephrologists, the dose of allopurinol is often not adjusted to the current eGFR. Patients with higher ULT doses achieved better control of their serum urate levels. Lowering of serum urate in CKD patients requires balancing potential adverse effects of allopurinol with suboptimal control of serum urate levels.
Colesevelam enhances the beneficial effects of brown fat activation on hyperlipidaemia and atherosclerosis development
Authors: Zhou Enchen , Hoeke Geerte , Li Zhuang , Eibergen Arthur C , Schonk Amber W , Koehorst Martijn , Boverhof Renze , Havinga Rick , Kuipers Folkert , Coskun Tamer , Boon Mariëtte R , Groen Albert K , Rensen Patrick C N , Berbée Jimmy F P , Wang Yanan
Published: October 2019

Aims

Brown fat activation accelerates the uptake of cholesterol-enriched remnants by the liver and thereby lowers plasma cholesterol, consequently protecting against atherosclerosis development. Hepatic cholesterol is then converted into bile acids (BAs) that are secreted into the intestine and largely maintained within the enterohepatic circulation. We now aimed to evaluate the effects of prolonged brown fat activation combined with inhibition of intestinal BA reabsorption on plasma cholesterol metabolism and atherosclerosis development.

Methods and results

APOE*3-Leiden.CETP mice with humanized lipoprotein metabolism were treated for 9 weeks with the selective β3-adrenergic receptor (AR) agonist CL316,243 to substantially activate brown fat. Prolonged β3-AR agonism reduced faecal BA excretion (−31%), while markedly increasing plasma levels of total BAs (+258%), cholic acid-derived BAs (+295%), and chenodeoxycholic acid-derived BAs (+217%), and decreasing the expression of hepatic genes involved in BA production. In subsequent experiments, mice were additionally treated with the BA sequestrant Colesevelam to inhibit BA reabsorption. Concomitant intestinal BA sequestration increased faecal BA excretion, normalized plasma BA levels, and reduced hepatic cholesterol. Moreover, concomitant BA sequestration further reduced plasma total cholesterol (−49%) and non-high-density lipoprotein cholesterol (−56%), tended to further attenuate atherosclerotic lesion area (−54%). Concomitant BA sequestration further increased the proportion of lesion-free valves (+34%) and decreased the relative macrophage area within the lesion (−26%), thereby further increasing the plaque stability index (+44%).

Conclusion

BA sequestration prevents the marked accumulation of plasma BAs as induced by prolonged brown fat activation, thereby further improving cholesterol metabolism and reducing atherosclerosis development. These data suggest that combining brown fat activation with BA sequestration is a promising new therapeutic strategy to reduce hyperlipidaemia and cardiovascular diseases.
3-Hydroxyanthralinic acid metabolism controls the hepatic SREBP/lipoprotein axis, inhibits inflammasome activation in macrophages, and decreases atherosclerosis in Ldlr−/− mice
Authors: Berg Martin , Polyzos Konstantinos A , Agardh Hanna , Baumgartner Roland , Forteza Maria J , Kareinen Ilona , Gisterå Anton , Bottcher Gerhard , Hurt-Camejo Eva , Hansson Göran K , Ketelhuth Daniel F J
Published: October 2019

Aims

Atherosclerosis is a chronic inflammatory disease involving immunological and metabolic processes. Metabolism of tryptophan (Trp) via the kynurenine pathway has shown immunomodulatory properties and the ability to modulate atherosclerosis. We identified 3-hydroxyanthranilic acid (3-HAA) as a key metabolite of Trp modulating vascular inflammation and lipid metabolism. The molecular mechanisms driven by 3-HAA in atherosclerosis have not been completely elucidated. In this study, we investigated whether two major signalling pathways, activation of SREBPs and inflammasome, are associated with the 3-HAA-dependent regulation of lipoprotein synthesis and inflammation in the atherogenesis process. Moreover, we examined whether inhibition of endogenous 3-HAA degradation affects hyperlipidaemia and plaque formation.

Methods and results

In vitro, we showed that 3-HAA reduces SREBP-2 expression and nuclear translocation and apolipoprotein B secretion in HepG2 cell cultures, and inhibits inflammasome activation and IL-1β production by macrophages. Using Ldlr−/− mice, we showed that inhibition of 3-HAA 3,4-dioxygenase (HAAO), which increases the endogenous levels of 3-HAA, decreases plasma lipids and atherosclerosis. Notably, HAAO inhibition led to decreased hepatic SREBP-2 mRNA levels and lipid accumulation, and improved liver pathology scores.

Conclusions

We show that the activity of SREBP-2 and the inflammasome can be regulated by 3-HAA metabolism. Moreover, our study highlights that targeting HAAO is a promising strategy to prevent and treat hypercholesterolaemia and atherosclerosis.
Blood flow patterns regulate PCSK9 secretion via MyD88-mediated pro-inflammatory cytokines
Authors: Liu Shijie , Deng Xiaoyan , Zhang Peng , Wang Xianwei , Fan Yubo , Zhou Sichang , Mu Shengyu , Mehta Jawahar L , Ding Zufeng
Published: October 2019

Aims

Blood flow patterns play an important role in the localization of atherosclerosis in the sense that low-flow state is pro-atherogenic, and helical flow is protective against atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism via low-density lipoprotein receptor (LDLr) degradation and is highly expressed in the atherosclerotic tissues. This study was designed to investigate the role of different blood flow patterns in the regulation of PCSK9 expression.

Methods and results

We designed an experimental model guider to generate stable helical flow. Our data showed that compared with normal flow, low-flow state induces whereas helical flow inhibits PCSK9 expression in the rabbit thoracic aorta in an inflammatory state. Our data also identified that TLR4-MyD88-NF-κB signalling plays an important role in PCSK9 expression. On the other hand, TRIF pathway had almost no effect. Further studies showed that the signals downstream of NF-κB, such as pro-inflammatory cytokines (IL-1β, IL-18, MCP-1, IL-6, TNF-α, IL-12, IFNγ, and GM-CSF) directly influence PCSK9 expression. Interestingly, high fat diet further enhanced PCSK9 expression in an inflammatory milieu.

Conclusions

These observations suggest a link between abnormal flow patterns and PCSK9 expression in inflammatory states, which may qualify helical flow and pro-inflammatory cytokines as potential targets to treat PCSK9-related cardiovascular diseases.
Reactome and ORCID—fine-grained credit attribution for community curation
Authors: Viteri Guilherme , Matthews Lisa , Varusai Thawfeek , Gillespie Marc , Milacic Marija , Cook Justin , Weiser Joel , Shorser Solomon , Sidiropoulos Konstantinos , Fabregat Antonio , Haw Robin , Wu Guanming , Stein Lincoln , D’Eustachio Peter , Hermjakob Henning
Published: October 2019

Reactome is a manually curated, open-source, open-data knowledge base of biomolecular pathways. Reactome has always provided clear credit attribution for authors, curators and reviewers through fine-grained annotation of all three roles at the reaction and pathway level. These data are visible in the web interface and provided through the various data download formats. To enhance visibility and credit attribution for the work of authors, curators and reviewers, and to provide additional opportunities for Reactome community engagement, we have implemented key changes to Reactome: contributor names are now fully searchable in the web interface, and contributors can ‘claim’ their contributions to their ORCID profile with a few clicks. In addition, we are reaching out to domain experts to request their help in reviewing and editing Reactome pathways through a new ‘Contribution’ section, highlighting pathways which are awaiting community review.

Database URL: https://reactome.org
Preoperative versus intraoperative image-guided localization of multiple ipsilateral lung nodules
Authors: Chao Yin-Kai , Fang Hsin-Yueh , Pan Kuang-Tse , Wen Chih-Tsung , Hsieh Ming-Ju
Published: October 2019

OBJECTIVES

Computed tomography (CT)-guided localization of multiple ipsilateral pulmonary nodules remains challenging. Hybrid operating rooms equipped with cone-beam CT and laser navigation systems have the potential for improving clinical workflows and patient outcomes.

METHODS

Patients with multiple ipsilateral pulmonary nodules requiring localization were divided according to the localization method [preoperative CT-guided (POCT group) localization versus intraoperative CT-guided (IOCT group) localization]. The 2 groups were compared in terms of procedural efficacy, safety and radiation exposure.

RESULTS

Patients in the IOCT (n = 12) and POCT (n = 42) groups did not differ in terms of demographic and tumour characteristics. Moreover, the success and complication rates were similar. Notably, the IOCT approach allowed multiple nodules to be almost simultaneously localized—resulting in a shorter procedural time [mean difference (MD) −15.83 min, 95% confidence interval (CI) −7.97 to −23.69 min] and lower radiation exposure (MD −15.59 mSv, 95% CI −7.76 to −23.42 mSv) compared with the POCT approach. However, the total time under general anaesthesia was significantly longer in the IOCT group (MD 34.96 min, 95% CI 1.48–68.42 min), despite a similar operating time. The excess time under anaesthesia in the IOCT group can be attributed not only to the procedure per se but also to a longer surgical preparation time (MD 21.63 min, 95% CI 10.07–33.19 min).

CONCLUSIONS

Compared with the POCT approach, IOCT-guided localization performed in a hybrid operating room is associated with a shorter procedural time and less radiation exposure, albeit at the expense of an increased time under general anaesthesia.
Two-dimensional versus three-dimensional Frӓnkel Manoeuvre: a reproducibility study
Authors: Rongo Roberto , Bucci Rosaria , Adaimo Raffaella , Amato Massimo , Martina Stefano , Valletta Rosa , D’antò Vincenzo
Published: October 2019

Background/Objectives

To assess intra- and inter-observer reproducibility of the evaluation of the Frӓnkel Manoeuvre (FM) on three-dimensional (3D) scans and to compare it to the assessment on two-dimensional (2D) pictures.

Materials/Methods

This study included 44 individuals with a skeletal Class II malocclusion [9–16-years old mean age ± standard deviation: 13.5 ± 2.01 years]. All patients had a full Class II molar relationship, overjet ≥6 mm and point A, Nasion, point B angle (ANB) ≥5 degrees. During the FM, each patient was invited to bite in centric occlusion and then to posture the mandible forward to reach a Class I molar relationship. The FM was recorded both by a normal camera and a 3D scanner (3dMD system). Six examiners divided into two groups according to their orthodontic clinical experience (<5 and >10 years), and one gold standard in the evaluation of FM, commented twice (every 15 days) on both 2D photographs (T0 and T2) and 3D scans (T1 and T3). The intra-observer agreement and the inter-observer agreement compared to the gold standard were evaluated by computing the Cohen’s K.

Results

The agreement between observations for each examiner ranged from 0.36 to 1 on 2D pictures (T0 versus T2), and from 0.22 to 0.69 on 3D scans (T1 versus T3). The overall agreement was 0.63 (95 per cent CI = 0.35–0.91) in 2D analysis and 0.5 (95 per cent CI = 0.35–0.64) in 3D analysis.

Conclusions/Implications

The FM was less reproducible when performed on 3D records than on 2D pictures.
Night work and risk of ischaemic heart disease and anti-hypertensive drug use: a cohort study of 145 861 Danish employees
Authors: Larsen Ann D , Rugulies Reiner , Hansen Johnni , Kolstad Henrik A , Hansen Åse Marie , Hannerz Harald , Garde Anne Helene
Published: October 2019

Background

Ischaemic heart disease (IHD) and hypertension are leading causes of mortality and night work has been suspected as a risk factor. Meta-analyses and previous studies are often limited by power and various definitions of exposure and outcomes. This study aimed to investigate if night work increases the risk of IHD or anti-hypertensive drug usage in a large cohort of Danish employees.

Methods

Individual participant data on night work were drawn from the Danish Labour Force Survey (1999–2013). We included 145 861 participants (53% men) 21–59 years of age working 32 h or more per week. Participants with diagnosis or drug use in the year prior to baseline were excluded. Data on outcomes were obtained from nationwide health registers. Using Poisson regression we analyzed incidence rates of the outcomes as functions of night work adjusted for relevant covariates.

Results

We observed 3635 cases of IHD and 20 648 cases used anti-hypertensive drugs. When examining main effects the association of night work with drug use was estimated at rate ratio (RR): 1.05 (95% CI: 1.01–1.09). A sensitivity analysis suggested a dose-response association. The association of night work with IHD was estimated at RR: 1.08 (95% CI: 0.98–1.19). Overall likelihood ratio test showed no statistically significant associations between night work and IHD or drug use when including interactions with sex and socioeconomic status.

Conclusions

Night work was associated with an increased risk of anti-hypertensive drug use. Small estimates suggested a dose-response association. No statistically significant association between night work and IHD were found.
Prevalence and adverse obstetric outcomes of female genital mutilation among women in rural Northern Ghana
Authors: Nonterah Engelbert A , Kanmiki Edmund W , Agorinya Isaiah A , Sakeah Evelyn , Tamimu Mariatu , Kagura Juliana , Kaburise Michael B , Ayamba Emmanuel Y , Nonterah Esmond W , Awuni Denis A , Al-Hassan Majeedallahi , Ofosu Winfred , Awoonor-Williams John K , Oduro Abraham R
Published: October 2019

Background

Female genital mutilation (FGM) is commonly practiced in sub-Saharan Africa and results in adverse pregnancy outcomes among affected women. This paper assessed the prevalence and effects of FGM on pregnancy outcomes in a rural Ghanaian setting.

Methods

We analyzed 9306 delivery records between 2003 and 2013 from the Navrongo War Memorial Hospital. Multivariable logistic regression analyses were used to determine the effects of FGM on pregnancy outcomes such as stillbirth, birth weight, postpartum haemorrhage, caesarean and instrumental delivery. We also assessed differences in the duration of stay in the hospital by FGM status.

Results

A greater proportion of mothers with FGM (24.7%) were older than 35 years compared with those without FGM (7.6%). FGM declined progressively from 28.4% in 2003 to 0.6% in 2013. Mothers with FGM were nearly twice as likely to have caesarean delivery (adjusted odds ratios = 1.85 with 95%CI [1.72, 1.99]) and stillbirths (1.60 [1.21, 2.11]) compared with those without. Similarly, they had a 4-fold increased risk of post-partum haemorrhage (4.69 [3.74, 5.88]) and more than 2-fold risk lacerations/episiotomy (2.57 [1.86, 3.21]) during delivery. Average duration of stay in the hospital was higher for mothers with FGM from 2003 to 2007.

Conclusions

Despite significant decline in prevalence of FGM, adverse obstetric outcomes are still high among affected women. Increased public health education of circumcised women on these outcomes would help improve institutional deliveries and heighten awareness and prompt clinical decisions among healthcare workers. Further scale-up of community level interventions are required to completely eliminate FGM.
Cell-fies: sharing microbiology with global audiences through Instagram
Authors: Hines Hunter N
Published: October 2019

For the dissemination of microbiology and science in general, social media is an underutilized but increasingly powerful tool, and one that transcends traditional avenues for scientific outputs. In order to reach and potentially inspire a deeply interested and general public, scientists should engage with platforms such as Instagram to share their content to an increasingly global audience.
Physical Functional Limitations in a First-Admission Cohort at Midlife: Findings From the Suffolk County Mental Health Project
Authors: Clouston Sean A P , Jonas Katherine , Fochtmann Laura J , Bromet Evelyn J , Kotov Roman
Published: October 2019

Background

Psychosis is a risk factor for aging-related conditions and early mortality. Little is known about the age-specific risk of objectively measured physical functional limitations among individuals with serious mental illness.

Methods

The Suffolk County Mental Health Project is a prospective study of individuals hospitalized for the first time for psychosis. To assess physical functioning at midlife and to identify emerging risk factors for older-age changes, 101 participants with schizophrenia (mean age = 47.2, SD = 8.0 years; 41.6% female) and 112 participants with other psychoses (mean age = 48.2, SD = 9.5 years; 45.5% female) were assessed for chair-rise and balance limitations 20 years after diagnosis. A never-psychotic comparison group of 237 age/sex/geographically matched community controls was similarly assessed (mean age = 50.3, SD = 8.8 years; 44.7% female). Logistic regression was used to examine group differences in prevalence of poor performance and demographic, medical, and treatment correlates.

Results

Chair-rise limitations (45.5% [35.8–55.3]) and balance limitations (17.2% [9.8–24.5]) were common in individuals with schizophrenia. Prevalence of chair-rise limitations was higher in schizophrenia (46.3%) than in other psychotic disorders (31.9%) and never-psychotic group (22.1%), whereas risk of balance limitations was higher in schizophrenia (17.2%) compared with never-psychotic controls (8.1%). Schizophrenia was a significant risk factor for chair-rise (adjusted odds ratio = 3.01 [1.79–5.08], p < .001) and balance limitations (adjusted odds ratio = 2.63, [1.25–5.51], p = .010). Multivariable analysis of symptom severity found avolition was associated with chair-rise limitations, but not balance, independent of diagnosis.

Conclusion

Physical limitations are crucial because they identify existing problems with mobility and portend an increased risk of disability and death. Because participants with schizophrenia were at increased risk of physical limitations, assessments of chair-rise and balance limitations may be critical to monitoring individuals with psychosis.
IKAP—Identifying K mAjor cell Population groups in single-cell RNA-sequencing analysis
Authors: Chen Yun-Ching , Suresh Abhilash , Underbayev Chingiz , Sun Clare , Singh Komudi , Seifuddin Fayaz , Wiestner Adrian , Pirooznia Mehdi
Published: October 2019

Background

In single-cell RNA-sequencing analysis, clustering cells into groups and differentiating cell groups by differentially expressed (DE) genes are 2 separate steps for investigating cell identity. However, the ability to differentiate between cell groups could be affected by clustering. This interdependency often creates a bottleneck in the analysis pipeline, requiring researchers to repeat these 2 steps multiple times by setting different clustering parameters to identify a set of cell groups that are more differentiated and biologically relevant.

Findings

To accelerate this process, we have developed IKAP—an algorithm to identify major cell groups and improve differentiating cell groups by systematically tuning parameters for clustering. We demonstrate that, with default parameters, IKAP successfully identifies major cell types such as T cells, B cells, natural killer cells, and monocytes in 2 peripheral blood mononuclear cell datasets and recovers major cell types in a previously published mouse cortex dataset. These major cell groups identified by IKAP present more distinguishing DE genes compared with cell groups generated by different combinations of clustering parameters. We further show that cell subtypes can be identified by recursively applying IKAP within identified major cell types, thereby delineating cell identities in a multi-layered ontology.

Conclusions

By tuning the clustering parameters to identify major cell groups, IKAP greatly improves the automation of single-cell RNA-sequencing analysis to produce distinguishing DE genes and refine cell ontology using single-cell RNA-sequencing data.
How to do your Social Research Project or Dissertation
Authors: Clark Tom , Foster Liam , Bryman Alan
Published: October 2019

How to do your Social Research Project or Dissertation looks to help readers to navigate research for a project or dissertation. It starts with an introduction to the research process and how to get started. It examines the process of developing an idea. It reviews the available literature. It then considers how to build upon the project idea, the ethical issues, and how to write a proposal. Next it considers sampling, and collecting and analyzing quantitative and qualitative data. Finally, it describes how to evaluate the project and the process of writing up.
Efficacy and safety of surgery for spontaneous pneumothorax in elderly patients
Authors: Nagata Shunichi , Omasa Mitsugu , Tokushige Kosuke , Nakanishi Takao , Motoyama Hideki
Published: October 2019

OBJECTIVES

There is no clear consensus on the surgical indications for spontaneous pneumothorax in elderly patients. In this study, we aimed to assess the efficacy and safety of surgical treatment of spontaneous pneumothorax in patients aged ≥70 years. We also sought to identify the risk factors for postoperative prolonged air leaks and complications in such patients.

METHODS

Data pertaining to 104 elderly patients who underwent surgery out of 206 patients (aged ≥70 years) who were diagnosed with spontaneous pneumothorax at our institution between 1994 and 2018 were retrospectively reviewed. The incidences of postoperative persistent air leaks (≥2 days) and postoperative complications (≥grade 3; Clavien–Dindo classification) were analysed for efficacy and safety assessment, respectively.

RESULTS

Median postoperative air leaks continued for 0 days (range 0–25); 14.4% patients developed ≥grade 3 postoperative complications. On the basis of results of multivariable analysis, it was observed that a higher PaCO2 level was significantly associated with prolonged postoperative air leaks [odds ratio (OR) 1.08, 95% confidence interval (CI) 1.00–1.17; P = 0.047]. Poorer performance status was associated with a significantly increased risk of postoperative complications, as assessed by multivariable analysis (OR 6.13, 95% CI 1.38–27.3; P = 0.017). The recurrence rate was 4.8%; mortality rate of patients was 2.9%. Three-year survival rate after surgery was 73.8%.

CONCLUSIONS

Surgical treatment of spontaneous pneumothorax may be effective and safe in selected elderly patients. Moreover, higher PaCO2 and poorer performance status were independent risk factors for postoperative persistent air leaks and complications, respectively.
Cumulative sum analysis of the learning curve for the preclosure technique using Proglide
Authors: Gao Haoyu , Luo Mingyao , Fang Kun , Fan Bowen , Zhao Jiawei , Xue Yunfei , Shu Chang
Published: October 2019

OBJECTIVES

Our study aims to assess the technical quality and the learning curve of the preclosure technique for a vascular surgeon using Proglide using cumulative sum analysis (CUSUM analysis).

METHODS

This study was designed retrospectively and enrolled 81 consecutive patients with 88 access sites who underwent endovascular aortic repair or thoracic endovascular aortic repair with the preclosure technique using Proglide between July 2017 and February 2018. The patients were divided into 2 groups chronologically: (A) the first 40 cases and (B) the latter 41 cases. Logistic regression analysis was used to assess the impact of technical risk factors on the success of the preclosure technique, and the χ2 test and 1-way ANOVA were applied to analyse the distribution of individual characteristics and risk factors between the 2 groups. CUSUM analysis was adapted to analyse the learning curve and to monitor the technical quality, with a predetermined target failure rate of 5%, an alternative failure rate of 20% and calculated 80% ‘alert’, 95% ‘alarm’ and 80% ‘reassurance’ lines.

RESULTS

Primary technical success was obtained in 81 (92.05%) access sites. There were no significant correlations between primary technical success and risk factors, including, common femoral artery diameter (P = 0.88), common femoral artery depth from the skin (P =0.94), the level of common femoral artery calcification (P =0.86) and size of sheath (P =0.96). Moreover, the distribution of related risk factors was not significantly different between groups A and B. CUSUM analysis showed that the cumulative failure rate never crossed the 80% ‘alert’ and 95% ‘alarm’ lines. Additionally, the failure rate began to approach the 80% ‘reassurance’ line after ∼22 cases and crossed the 80% ‘reassurance’ line after 36 cases.

CONCLUSIONS

The technique of totally percutaneous access using Proglide is safe and effective for an experienced vascular surgeon, even if the operator has no previous experience with any preclosure techniques. CUSUM analysis showed that 36 cases are necessary to achieve the target failure rate of 5%.
Key aspects and feasibility assessment of a proposed wind farm in Jordan
Authors: Al-Addous Mohammad , Saidan Motasem , Bdour Mathhar , Dalala Zakariya , Albatayneh Aiman , Class Christina B
Published: October 2019

To tackle climate change and secure energy supplies, many countries invest heavily on wind energy as it is a clean source and is becoming more cost effective with the technological advancement and increased capacity per unit installed. The investigation of the availability of wind resources is an essential step of any feasibility study of a wind farm project and is vital for securing financial resources. With this intent, the main aspects for designing a wind farm at Ajloun (north of Jordan) is investigated and wind energy potential is determined based on available wind data. Based on the site characteristic, the required infrastructure is highlighted, including the turbine array layout and the pattern of connections with the external transmission lines. The investigation of the feasibility of the project includes an appraisal of social and environmental consequences of constructing the wind farm project. The results show that the selected location for the wind farm is encouraging and has a promising profit potential. The findings estimate the annual electricity generation of the wind farm at 379659.51 MWh, with a breakeven selling point of around $30.03/MWh, at a highly competitive price. However, with an estimated selling price of $36.65/MWh on average, it will settle the interest rate demanded by the banks that have an internal rate of return of 7%. No major issues with geotechnical and environmental issues were identified with respect to the project.
Ulrich Bundles on Three-Dimensional Scrolls
Authors: Fania Maria Lucia , Lelli-Chiesa Margherita , Pons-Llopis Joan
Published: October 2019

In this paper we construct Ulrich bundles of low rank on three-dimensional scrolls (with respect to the tautological line bundle). We pay special attention to the four types of three-fold scrolls in ${\mathbb{P}}^5$, which were classified in [31].
The Use of Large-Particle Aerosol Exposure to Nipah Virus to Mimic Human Neurological Disease Manifestations in the African Green Monkey
Authors: Lee Ji Hyun , Hammoud Dima A , Cong Yu , Huzella Louis M , Castro Marcelo A , Solomon Jeffrey , Laux Joseph , Lackemeyer Matthew , Bohannon J Kyle , Rojas Oscar , Byrum Russ , Adams Ricky , Ragland Danny , St Claire Marisa , Munster Vincent , Holbrook Michael R
Published: October 2019

Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 μm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.
Governing ignorance through abduction
Authors: Magnani Lorenzo
Published: October 2019

I will analyse three fundamental ways of governing ignorance though abduction, which are essential from an eco-cognitive and eco-logical point of view, in which the central role in human cognition of natural and artefactual environment is taken into account. First of all, according to the so-called GW-schema, proposed by Gabbay and Woods, abduction presents an ignorance-preserving or (ignorance-mitigating) character: given the fact that the abduced hypotheses aim at becoming truths, the basic ignorance is neither solved nor left untouched. Second, I will contend that abduction is not always ignorance preserving but also knowledge enhancing. Indeed, according to the eco-cognitive model of abduction, I myself have recently proposed, we can easily see that, occasionally, knowledge can be immediately increased (and ignorance ‘killed’) through abduction: in this perspective, abduction does not have to be rigidly conceptualized as an inference to the best explanation in the received sense, which is as an inference that, to grant truth, also takes advantage of an empirical evaluation phase or an inductive phase, as Peirce classified it. Finally, it is important to stress that abductive cognition is at the roots of two fundamental cognitive processes. On one side, abductive cognition constructs (and/or takes advantage of the exploitation of) embodiments, external representations, enactions, artefacts and props, which involve ignorant entities suitably transformed in cognitive representations and/or devices. On the other side, abductive cognition dominates those ‘special’ cognitive creative processes that lead to what I call the disseminated ‘computational domestication of ignorant entities’: I will illustrate the example of the recent unconventional computational domestication of ignorant entities, which creates novel cognitive embodiments (morphological computation).
Probability as a modal operator: the possibilities of its combination with other modalities
Authors: Guallart Nino
Published: October 2019

In this work we examine some of the possibilities of combining a simple probability operator with other modal operators, in particular with a belief operator. We will examine the semantics of two possible situations for expressing probabilistic belief or the lack of it, a simple subjective probability operator (SPO) versus the composition of a belief operator, plus an objective modal operator (BOP). We will study their interpretations in two probabilistic semantics: a relational Kripkean one and a variation of neighbourhood semantics, showing that the latter is able to represent the lack of probabilistic belief more directly, just with the SPO, whereas relational semantics needs the combination of BOP probability to represent lack of belief.
Growth of the tropical Pinus kesiya as influenced by climate and nutrient availability along an elevational gradient
Authors: Ho Le Tuan , Schneider Raimund , Thomas Frank M
Published: October 2019

Aims

In contrast to temperate regions, the reasons for growth reductions of individual tree species along elevational gradients in tropical mountain ranges are poorly known, especially for tropical conifers. We aimed at testing whether climatic or edaphic conditions are responsible for the reduced growth of Pinus kesiya, a widely distributed pine species of southern and south-eastern Asia, at higher elevations.

Methods

We analysed the stem diameter increment and the isotope discrimination against 13C (△ 13C) in tree rings of P. kesiya along an elevational gradient of ~900 to ~2000 m a.s.l. in the mountain ranges of South-Central Vietnam, and related growth to △  13C and to climatic and edaphic variables.

Important findings

We found no consistent correlation patterns between the basal area increment (BAI) of the trees and temperature or precipitation. In contrast, across the elevational gradient, we obtained significantly negative correlations of BAI with △  13C and with the C/N ratios and the δ 15N signature of the upper mineral soil. BAI was positively correlated with the concentrations of plant-available phosphorus (Pa) and of “base” cations (calcium, magnesium, potassium) in the soil. We conclude that lower temperatures at higher elevations exert an indirect effect on tree growth by inducing higher C/N ratios and by reducing the rate of nitrogen (N) and P mineralization, which may be further hampered by lower concentrations of “base” cations (upon enhanced leaching by precipitation) and a negative feedback from low availability of mineralized N and P at higher elevations. Our results may be transferable to the uppermost growth limit of P. kesiya and to other montane regions of the species’ occurrence.
Benign Pancreatic Hyperenzymemia, Also Known as Gullo’s Syndrome
Authors: Rosell-Camps Antonio , Martínez-Cepas Patricia , Riera-Llodrá Joana María , Ventura-Espejo Laura , Riutord-Arrom Nadal
Published: October 2019

Benign pancreatic hyperenzymemia, also known as Gullo’s syndrome, is a little-known syndrome first described in 1996 in patients studied for an elevation of pancreatic enzymes while otherwise being asymptomatic. We describe the case of a 2-year-old patient who was found to have significant elevation of amylase and lipase levels while he was asymptomatic. Blood tests and imaging tests were performed to determine the etiology, but they gave normal results. The enzyme elevation can even be 10 times the normal value of the enzyme, and only 1 enzyme may elevate, although most often all pancreatic enzymes are elevated. The etiology is not known, although several hypotheses have been suggested. This enzyme elevation is described both in adults and children and also sporadically or with a familial pattern. Knowledge of it can limit the performance of the multiple complementary test, some of which are very invasive in patients who have elevated pancreatic enzymes while they are asymptomatic. It knowledge allows us to confirm a benign prognosis about it and reassure the family about this disease and that in the end it will not require aggressive treatments such as surgery or chemotherapy.
Towards 3D modelling of convection in planetesimals and meteorite parent bodies
Authors: Neumann Wladimir
Published: October 2019

Observations of asteroid belt members, investigations of meteorites and thermal evolution models converge on the paradigm of the ubiquity of melting processes in the planetesimals of the early Solar system. At least partial melting of planetesimals that fulfilled size and accretion time requirements to surpass the solidus temperatures of metal and silicates led to the weakening of the rock due to the interstitial melt. A decrease of the viscosity relative to melt-free material facilitates solid-state convection on partially molten bodies. Additional melting can produce liquid-like layers with suspended particles, i.e. magma oceans. Thermal evolution models indicate that partially molten layers can occur in the interior of undifferentiated bodies and in silicate mantles of differentiated ones. They can exist before a magma ocean forms or after it solidifies and above a whole-mantle magma ocean or below a shallow magma ocean. Thus, convection is likely. Attempts to model and to quantify the effects of convection in planetesimals remain rare. This study discusses the possibility of solid-state convection in partially molten planetesimals, presents a first-order comparison of a 3D mantle convection model with a conduction model taking a Vesta-sized body as an example and illustrates the importance of convection for meteorite parent bodies.
Tomopeas ravus (Chiroptera: Molossidae)
Authors: Velazco Paúl M , Kline Kerry A
Published: October 2019

Tomopeas ravus Miller, 1900 is a bat commonly called Peruvian crevice-dwelling bat. It is the only representative of the subfamily Tomopeatinae and endemic to the coastal desert of Peru where it is associated with woody savanna ecosystems and narrow rock crevices. Globally, it is considered “Endangered” by the International Union for Conservation of Nature and Natural Resources, mostly due to the ongoing population reduction and small and fragmented geographic range.
EWAS Data Hub: a resource of DNA methylation array data and metadata
Authors: Xiong Zhuang , Li Mengwei , Yang Fei , Ma Yingke , Sang Jian , Li Rujiao , Li Zhaohua , Zhang Zhang , Bao Yiming
Published: October 2019

Epigenome-Wide Association Study (EWAS) has become an effective strategy to explore epigenetic basis of complex traits. Over the past decade, a large amount of epigenetic data, especially those sourced from DNA methylation array, has been accumulated as the result of numerous EWAS projects. We present EWAS Data Hub (https://bigd.big.ac.cn/ewas/datahub), a resource for collecting and normalizing DNA methylation array data as well as archiving associated metadata. The current release of EWAS Data Hub integrates a comprehensive collection of DNA methylation array data from 75 344 samples and employs an effective normalization method to remove batch effects among different datasets. Accordingly, taking advantages of both massive high-quality DNA methylation data and standardized metadata, EWAS Data Hub provides reference DNA methylation profiles under different contexts, involving 81 tissues/cell types (that contain 25 brain parts and 25 blood cell types), six ancestry categories, and 67 diseases (including 39 cancers). In summary, EWAS Data Hub bears great promise to aid the retrieval and discovery of methylation-based biomarkers for phenotype characterization, clinical treatment and health care.
Recognition and processing of branched DNA substrates by Slx1–Slx4 nuclease
Authors: Gaur Vineet , Ziajko Weronika , Nirwal Shivlee , Szlachcic Aleksandra , Gapińska Marta , Nowotny Marcin
Published: October 2019

Structure-selective endonucleases cleave branched DNA substrates. Slx1 is unique among structure-selective nucleases because it can cleave all branched DNA structures at multiple sites near the branch point. The mechanism behind this broad range of activity is unknown. The present study structurally and biochemically investigated fungal Slx1 to define a new protein interface that binds the non-cleaved arm of branched DNAs. The DNA arm bound at this new site was positioned at a sharp angle relative to the arm that was modeled to interact with the active site, implying that Slx1 uses DNA bending to localize the branch point as a flexible discontinuity in DNA. DNA binding at the new interface promoted a disorder-order transition in a region of the protein that was located in the vicinity of the active site, potentially participating in its formation. This appears to be a safety mechanism that ensures that DNA cleavage occurs only when the new interface is occupied by the non-cleaved DNA arm. Models of Slx1 that interacted with various branched DNA substrates were prepared. These models explain the way in which Slx1 cuts DNA toward the 3′ end away from the branch point and elucidate the unique ability of Slx1 to cleave various DNA structures.