bluuebunny/crossref_metadata_2025 huggingface dataset:
Soluble form of suppression of tumorigenicity-2 predicts clinical stability of inpatients with community-acquired pneumonia
Authors: Zeng Yifeng , Xue Mingshan , Zhang Teng , Sun Shixue , Lin Runpei , Li Ning , Zheng Peiyan , Zhen Yingjie , Hu Haisheng , Zhang Xiaohua Douglas , Sun Baoqing
Published: July 2021

The soluble form of the suppression of tumorigenicity-2 (sST2) is a biomarker for risk classification and prognosis of heart failure, and its production and secretion in the alveolar epithelium are significantly correlated with the inflammation-inducing in pulmonary diseases. However, the predictive value of sST2 in pulmonary disease had not been widely studied. This study investigated the potential value in prognosis and risk classification of sST2 in patients with community-acquired pneumonia. Clinical data of ninety-three CAP inpatients were retrieved and their sST2 and other clinical indices were studied. Cox regression models were constructed to probe the sST2’s predictive value for patients’ restoring clinical stability and its additive effect on pneumonia severity index and CURB-65 scores. Patients who did not reach clinical stability within the defined time (30 days from hospitalization) have had significantly higher levels of sST2 at admission ( P <  0.05). In univariate and multivariate Cox regression analysis, a high sST2 level (≥72.8 ng/mL) was an independent reverse predictor of clinical stability ( P < 0.05). The Cox regression model combined with sST2 and CURB-65 (AUC: 0.96) provided a more accurate risk classification than CURB-65 (AUC:0.89) alone (NRI: 1.18, IDI: 0.16, P < 0.05). The Cox regression model combined with sST2 and pneumonia severity index (AUC: 0.96) also provided a more accurate risk classification than pneumonia severity index (AUC:0.93) alone (NRI: 0.06; IDI: 0.06, P < 0.05). sST2 at admission can be used as an independent early prognostic indicator for CAP patients. Moreover, it can improve the predictive power of CURB-65 and pneumonia severity index score.
Exploring the impact of pharmacist comprehensive annual care plans on perceived quality of chronic illness care by patients in Alberta, Canada
Authors: Necyk Candace , Johnson Jeffrey A. , Tsuyuki Ross T. , Eurich Dean T.
Published: July 2021

Background:

In 2012, the Government of Alberta introduced a funding program to remunerate pharmacists to develop a comprehensive annual care plan (CACP) for patients with complex needs. The objective of this study is to explore patients’ perceptions of the care they received through the pharmacist CACP program in Alberta.

Methods:

We invited 3442 patients who received a pharmacist-billed CACP within the previous 3 months and 6888 matched controls across Alberta to complete an online questionnaire. The questionnaire consisted of the short version Patient Assessment of Chronic Illness Care (PACIC-11), with 3 additional pharmacy-specific assessment questions added. Additional questions related to health status and demographics were also included.

Results:

Overall, most patients indicated a low level of chronic illness care by pharmacists, with few differences noted between CACP patients and non-CACP controls. Of note, controls reported higher quality of care for 5 domains within the adapted PACIC-like tool compared with CACP patients ( p < 0.05 for all). Interestingly, only 79 (44%) of CACP patients reported that they had received a CACP, whereas only 192 (66%) of control patients reported that they did not receive a care plan. In a sensitivity analysis including only these respondents, individuals who received a CACP perceived a significantly higher quality of chronic illness care across all PACIC domains.

Conclusion:

Overall, chronic illness care incentivized by the pharmacist CACP program in Alberta is perceived to be moderate to low. When limited to respondents who explicitly recognized receiving the service or not, the perceptions of quality of care were more positive. This suggests that better implementation of CACP by pharmacists may be associated with improved quality of care and that some redesign is needed to engage patients more. Can Pharm J (Ott) 2021;154:xx-xx.
Caring for a child with a life limiting condition: The experiences of nurses in an intellectual disability service provider
Authors: Connor Eilis O , Corcoran Yvonne
Published: July 2021

This study elicited the experiences of nurses caring for children with life-limiting conditions and their family, within a community based intellectual disability service. A qualitative descriptive research approach was adopted where purposeful sampling recruited 10 participants. Data was collected using one to one semi-structured interviews and was subsequently analysed using qualitative thematic content analysis. The findings identified a range of complexities unique to the care of children with life-limiting conditions in the intellectual disability setting. From the findings, it is clear that this is a population of highly skilled nurses who work in a challenging and complex area of practice. Further supports are required in order to meet the practice needs and support the emotional needs of this population of nurses. In doing so, high quality practice within the area will be promoted, thereby ensuring high quality care for the children and families within the disability service.
Free states for free citizens!? Arguments for a republicanism of plural polities
Authors: Meine Anna
Published: July 2021

The paper assesses the questions if and, if yes, how the republican conception of free statehood can and should inform a compelling understanding of a legitimate post-Westphalian political order. To answer these questions, it, first, reconstructs the foundational arguments of republican internationalists in favour of free states and, second, assesses the points of contention republican cosmopolitans raise. Third, it develops an alternative approach, a republicanism of plural polities: Based on a relational and multi-dimensional understanding of citizenship, the paper questions the strong internationalist reliance on the citizenship-state-nexus and on statehood in general, but also takes issue with cosmopolitans’ neglect of the boundedness of democratic self-determination. A republicanism of plural polities as a multi-perspectival approach to democratic institution-building in and beyond the state is open to constellations of plural polities of different forms and on different political levels while simultaneously recognising the particularity of each ‘free polity’. It thereby adds a new dimension to debates on the political forms legitimate institutions can assume under post-Westphalian conditions and opens avenues for research on inter-polity relations, on more complex constellations of self-rule and shared rule as well as of multilateral decision-making, on sovereignty and independence. The latter are exemplified by reference to the European context.
Does regulation induce cost efficiency in electricity distribution utilities? Use of stochastic cost frontier analysis for the Indian states
Authors: Nandan Amit , Mallick Hrushikesh
Published: July 2021

To overcome the macroeconomic crisis of the early 1990s, the Government of India persuaded the state governments to adopt market-oriented reforms for loss-making state public sector undertakings in general and power sector utilities in particular with an aim to limit the overall size of the public sector. This led the state governments to undertake unbundling of their vertically integrated State Electricity Boards (SEBs), establish independent regulatory bodies in the form of State Electricity Regulatory Commissions (SERCs) to regulate the power sector, and allow for an active participation of private sector. Given this backdrop, the present study attempts to examine the effect of establishment of SERCs on the cost-efficiency of electricity distribution in the Indian states. Thereby, it evaluates whether the establishment of SERCs has induced efficiency gains in the electricity distribution. Estimating a Cobb-Douglas stochastic cost frontier function, it finds that the establishment of independent regulators in various states has resulted in significant improvements in the cost-efficiency in the electricity distribution.
Diagnosis of Anosmia and Hyposmia: A Systematic Review
Authors: Saltagi Abdul K. , Saltagi Mohamad Z. , Nag Amit K. , Wu Arthur W. , Higgins Thomas S. , Knisely Anna , Ting Jonathan Y. , Illing Elisa A.
Published: July 2021

Background

Anosmia and hyposmia have many etiologies, including trauma, chronic sinusitis, neoplasms, and respiratory viral infections such as rhinovirus and SARS-CoV-2. We aimed to systematically review the literature on the diagnostic evaluation of anosmia/hyposmia.

Methods

PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990 using terms combined with Medical Subject Headings (MeSH). We included articles evaluating diagnostic modalities for anosmia, written in the English language, used original data, and had two or more patients.

Results

A total of 2065 unique titles were returned upon the initial search. Of these, 226 abstracts were examined, yielding 27 full-text articles meeting inclusion criteria (Level of evidence ranging from 1 to 4; most level 2). The studies included a total of 13,577 patients. The most utilized diagnostic tools were orthonasal smell tests (such as the Sniffin’ Sticks and the UPSIT, along with validated abridged smell tests). Though various imaging modalities (including MRI and CT) were frequently mentioned in the workup of olfactory dysfunction, routine imaging was not used to primarily diagnose smell loss.

Conclusion

The literature includes several studies on validity and reliability for various smell tests in diagnosing anosmia. Along with a thorough history and physical, validated orthonasal smell tests should be part of the workup of the patient with suspected olfactory dysfunction. The most widely studied modality was MRI, but criteria for the timing and sequence of imaging modalities was heterogenous.
Interpersonal Predictors of Suicide Ideation and Attempt Among Early Adolescents
Authors: Sallee Emily , Ng Kok-Mun , Cazares-Cervantes Abraham
Published: July 2021

Despite the growing epidemic of suicide ideation and attempt in adolescents, there is a lack of theory-based, empirical research to shed light on these issues in this population and inform school counselors’ preventive and responsive practices. We utilized Joiner’s Interpersonal Theory of Suicide (IPTS) to examine the extent to which the interpersonal constructs of perceived burdensomeness and thwarted belongingness predicted adolescent suicide ideation and attempt by conducting two binomial logistic regressions on archival data from the 2017 eighth-grade Oregon Healthy Teens Survey. Six of the seven selected proxy items were statistically significant in each logistic model, with slight variance between the two. Our findings suggest that the interpersonal constructs of the IPTS are applicable to early adolescents and may be used to inform suicide prevention and intervention efforts among this population in school settings.
Horseshoe Patterns: Visualizing Partisan Media Trust in Germany
Authors: Clemm von Hohenberg Bernhard , Bauer Paul C.
Published: July 2021

A trusted media is crucial for a politically informed citizenry, yet media trust has become fragile in many Western countries. An underexplored aspect is the link between media (dis)trust and populism. The authors visualize media trust across news outlets and partisanship in Germany, for both mainstream and “alternative” news sources. For each source, average trust is grouped by partisanship and sorted from left to right, allowing within-source comparisons. The authors find an intriguing horseshoe pattern for mainstream media sources, for which voters of both populist left-wing and right-wing parties express lower levels of trust. The underlying distribution of individual responses reveals that voters of the right-wing populist party are especially likely to “not at all” trust the mainstream outlets that otherwise enjoy high levels of trust. The media trust gap between populist and centrist voters disappears for alternative sources, for which trust is generally low.
Three-Dimensional Imaging of Displaced Intra-articular Calcaneal Fractures Correlates With the Perioperative Diagnosis
Authors: Misselyn Dominique , Schepers Tim , Buckley Richard , Swords Michael , Matricali Giovanni , Nijs Stefaan
Published: July 2021

Background:

Intra-articular calcaneal fractures are complex injuries, and CT imaging has become the standard imaging in the preoperative assessment. Most classifications of these fractures are CT-based but have been associated with limited interobserver agreement. Three-dimensional imaging has become widely available and may give a better perspective but often with 1 image only. There is not much evidence of the added value of this imaging, compared with the CT imaging.

Methods:

Eight experienced trauma surgeons assessed 28 different intra-articular calcaneal fractures, on conventional radiology (CR), CT, and 3-D imaging. All had extensive experience in the diagnosis and treatment of this difficult injury. The main questions concerned Sanders classification, the severity of the injury and the difficulty of the operative procedure, choice of approach, and choice of procedure.

Results:

The classical 2-D CT imaging of the fractures were associated with a higher Sanders classification ranking, compared with the 3-D imaging scores. However, the interobserver agreement, as measured by the Fleiss kappa, was low for all 3 imaging modalities. We found more frequent Sanders III and IV classifications with CT scan imaging compared with 3-D imaging or CR. The scores obtained after assessing 3-D imaging were also not statistically significantly different from the scores of a consensus achieved by 2 authors and based on the 3 imaging modalities and the perioperative diagnosis.

Conclusion:

The 3-D imaging may result in a more realistic view, reducing the frequency of classifying Sanders III fractures than with the 2-D CT imaging series. 3-D imaging may be more reliable than CT in the planning of operative treatment of displaced intra-articular calcaneal fractures.

Level of Evidence:

Level III.
20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment
Authors: Margolin Leon , Luchins Jeremy , Margolin Daniel , Margolin Michelle , Lefkowitz Sanford
Published: July 2021

Objectives and Setting.

As the lethal COVID-19 pandemic enters its second year, the need for effective modalities of alleviation remains urgent. This includes modalities that can readily be used by the public to reduce disease spread and severity. Such preventive measures and early-stage treatments may temper the immediacy of demand for advanced anti-COVID measures (drugs, antibodies, vaccines) and help relieve strain also on other health system resources.

Design and Participants.

We present results of a clinical study with a multi-component OTC “core formulation” regimen used in a multiply exposed adult population. Analysis of clinical outcome data from our sample of over 100 subjects − comprised of roughly equal sized regimen-compliant (test) and non-compliant (control) groups meeting equivalent inclusion criteria − demonstrates a strong statistical significance in favor of use of the core formulations.

Results.

While both groups were moderate in size, the difference between them in outcomes over the 20-week study period was large and stark: Just under 4% of the compliant test group presented flu-like symptoms, but none of the test group was COVID-positive; whereas 20% of the non-compliant control group presented flu-like symptoms, three-quarters of whom (15% overall of the control group) were COVID-positive.

Conclusions.

Offering a low cost, readily implemented anti-viral approach, the study regimen may serve, at the least, as a stopgap modality and, perhaps, as a useful tool in combatting the pandemic.
The impact of the disease burden on the quality of life of cluster headache patients
Authors: Pohl Heiko , Gantenbein Andreas R , Sandor Peter S , Schoenen Jean , Andrée Colette
Published: July 2021

Background:

Cluster headache cannot be cured, and not all attacks can be aborted or prevented. Nevertheless, therapeutic guidelines focus solely on the attacks and ignore reverberations of the disorder on patients’ lives. However, it is likely that not only pain reduces patients’ quality of life (QoL).

Objective:

To investigate whether the interictal burden independently influence the QoL of subjects suffering from cluster headache.

Methods:

In this cross-sectional study, we asked patients with a self-reported cluster headache diagnosis to answer a modified EUROLIGHT questionnaire that included the EURO-HIS QoL scale. We built a generalised linear model and included the QoL as the dependent variable. Independent variables comprised both the ictal and the interictal burden.

Results:

The data of 625 participants entered the analysis. Several aspects of the interictal burden independently reduced the QoL. Among them were fear of pain, self-concealment, and private life difficulties due to the disorder.

Conclusion:

Both the ictal and the interictal burden of cluster headache independently reduce patients’ QoL. We advocate adopting a more holistic approach to cluster headache management extending the focus towards the afflicted person and their QoL, which would generate novel therapeutic goals and strategies, complementary to treating and preventing cluster headache attacks.
Age-related differences in resting state functional connectivity in pediatric migraine
Authors: Bell Tiffany , Khaira Akashroop , Stokoe Mehak , Webb Megan , Noel Melanie , Amoozegar Farnaz , Harris Ashley D.
Published: July 2021

Background

Migraine affects roughly 10% of youth aged 5–15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes.

Methods

Using independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7–15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis.

Results

We show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks.

Conclusions

We demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.
Serum iron status and the risk of breast cancer in the European population: a two-sample Mendelian randomisation study
Authors: Hou Chenyang , Hou Qingzhi , Xie Xing , Wang Huifeng , Chen Yueliang , Lu Tingxi , Wu Qunying , Liang Yongcong , Hu Yanling , Mao Yuang
Published: July 2021

Background

Previous observational studies have provided conflicting results on the association between serum iron status and the risk of breast cancer. Considering the relevance of this relationship to breast cancer prevention, its elucidation is warranted.

Object

We used a two-sample Mendelian randomisation (MR) study to explore the causal relationship between serum iron status and the risk of breast cancer.

Method

To select single nucleotide polymorphisms (SNPs) that could be used as instrumental variables for iron status, we used the Genetics of Iron Status consortium, which includes 11 discovery and 8 replication cohorts, encompassing 48,972 individuals of European descent. Moreover, we used the OncoArray network to select SNPs that could be considered instrumental variables for the outcome of interest (breast cancer); this dataset included 122,977 individuals of European descent with breast cancer and 105,974 peers without breast cancer. Both conservative (SNPs associated with overall iron status markers) and liberal (SNPs associated with the levels of at least one iron status marker) approaches were used as part of the MR analysis. For the former, we used an inverse-variance weighted (IVW) method, whereas for the latter, we used the IVW, MR-Egger regression, weighted median and simple mode methods.

Results

When the conservative approach was used, iron status showed no significant association with the risk of breast cancer or any of its subtypes. However, when the liberal approach was used, transferrin levels were found to be positively associated with the risk of ER-negative breast cancer based on the simple mode method (OR for MR, 1.225; 95% CI, 1.064, 1.410; P = 0.030). Nevertheless, the levels of the other iron status markers showed no association with the risk of breast cancer or its subtypes (P > 0.05).

Conclusion

In our MR study, the liberal approach suggested that changes in the concentration of transferrin could increase the risk of ER-negative breast cancer, although the levels of other iron status markers had no effect on the risk of breast cancer or its subtypes. This should be verified in future studies.
Penile Mondor’s in a Covid-19 patient on prophylactic anti-thrombosis with rivaroxaban: a case report
Authors: Eren Murat Tuğrul , Özveri Hakan , Kurtoğlu Hilal
Published: July 2021

Background

Penile Mondor’s disease (PMD) is thrombophlebitis of the superficial dorsal vein of the penis. Following the occurrence of thrombotic events in the affected veins, the lumen often becomes occluded with fibrin and inflammatory cells. A hyper-coagulative state is one of the underlying causes although most cases of PMD are idiopathic. Coronavirus disease-2019 infection (COVID-19) is associated with frequent thrombotic events. Inflammation and thrombosis play a central role in the course and outcome of COVID-19, which can predispose to both venous and arterial thromboembolism. In this report, we present a 33-year-old male patient diagnosed with PMD during the subacute phase of COVID-19 infection while on prophylactic antithrombotic treatment.

Case Presentation

A 33-year-old male patient was diagnosed as PMD which occurred during the subacute phase of COVID-19 infection, while he was on active treatment of COVID-19 by prophylactic antithrombotic Rivaroxaban 15 mg therapy and curative antiviral medication. There was no recent sexual intercourse or trauma to the genitals. His PCR test for COVID-19 had become negative, and antibody test was positive at the time of his PMD’s onset. Rivaroxaban was replaced by Enoxaparin (8000 IU/0.8 ml.), a low molecular weight heparin administered subcutaneously and twice daily. On the third day of this medication, all coagulative measurements returned to normal. PMD disappeared in the second week.

Conclusion

Low-dose Rivaroxaban 15 mg is not safe for some COVID-19-associated thromboembolism prophylaxis, and careful follow-up is critical due to the possibility of a wide range of pathologic thrombotic manifestations in COVID-19 infection.
Hypergraph models of biological networks to identify genes critical to pathogenic viral response
Authors: Feng Song , Heath Emily , Jefferson Brett , Joslyn Cliff , Kvinge Henry , Mitchell Hugh D. , Praggastis Brenda , Eisfeld Amie J. , Sims Amy C. , Thackray Larissa B. , Fan Shufang , Walters Kevin B. , Halfmann Peter J. , Westhoff-Smith Danielle , Tan Qing , Menachery Vineet D. , Sheahan Timothy P. , Cockrell Adam S. , Kocher Jacob F. , Stratton Kelly G. , Heller Natalie C. , Bramer Lisa M. , Diamond Michael S. , Baric Ralph S. , Waters Katrina M. , Kawaoka Yoshihiro , McDermott Jason E. , Purvine Emilie
Published: July 2021

Background

Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets.

Results

We compiled a novel data set of transcriptional host response to pathogenic viral infections and formulated relationships between genes as a hypergraph where hyperedges represent significantly perturbed genes, and vertices represent individual biological samples with specific experimental conditions. We find that hypergraph betweenness centrality is a superior method for identification of genes important to viral response when compared with graph centrality.

Conclusions

Our results demonstrate the utility of using hypergraphs to represent complex biological systems and highlight central important responses in common to a variety of highly pathogenic viruses.
Feature selection and causal analysis for microbiome studies in the presence of confounding using standardization
Authors: Goren Emily , Wang Chong , He Zhulin , Sheflin Amy M. , Chiniquy Dawn , Prenni Jessica E. , Tringe Susannah , Schachtman Daniel P. , Liu Peng
Published: July 2021

Background

Microbiome studies have uncovered associations between microbes and human, animal, and plant health outcomes. This has led to an interest in developing microbial interventions for treatment of disease and optimization of crop yields which requires identification of microbiome features that impact the outcome in the population of interest. That task is challenging because of the high dimensionality of microbiome data and the confounding that results from the complex and dynamic interactions among host, environment, and microbiome. In the presence of such confounding, variable selection and estimation procedures may have unsatisfactory performance in identifying microbial features with an effect on the outcome.

Results

In this manuscript, we aim to estimate population-level effects of individual microbiome features while controlling for confounding by a categorical variable. Due to the high dimensionality and confounding-induced correlation between features, we propose feature screening, selection, and estimation conditional on each stratum of the confounder followed by a standardization approach to estimation of population-level effects of individual features. Comprehensive simulation studies demonstrate the advantages of our approach in recovering relevant features. Utilizing a potential-outcomes framework, we outline assumptions required to ascribe causal, rather than associational, interpretations to the identified microbiome effects. We conducted an agricultural study of the rhizosphere microbiome of sorghum in which nitrogen fertilizer application is a confounding variable. In this study, the proposed approach identified microbial taxa that are consistent with biological understanding of potential plant-microbe interactions.

Conclusions

Standardization enables more accurate identification of individual microbiome features with an effect on the outcome of interest compared to other variable selection and estimation procedures when there is confounding by a categorical variable.
Assessment of habitat change on bird diversity and bird–habitat network of a Coral Island, South China Sea
Authors: Li Yingcan , Chen Zhiwen , Peng Chao , Huang Guangchuan , Niu Hongyu , Zhang Hongmao
Published: July 2021

Background

Understanding how island ecosystems change across habitats is a major challenge in ecological conservation under the conditions of habitat degradation. According to a 2-year investigation on Dong Island of the Paracel Islands, South China Sea, we assessed the roles of different habitats at the species level and community level of birds using topological and network analysis.

Results

In addition to the thousands of Sula sula (a large-sized arboreal seabird) inhabiting the forests, there were 56 other bird species were recorded, representing 23 families and 12 orders, ranging in habitats of wetlands, forests, shrublands, grasslands, and/or beaches. The bird–habitat network had high nestedness, and bird species showed obvious clustering distribution. Integrated topological and network analysis showed that wetlands had a high contribution to species diversity and network structure, and it was a cluster center of migrant birds. Forests and grasslands were species hub and connector respectively, and forests were also the key habitat for residents. Beaches and shrublands were peripherals. The loss of wetlands and forests will result in a sharp reduction of species richness, and even make the S. sula, and most of the resident birds, become locally extinct.

Conclusions

These results suggest that the wetland and forest habitats on the focal island are key important for migrant birds and resident birds respectively, and therefore much more attention should be paid to conservation of the focal island ecosystems.
Transcriptome analysis of five ovarian stages reveals gonad maturation in female Macrobrachium nipponense
Authors: Zhang Yuning , Jiang Sufei , Qiao Hui , Xiong Yiwei , Fu Hongtuo , Zhang Wenyi , Gong Yongsheng , Jin Shubo , Wu Yan
Published: July 2021

Background

Macrobrachium nipponense is an economically important species of freshwater shrimp in China. Unlike other marine shrimps, the ovaries in adult female M. nipponense can mature rapidly and periodically during the reproductive period, but the resulting high stocking densities and environmental deterioration can negatively impact the harvest yield and economic benefits. To better understand ovary development in female M. nipponense, we performed systematic transcriptome sequencing of five different stages of ovarian maturation.

Results

We obtained 255,966 Gb of high quality transcriptome data from 15 samples. Of the 105,082 unigenes that were selected, 30,878 were successfully annotated. From these unigenes, we identified 17 differentially expressed genes and identified three distinct gene expression patterns related to different biological processes. We found that cathepins, legumains, and cystatin were enriched in the lysosome pathway, and they are related to vitellogenin hydrolysis. Additionally, we found that myosin heavy chain 67 participated in oocyte excretion.

Conclusions

We provide the first detailed transcriptome data relating to the ovarian maturation cycle in M. nipponense. Our results provide important reference information about the genomics, molecular biology, physiology, and population genetics of M. nipponense and other crustaceans. It is conducive to further solve the problem of M. nipponense rapid ovarian maturation from the aspects of energy supply and cell division.
Genome-wide identification, expression analysis, and functional study of the GRAS transcription factor family and its response to abiotic stress in sorghum [Sorghum bicolor (L.) Moench]
Authors: Fan Yu , Yan Jun , Lai Dili , Yang Hao , Xue Guoxing , He Ailing , Guo Tianrong , Chen Long , Cheng Xiao-bin , Xiang Da-bing , Ruan Jingjun , Cheng Jianping
Published: July 2021

Background

GRAS, an important family of transcription factors, have played pivotal roles in regulating numerous intriguing biological processes in plant development and abiotic stress responses. Since the sequencing of the sorghum genome, a plethora of genetic studies were mainly focused on the genomic information. The indepth identification or genome-wide analysis of GRAS family genes, especially in Sorghum bicolor, have rarely been studied.

Results

A total of 81 SbGRAS genes were identified based on the S. bicolor genome. They were named SbGRAS01 to SbGRAS81 and grouped into 13 subfamilies (LISCL, DLT, OS19, SCL4/7, PAT1, SHR, SCL3, HAM-1, SCR, DELLA, HAM-2, LAS and OS4). SbGRAS genes are not evenly distributed on the chromosomes. According to the results of the gene and motif composition, SbGRAS members located in the same group contained analogous intron/exon and motif organizations. We found that the contribution of tandem repeats to the increase in sorghum GRAS members was slightly greater than that of fragment repeats. By quantitative (q) RT-PCR, the expression of 13 SbGRAS members in different plant tissues and in plants exposed to six abiotic stresses at the seedling stage were quantified. We further investigated the relationship between DELLA genes, GAs and grain development in S. bicolor. The paclobutrazol treatment significantly increased grain weight, and affected the expression levels of all DELLA subfamily genes. SbGRAS03 is the most sensitive to paclobutrazol treatment, but also has a high response to abiotic stresses.

Conclusions

Collectively, SbGRAs play an important role in plant development and response to abiotic stress. This systematic analysis lays the foundation for further study of the functional characteristics of GRAS genes of S. bicolor.
Diversity and prevalence of ANTAR RNAs across actinobacteria
Authors: Mehta Dolly , Ramesh Arati
Published: July 2021

Background

Computational approaches are often used to predict regulatory RNAs in bacteria, but their success is limited to RNAs that are highly conserved across phyla, in sequence and structure. The ANTAR regulatory system consists of a family of RNAs (the ANTAR-target RNAs) that selectively recruit ANTAR proteins. This protein-RNA complex together regulates genes at the level of translation or transcriptional elongation. Despite the widespread distribution of ANTAR proteins in bacteria, their target RNAs haven’t been identified in certain bacterial phyla such as actinobacteria.

Results

Here, by using a computational search model that is tuned to actinobacterial genomes, we comprehensively identify ANTAR-target RNAs in actinobacteria. These RNA motifs lie in select transcripts, often overlapping with the ribosome binding site or start codon, to regulate translation. Transcripts harboring ANTAR-target RNAs majorly encode proteins involved in the transport and metabolism of cellular metabolites like sugars, amino acids and ions; or encode transcription factors that in turn regulate diverse genes.

Conclusion

In this report, we substantially diversify and expand the family of ANTAR RNAs across bacteria. These findings now provide a starting point to investigate the actinobacterial processes that are regulated by ANTAR.
Integration of transcriptomic data identifies key hallmark genes in hypertrophic cardiomyopathy
Authors: Xu Jing , Liu Xiangdong , Dai Qiming
Published: July 2021

Background

Hypertrophic cardiomyopathy (HCM) represents one of the most common inherited heart diseases. To identify key molecules involved in the development of HCM, gene expression patterns of the heart tissue samples in HCM patients from multiple microarray and RNA-seq platforms were investigated.

Methods

The significant genes were obtained through the intersection of two gene sets, corresponding to the identified differentially expressed genes (DEGs) within the microarray data and within the RNA-Seq data. Those genes were further ranked using minimum-Redundancy Maximum-Relevance feature selection algorithm. Moreover, the genes were assessed by three different machine learning methods for classification, including support vector machines, random forest and k-Nearest Neighbor.

Results

Outstanding results were achieved by taking exclusively the top eight genes of the ranking into consideration. Since the eight genes were identified as candidate HCM hallmark genes, the interactions between them and known HCM disease genes were explored through the protein–protein interaction (PPI) network. Most candidate HCM hallmark genes were found to have direct or indirect interactions with known HCM diseases genes in the PPI network, particularly the hub genes JAK2 and GADD45A.

Conclusions

This study highlights the transcriptomic data integration, in combination with machine learning methods, in providing insight into the key hallmark genes in the genetic etiology of HCM.
Cost effectiveness of therapist delivered cognitive behavioural therapy and web-based self-management in irritable bowel syndrome: the ACTIB randomised trial
Authors: McCrone Paul , Everitt Hazel , Landau Sabine , Little Paul , Bishop Felicity L. , O’Reilly Gilly , Sibelli Alice , Holland Rachel , Hughes Stephanie , Windgassen Sula , Goldsmith Kim , Coleman Nicholas , Logan Robert , Chalder Trudie , Moss-Morris Rona
Published: July 2021

Background

Telephone therapist delivered CBT (TCBT) and web-based CBT (WCBT) have been shown to be significantly more clinically effective than treatment as usual (TAU) at reducing IBS symptom severity and impact at 12 months in adults with refractory IBS. In this paper we assess the cost-effectiveness of the interventions.

Methods

Participants were recruited from 74 general practices and three gastroenterology centres in England. Interventions costs were calculated, and other service use and lost employment measured and costed for one-year post randomisation. Quality-adjusted life years (QALYs) were combined with costs to determine cost-effectiveness of TCBT and WCBT compared to TAU.

Results

TCBT cost £956 more than TAU (95% CI, £601–£1435) and generated 0.0429 more QALYs. WCBT cost £224 more than TAU (95% CI, − £11 to £448) and produced 0.029 more QALYs. Compared to TAU, TCBT had an incremental cost per QALY of £22,284 while the figure for WCBT was £7724. After multiple imputation these ratios increased to £27,436 and £17,388 respectively. Including lost employment and informal care, TCBT had costs that were on average £866 lower than TAU (95% CI, − £1133 to £2957), and WCBT had costs that were £1028 lower than TAU (95% CI, − £448 to £2580).

Conclusions

TCBT and WCBT resulted in more QALYs and higher costs than TAU. Complete case analysis suggests both therapies are cost-effective from a healthcare perspective. Imputation for missing data reduces cost-effectiveness but WCTB remained cost-effective. If the reduced societal costs are included both interventions are likely to be more cost-effective.

Trial registration ISRCTN44427879 (registered 18.11.13).
Ticking on Pandora’s box: a prospective case-control study into ‘other’ tick-borne diseases
Authors: Hoornstra D. , Harms M. G. , Gauw S. A. , Wagemakers A. , Azagi T. , Kremer K. , Sprong H. , van den Wijngaard C. C. , Hovius J. W.
Published: July 2021

Background

Tick-borne pathogens other than Borrelia burgdorferi sensu lato – the causative agent of Lyme borreliosis – are common in Ixodes ricinus ticks. How often these pathogens cause human disease is unknown. In addition, diagnostic tools to identify such diseases are lacking or reserved to research laboratories. To elucidate their prevalence and disease burden, the study ‘Ticking on Pandora’s Box’ has been initiated, a collaborative effort between Amsterdam University Medical Center and the National Institute for Public Health and the Environment.

Methods

The study investigates how often the tick-borne pathogens Anaplasma phagocytophilum, Babesia species, Borrelia miyamotoi, Neoehrlichia mikurensis, spotted fever group Rickettsia species and/or tick-borne encephalitis virus cause an acute febrile illness after tick-bite. We aim to determine the impact and severity of these tick-borne diseases in the Netherlands by measuring their prevalence and describing their clinical picture and course of disease.

The study is designed as a prospective case-control study. We aim to include 150 cases – individuals clinically suspected of a tick-borne disease – and 3 matched healthy control groups of 200 persons each. The controls consist respectively of a group of individuals with either a tick-bite without complaints, the general population and of healthy blood donors. During a one-year follow-up we will acquire blood, urine and skin biopsy samples and ticks at baseline, 4 and 12 weeks. Additionally, participants answer modified versions of validated questionnaires to assess self-reported symptoms, among which the SF-36, on a 3 monthly basis.

Discussion

This article describes the background and design of the study protocol of ‘Ticking on Pandora’s Box’. With our study we hope to provide insight into the prevalence, clinical presentation and disease burden of the tick-borne diseases anaplasmosis, babesiosis, B. miyamotoi disease, neoehrlichiosis, rickettsiosis and tick-borne encephalitis and to assist in test development as well as provide recommendations for national guidelines.

Trial registration

NL9258 (retrospectively registered at Netherlands Trial Register, trialregister.nl in in February 2021).
Utility of interferon gamma/tumor necrosis factor alpha FluoroSpot assay in differentiation between active tuberculosis and latent tuberculosis infection: a pilot study
Authors: Zhang Lifan , Wan Shijun , Zhou Ziyue , Zhang Yueqiu , Liu Xiaoqing
Published: July 2021

Background

The differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging in clinical practice. We aimed to evaluate the diagnostic accuracy of the IFN-γ/TNF-α FluoroSpot assay for differentiating ATB from LTBI.

Methods

We conducted a pilot study of case-control design, using the FluoroSpot assay to simultaneously detect IFN-γ and TNF-α secretion at the single-cell level. The frequencies of antigen-specific single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells were detected. The optimal cutoffs value of frequencies for differentiating ATB from LTBI were determined according to receiver operating characteristic curve analysis. The sensitivity, specificity, predictive values (PV) and likelihood ratios (LR) of the FluoroSpot assay were calculated.

Results

Thirty patients diagnosed microbiologically with ATB, 36 healthcare workers with LTBI and 36 healthy controls were enrolled. After stimulated by ESAT-6 or CFP-10 peptides, the median frequencies of single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells in ATB patients were all significantly higher than those in LTBI and HC groups (P < 0.01). The frequencies of total IFN-γ-secreting T cells detected by FluoroSpot assay correlated significantly with those of T-SPOT.TB (r = 0.910 for ESAT-6, P < 0.001, r = 0.845 for CFP-10, P < 0.001). After stimulated by ESAT-6 peptides, with total TNF-α-secreting T cells frequencies at a cut off value of 21 iSFCs/250,000 PBMCs, the sensitivity, specificity, PLR, NLR, PPV, NPV of IFN-γ/TNF-α FluoroSpot assay in differentiating ATB from LTBI were 96.7% (95%CI, 82.8–99.9%), 94.3% (95%CI, 80.8–99.3%), 16.92 (95%CI, 4.40–65.08), 0.04 (95%CI, 0.01–0.24), 93.6% (95%CI,78.6–99.2%) and 97.1% (95%CI, 84.7–99.9%), respectively. With the frequencies of total TNF-α- and total IFN-γ-secreting T cells stimulated by ESAT-6 peptides combined, the specificity was increased to 97.1%, and the positive likelihood ratio to 31.5. The combination with CFP-10 might not improve the diagnostic accuracy of the ESAT-6 for differentiating ATB from LTBI.

Conclusions

IFN-γ/TNF-α FluoroSpot assay might have potential to help differentiate ATB from LTBI, but the findings need to be further verified by cross-sectional or prospective cohort studies.
Complement activation and blockade in massive post-partum haemorrhage, thrombotic microangiopathy and acute kidney injury: a case report
Authors: Guzzo G. , Kissling S. , Pantaleo G. , Pascual M. , Sadallah S. , Teta D.
Published: July 2021

Background

Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown.

Case presentation

A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation.

Conclusions

We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.
Recurrent membranous nephropathy with a possible alteration in the etiology: a case report
Authors: Matsumoto Ayumi , Matsui Isao , Mano Keiji , Mizuno Hitoshi , Katsuma Yusuke , Yasuda Seiichi , Shimada Karin , Inoue Kazunori , Oki Takashi , Hanai Tadashi , Kojima Keiko , Kaneko Tetsuya , Isaka Yoshitaka
Published: July 2021

Background

Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major pathogenic antigens for membranous nephropathy (MN). It has been reported that THSD7A-associated MN has a higher prevalence of comorbid malignancy than PLA2R1-associated MN. Here we present a case of MN whose etiology might change from idiopathic to malignancy-associated MN during the patient’s clinical course.

Case presentation

A 68-year-old man with nephrotic syndrome was diagnosed with MN by renal biopsy. Immunohistochemistry showed that the kidney specimen was negative for THSD7A. The first course of corticosteroid therapy achieved partial remission; however, nephrotic syndrome recurred 1 year later. Two years later, his abdominal echography revealed a urinary bladder tumor, but he did not wish to undergo additional diagnostic examinations. Because his proteinuria increased consecutively, corticosteroid therapy was resumed, but it failed to achieve remission. Another kidney biopsy was performed and revealed MN with positive staining for THSD7A. PLA2R1 staining levels were negative for both first and second biopsies. Because his bladder tumor had gradually enlarged, he agreed to undergo bladder tumor resection. Pathological examination indicated that the tumor was THDS7A-positive bladder cancer. Subsequently, his proteinuria decreased and remained in remission.

Conclusions

This case suggests that the etiology of MN might be altered during the therapeutic course. Intensive screening for malignancy may be preferable in patients with unexpected recurrence of proteinuria and/or change in therapy response.