bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective view of pediatric cases infected with SARS-CoV-2 of a middle-sized city in mainland China
Authors: Kang Yanjun , You Zhong , Wang Kang , Dong Zijuan , Zhang Jiajia , Qiu Yuanwang , Ge Guizhi
Published: December 2020

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 had resulted in a global pandemic. A comprehensive analysis of pediatric COVID-19 cases is essential to decipher the natural features of children under the risk of this disease.

In the epidemic period, all the children infected with SARS-CoV-2 in Wuxi, a city with a stable medical system during the COVID-19 outbreak in China, were enrolled for comprehensive data documenting their clinical, prognosis, follow-up, treatment and various tests results. Combing their family cluster characteristics, the epidemiological, hospitalization, and transmission features of children with SARS-CoV-2 were analyzed and discussed.

A total of 7 children were enrolled, including 4 mild cases, 1 moderate case, and 2 asymptomatic cases. The common symptoms were fever and dry cough. The length of viral nucleic acid duration in nasopharynx varied and was irrelevant to the severity of the symptom, whether symptomatic or asymptomatic. Two cases showed viral nucleic acid positive recurrence after discharge from the hospital. A child with type 1 diabetes was also focused, for the elevated blood sugar during hospitalization. All these children had close contacts with their family members, some of those were confirmed COVID-19 cases.

We provided a holistic and detailed portrayal of the pediatric COVID-19 cases in a typical city of timely response to the epidemic. While the family cluster exhibits the major transmission mode, attention should be paid for the potential risk since the expanded social space of children in future.
The associated factors for spontaneous intranodular hemorrhage of partially cystic thyroid nodules
Authors: Yang Haizhen , Zhao Shuangshuang , Zhang Zheng , Chen Yanwei , Wang Keke , Shang Mengyuan , Chen Baoding
Published: December 2020

Spontaneous intranodular hemorrhaging in benign partially cystic thyroid nodules was reported to cause neck swelling, difficulty swallowing, and other oppressive symptoms attributed to their growing progressively at high rates. In our study, the risk factors for hemorrhaging in these nodules were investigated.

We retrospectively analyzed benign partial cystic thyroid nodules from September 2017 to December 2019, and divided them into 2 groups according to the occurrence of intranodular hemorrhage. Age, gender, follow-up time nodules initial maximum diameter, blood supply, spongiform content, nodules solid components, and internal solid portion were compared between the 2 groups at the first ultrasound examination. Chi-Squared and multivariate analysis were performed to evaluate the association of hemorrhage with clinical and ultrasonographic characteristics. ROC analysis was performed to evaluate the utility of factors in predicting hemorrhage.

There were 59 occurrences of intranodular hemorrhage, which were associated with abundant blood supply, spongiform contents, and unsmooth margin of the internal solid portion. After multivariate analysis, abundant blood supply, and spongiform content were independent predictors for hemorrhage. In ROC analysis integrating these predictors, the sensitivity was 62.7% and specificity was 95.2% with the AUC 0.881.

Partially cystic thyroid nodules with abundant blood supply, non-smooth margin of the internal solid portion and a spongiform internal content were apt to spontaneous intranodular hemorrhaging, which can be recognized as soon as possible by ultrasound.
Efficacy and safety of Tian moxibustion in treating allergic rhinitis
Authors: Deng Gen , Wan Qun , Wang Jinlong , Ye Wenguo
Published: December 2020

Background:

Allergic rhinitis, abbreviated AR, modern medicine considers AR to be a chronic inflammatory reactive disease of the nasal mucosa mediated by exposure to allergens such as pollen and mites immunoglobulin E. AR not only affects patients’ daily life, sleep, work, and study, but also brings huge economic burden to patients and society. At present, desensitization therapy, antiallergic drugs, antihistamines, hormones, and other drugs are used to improve symptoms or immune regulation, but the clinical short-term and long-term efficacy is general, the symptoms are easy to be repeated after drug withdrawal, and the long-term toxicity and side effects of drugs are obviously insufficient. Tian moxibustion therapy has a good effect on AR. Therefore, this paper will carry out a systematic evaluation and meta-analysis of the efficacy and safety of moxibustion in the treatment of allergic rhinitis.

Methods:

Eight electronic databases will be searched, including PubMed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database (WF), and Chinese Biomedical Literature Database (CBM). We will search above electronic databases from the beginning to November 2020, without any language restriction, but involving only the human subjects. Clinical efficacy, including total effective rate or cure rate, and recurrence rate will be accepted as the primary outcomes. The Rhinoconjunctivitis quality of life questionaire (RQLQ) score, symptom score (nasal congestion, snot, continuous sneezing) will be used as secondary outcomes. The Cochrane Handbook of Systematic Review (5.3.0) randomized controlled trials (RCT) risk assessment tool will be used to evaluate the risk of bias by 2 independent researchers.

Results:

After the completion of this study, the results will be reported, so it is not possible to give accurate results at present.

Conclusions:

The results of this study will provide reliable evidence for the efficacy and safety of Tian moxibustion in the treatment of allergic rhinitis.

Ethics and dissemination:

This paper does not need to be approved by the Ethics Committee, because this paper is a systematic review and quality evaluation of relevant literature. The results of this study will be disseminated in the form of a paper to help better guide the clinical practice of Tian moxibustion in the treatment of allergic rhinitis.

INPLASY Registration number:

INPLASY2020110058.
Nutritional consequences of bariatric surgery – prevention, detection and management
Authors: O’Kane Mary
Published: December 2020

Purpose of review

Bariatric surgery is an effective treatment option for severe and complex obesity; however, those who undergo such surgery need access to nutritional monitoring and vitamin and mineral supplementation to avoid the development of nutritional deficiencies.

Recent findings

The British Obesity and Metabolic Surgery Society and the American Society for Metabolic and Bariatric Surgery have recently updated their recommendations on preoperative and postoperative nutritional monitoring and supplementation. There is a growing interest in the more malabsorptive procedures that are associated with an increased risk of nutritional deficiencies. Nutritional monitoring and prevention of nutritional deficiencies are discussed.

Long-term follow-up that includes annual nutritional monitoring and access to a dietetic annual review is recommended; however, in the United Kingdom, many bariatric surgery centres are only commissioned to provide 2 years of follow-up, after which care is transferred to the general practitioner. Consideration should be given to developing shared care models for aftercare and also for the aftercare of malabsorptive procedures to remain with specialist centres.

Bariatric surgery is a safe and effective treatment option for severe and complex obesity. It is essential that patients have access to lifelong nutritional monitoring adjustment of vitamin and mineral supplements to prevent nutritional issues.
Effect of Clinical Reasoning Seminars on Medical-Surgical Specialty HESI Examination Scores
Authors: Fugate Stephanie , Hampton Debra , Ashford Kristin , Welsh Darlene , Marfell Julie
Published: December 2020

Background

Clinical reasoning and clinical judgment have been identified as essential skills for the delivery of quality patient care.

Purpose

The purpose of this study was to determine the impact of clinical reasoning seminars (CRSs) on medical-surgical specialty HESI examination scores of high-risk students.

Methods

A retrospective correlational design was used for this study, which involved a review of medical-surgical HESI scores for 115 junior-level baccalaureate nursing students who were identified as academically high-risk and who participated in a series of CRSs.

Results

The participation in CRSs by high-risk students did not have a statistically significant impact on the medical-surgical HESI scores. Students who attended CRSs, however, had a higher mean medical-surgical HESI score than students who did not attend any CRSs.

Conclusion

Although statistical differences were not found, it appears that high-risk students may have benefitted from participation in CRSs.
Clinical Decision Support Using a Partially Instantiated Probabilistic Graphical Model Optimized through Quantum Annealing: Proof-of-Concept of a Computational Method Using a Clinical Data Set
Authors: Sahner David K. , Williams Richard J.
Published: December 2020

An approach is described to building a clinical decision support tool which leverages a partially instantiated graphical model optimized through quantum annealing. Potential advantages of such a strategy include the practical, and potentially real-time, use of multidimensional patient data to make a host of intuitively understandable predictions and recommendations in complex cases which are informed by a data-driven probabilistic model. Preliminary proof-of-concept of the general approach is demonstrated using a large well-established anonymized patient data set, revealing the predictive capability of a specific model. Ideas for future research are discussed.
Hepatitis C Virus Drugs Simeprevir and Grazoprevir Synergize with Remdesivir to Suppress SARS-CoV-2 Replication in Cell Culture
Authors: Bafna Khushboo , White Kris , Harish Balasubramanian , Rosales Romel , Ramelot Theresa A. , Acton Thomas B. , Moreno Elena , Kehrer Thomas , Miorin Lisa , Royer Catherine A. , García-Sastre Adolfo , Krug Robert M. , Montelione Gaetano T.
Published: December 2020

Effective control of COVID-19 requires antivirals directed against SARS-CoV-2 virus. Here we assess ten available HCV protease inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity of the substrate binding clefts of SARS- CoV-2 Mproand HCV NS3/4A proteases, and virtual docking experiments show that all ten HCV drugs can potentially bind into the Mprobinding cleft. Seven of these HCV drugs inhibit SARS-CoV-2 Mproprotease activity, while four dock well into the PLprosubstrate binding cleft and inhibit PLproprotease activity. These same seven HCV drugs inhibit SARS-CoV-2 virus replication in Vero and/or human cells, demonstrating that HCV drugs that inhibit Mpro, or both Mproand PLpro, suppress virus replication. Two HCV drugs, simeprevir and grazoprevir synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, thereby increasing remdesivir inhibitory activity as much as 10-fold.

Highlights

Several HCV protease inhibitors are predicted to inhibit SARS-CoV-2 Mproand PLpro.

Seven HCV drugs inhibit Mproenzyme activity, four HCV drugs inhibit PLpro.

Seven HCV drugs inhibit SARS-CoV-2 replication in Vero and/or human cells.

HCV drugs simeprevir and grazoprevir synergize with remdesivir to inhibit SARS- CoV-2.

eTOC blurb

Bafna, White and colleagues report that several available hepatitis C virus drugs inhibit the SARS-CoV-2 Mproand/or PLproproteases and SARS-CoV-2 replication in cell culture. Two drugs, simeprevir and grazoprevir, synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, increasing remdesivir antiviral activity as much as 10-fold.

Abstract Figure
A GPCR negative feedback loop underlies efficient coding of external stimuli
Authors: Ruach Rotem , Yellinek Shai , Itskovits Eyal , Zaslaver Alon
Published: December 2020

Efficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatio-temporal patterns and with orders of magnitude varying intensities. Nevertheless, sensory neurons accurately extract the relevant information from such perplexing signals. Here, we show how a single sensory neuron inC. elegansworms can cell-autonomously encode complex stimulus patterns composed of instantaneous sharp changes and of slowly-changing continuous gradients. This encoding relies on a simple negative feedback in the GPCR signaling pathway in which TAX-6/Calcineurin plays a key role in mediating the feedback inhibition. Crucially, this negative feedback pathway supports several important coding features that underlie an efficient navigation strategy, including exact adaptation and adaptation to the magnitude of the gradient’s first derivative. A simple mathematical model accurately captured the fine neural dynamics of both wt andtax-6mutant animals, further highlighting how the calcium-dependent activity of TAX-6/Calcineurin dictates GPCR inhibition and response dynamics. As GPCRs are ubiquitously expressed in all sensory neurons, this mechanism may be a universal solution for efficient cell-autonomous coding of external stimuli.
Chromatin remodelerArid1aregulates subplate neuron identity and wiring of cortical connectivity
Authors: Doyle Daniel Z. , Lam Mandy M. , Qalieh Adel , Qalieh Yaman , Sorel Alice , Funk Owen H. , Kwan Kenneth Y.
Published: December 2020

Loss-of-function mutations in chromatin remodeler geneARID1Aare a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterizeArid1afunction during cortical development and find unexpectedly selective roles forArid1ain subplate neurons. Subplate neurons (SPNs), strategically positioned at the interface of cortical grey and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pan-cortical deletion ofArid1aleads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. SparseArid1adeletion, however, does not autonomously misroute callosal axons, implicating non-cell autonomousArid1afunctions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by corticalArid1adeletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression followingArid1adeletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate-thalamocortical axon co-fasciculation (“handshake”), and extracellular matrix, are severely disrupted. To empirically testArid1asufficiency in subplate, we generate a cortical plate deletion ofArid1athat spares SPNs. In this model, subplateArid1aexpression is sufficient for subplate-thalamocortical axon co-fasciculation and extracellular matrix assembly. Consistent with these wiring functions, subplateArid1asufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus,Arid1ais a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.

Significance

The cognitive, perceptive, and motor capabilities of the mammalian cerebral cortex depend on assembly of circuit connectivity during development. Subplate neurons, strategically located at the junction of grey and white matter, orchestrate the wiring of cortical circuits. Using a new approach to study gene necessity and sufficiency in subplate neurons, we uncover an essential role for chromatin remodelerArid1ain subplate neuron gene expression and axon guidance functions. Cortical deletion ofArid1adisrupts subplate-dependent formation of corpus callosum, targeting of thalamocortical axons, and development of sensory maps. Together, our study identifiesArid1aas a central regulator of subplate-dependent axon pathfinding, establishes subplate function as essential to callosum development, and highlights non-cell autonomous mechanisms in neural circuit formation and disorders thereof.
Microbe-seq: high-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome
Authors: Zheng Wenshan , Zhao Shijie , Yin Yehang , Zhang Huidan , Needham David M. , Evans Ethan D. , Dai Chengzhen L. , Lu Peter J. , Alm Eric J. , Weitz David A.
Published: December 2020

We presentMicrobe-seq, a high-throughput single-microbe method that yields strain-resolved genomes from complex microbial communities. We encapsulate individual microbes into droplets with microfluidics and liberate their DNA, which we amplify, tag with droplet-specific barcodes, and sequence. We useMicrobe-seqto explore the human gut microbiome; we collect stool samples from a single individual, sequence over 20,000 microbes, and reconstruct nearly-complete genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe genomic signatures of microbial interactions: we reconstruct the horizontal gene transfer (HGT) network within the individual and observe far greater exchange within the same bacterial phylum than between different phyla. We probe bacteria-virus interactions; unexpectedly, we identify a significantin vivoassociation between crAssphage, an abundant bacteriophage, and a single strain ofBacteroides vulgatus. Microbe-seqcontributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.
Primary restriction of S-RNase cytotoxicity by a stepwise ubiquitination and degradation pathway inPetunia hybrida
Authors: Zhao Hong , Song Yanzhai , Li Junhui , Zhang Yue , Huang Huaqiu , Li Qun , Zhang Yu’e , Xue Yongbiao
Published: December 2020

In self-incompatible Solanaceous species, the pistil S-RNase acts as cytotoxin to inhibit self-pollination but is polyubiquitinated by the pollen-specific non-selfS-locus F-box (SLF) proteins and subsequently degraded by the ubiquitin-proteasome system (UPS), allowing cross-pollination. However, it remains unclear how S-RNase is restricted by the UPS. Here, we first show thatPetunia hybrida(Ph) S3-RNase is largely ubiquitinated by K48-linked polyubiquitin chains at three regions, R I, II and III. R I is ubiquitinated in unpollinated, self- and cross-pollinated pistils, indicating its occurrence prior to PhS3-RNase uptake into pollen tubes, whereas R II and III are exclusively ubiquitinated in cross-pollinated pistils. Second, removal of R II ubiquitination resulted in significantly reduced seed sets from cross-pollination and that of R I and III in less extents, indicating their increased cytotoxicity. In consistent, the mutated R II of PhS3-RNase resulted in marked reduction of its degradation, whereas that of R I and III in less reductions. Taken together, our results demonstrate that PhS3-RNase R II functions as a major ubiquitination region for its destruction and R I and III as minor ones, revealing that its cytotoxicity is primarily restricted by a stepwise UPS mechanism for cross-pollination inP. hybrida.

ONE SENTENCE SUMMARY

Biochemical and transgenic analyses reveal thatPetunia hybridaS3-RNase cytotoxicity is largely restricted by a stepwise ubiquitination and degradation pathway during cross-pollination.
Transcriptional responses to arbuscular mycorrhizal symbiosis development are conserved in the early divergentMarchantia paleacea
Authors: Sgroi Mara , Paszkowski Uta
Published: December 2020

Arbuscular mycorrhizal symbiosis (AMS) arose in land plants more than 400 million years ago, perhaps acting as a major contributor to plant terrestrialization. The ability to engage in AMS is evolutionarily conserved across most clades of extant land plants, including early diverging bryophytes. Despite its broad taxonomic distribution, little is known about the molecular components that underpin AMS in early diverging land plants as the mechanisms regulating the symbiosis were primarily characterized in angiosperms. Several AMS associated genes were recently shown to be conserved in liverworts and hornworts, but evidence of them being associated with symbiosis in bryophytes is scarce. In this study, we characterised the dynamic response of the liverwortMarchantia paleaceatoRhizophagus irregulariscolonization by time-resolved transcriptomics across progressive stages of symbiosis development. Gene orthology inference and comparative analysis of theM. paleaceatranscriptional profile with a well characterised legume model -Medicago truncatula- revealed a deep conservation of transcriptional responses to AMS across distantly related species. We identified evolutionarily conserved patterns of expression of genes required for pre-symbiotic signalling, intracellular colonization and symbiotic nutrient exchange. Our study demonstrates that the genetic machinery regulating key aspects of symbiosis in plant hosts is largely conserved and coregulated across distantly related land plants. If bryophytes are confirmed to be monophyletic, our analysis provides novel insights on the first molecular pathways associated with symbiosis at the dawn of plant colonization of land.

Significance Statement

Arbuscular mycorrhizal symbiosis (AMS) between plants and soil fungi was proposed as one of the key adaptations enabling land colonization by plants. The symbiosis is widespread across most extant plant clades, including early-diverging bryophytes, suggesting that it evolved before the last common ancestor of land plants. Recent phylogenetic analyses uncovered that genes regulating AMS in angiosperms are present in the genomes of bryophytes. Our work shows that a set of these genes are transcriptionally induced during AMS in liverworts. Based on the conservation of their transcriptional profiles across land plants, we propose that these genes acquired an AMS-associated function before the last common ancestor of land plants.
Expression of macromolecular organic nitrogen degrading enzymes identifies potential mediators of soil organic N availability to an annual grass
Authors: Sieradzki Ella T. , Nuccio Erin E. , Pett-Ridge Jennifer , Firestone Mary K.
Published: December 2020

Nitrogen (N) commonly limits terrestrial plant growth partly because most soil-N is present as macromolecular organic compounds and not directly available to plants. Soil microbes degrade these large N-containing substrates to gradually release plant-available inorganic-N throughout the growing season, potentially meeting plant demand. Knowing which microbes are responsible for release of organic N, as well as their spatiotemporal patterns of activity, can enable microbial management strategies that increase plant access to soil-N and reduce dependency on fertilizer-N. We used time-resolved metatranscriptomes to follow taxonomy-resolved differential expression of N-depolymerizing enzymes.

Taxonomic groups show adaptations based on extracellular proteases to specialized habitats in soil characterized by presence (Betaproteobacteria) or absence (Thaumarcheota) of live roots and root detritus (Deltaproteobacteria and Fungi). A similar increase of eukaryotic chitinases near root detritus hints at predation of fungi. Others demonstrate temporal patterns such as increasing expression over time, implying increased competitiveness with substrate depletion (Chloroflexi). Phylotypes from the same genus can have different potential benefits to the plant based on protease expression (e.g., Janthinobacterium), which should be considered when designing bioaugmentation. We identify one Janthinobacterium phylotype and two Burkholderiales that may be candidates for bioaugmentation near young roots and a Rhizobacter which could benefit mature roots.
Maladaptive oxidative stress cascade drives type I interferon hyperactivity in TNF activated macrophages promoting necrosis in murine tuberculosis granulomas
Authors: Brownhill Eric , Yabaji Shivraj M. , Zhernovkov Vadim , Rukhlenko Oleksii S. , Seidel Kerstin , Bhattacharya Bidisha , Chatterjee Sujoy , Chen Hui A. , Crossland Nicholas , Bishai William , Kholodenko Boris N. , Gimelbrant Alexander , Kobzik Lester , Kramnik Igor
Published: December 2020

Tuberculosis remains a critical infectious disease world-wide. The development of novel therapeutic strategies requires greater understanding of host factors that contribute to disease susceptibility. A major unknown in TB pathogenesis is the mechanism of necrosis in TB granulomas that leads to the massive lung tissue damage and cavity formation necessary for the pathogen transmission. In humans, TB progression has been linked to hyperactivity of type I IFN (IFN-I) pathway, the primary cause of which remains elusive.

We studied the mechanistic drivers of pulmonary TB progression using a unique model B6J.C3-Sst1C3HeB/FejKrmn mice that develop human-like necrotic TB granulomas and IFN-I hyperactivity. We established that IFNβ super-induction occurred in the susceptible macrophages in response to continuous TNF stimulation in the context of a dysregulated antioxidant defense. We observed that unresolving oxidative stress amplified the induction of IFNβ through JNK activation and induced the Integrated Stress Response via PKR activation as a compensatory pathway. Subsequently, PKR amplifies IFNβ upregulation, forming a positive feedback loop, maintaining the hyperinflammatory state in susceptible macrophages and leading to mitochondrial dysfunction. Thus, within the inflammatory milieu, a cell-intrinsic mechanism of chronic regulatory dysfunction and unresolved stress gradually weakens the macrophage and ultimately promotes the necrotization of TB granulomas. The aberrant macrophage response to TNF can be prevented by an iron chelator and inhibitor of lipid peroxidation, ferrostatin-1. Moreover, ferrostatin treatment increased macrophage survival and boosted bacterial control in the TNF-stimulated macrophages infected with virulent Mtb. These findings identify targets for host-directed therapeutics to interrupt necrotization in TB granulomas.
Predicting Success of Phase III Trials in Oncology
Authors: Hegge Stephan J , Thunecke Markus Erik , Krings Matthias , Ruedin Leonard , Mueller Jan Saputra , von Buenau Paul
Published: December 2020

We developed a model predicting the probability of success (PoS) for single planned or ongoing PhIII trials based on information available at trial initiation. Such a model is highly relevant for study sponsors to capture risk and opportunity on a trial to trial basis through trial optimization, and for investors to select drugs whose trial design match their investment strategy.
Objectives: To predict the outcome of planned or ongoing PhIII trials in oncology, given publicly available prior information
Design, Setting, Participants: Predictive modeling using publicly available data for 360 completed PhIII and 1240 PhII studies initiated between 2003 and 2012. Success and failure of PhIII studies were modeled using Bayesian logistic regression model.
Main Outcome Measures: Predicted PoS of individual PhIII trials based on a Bayesian model calibrated on publicly available data translated into 16 composite scores. Those scores cover aspects such as trial design, indication, number of patients, phase II (PhII) study outcomes, experience of sponsor at time of trial initiation, and others.
Results: The model allows to calculate the PoS distribution, including credible intervals, for a PhIII trial in oncology. The predictive performance was determined using an area under the receiver operator curve (AUROC), resulting in an overall performance of 73%oPP (mean AUROC). We identified two key factors contributing to the predictive performance of the model: quality and strength of PhII data and experience of the sponsor at the time of study initiation.
Conclusion and Relevance: We describe the generation and application of a statistical model predicting the PoS for individual PhIII trials in oncological indications with unprecedented predictive performance. Compared to other approaches, this is the first study generating a fully transparent model resulting in trial specific PoS distributions. Moreover, we have shown that qualitative concepts such as PhII knowledge or sponsor R&D strength can be captured in quantitative scores and that these scores have a high predictive power.
Social distancing and preventive practices of government employees in response to COVID-19 in Ethiopia
Authors: Deressa Wakgari , Worku Alemayehu , Abebe Workeabeba , Getachew Sefonias , Amogne Wondwosson
Published: December 2020

Background: Public health measures are critical to mitigate the spread of the novel coronavirus disease 2019 (COVID-19) pandemic. Ethiopia has implemented a variety of essential public health measures in response to the spread of the virus. This study aimed to assess social distancing and preventive practices of government employees in response to COVID-19.

Methods: A cross-sectional study was conducted among 1573 government employees selected from 46 public institutions (16 National, 18 from Addis Ababa City Administration, and 12 from Oromia Regional State) located in Addis Ababa. Data were collected from 8th to 19th June 2020 using a paper-based self-administered questionnaire and analyzed using SPSS version 23.0. ANOVA and t-tests were applied to assess the difference between groups. Bivariate and multivariable logistic regression analyses were used to identify factors associated with outcome variables.

Results: The majority of the participants reported wearing of facemask (96%), avoiding close contact with people including handshaking (94.5%), frequent had washing (94.1%), maintaining physical distancing (89.5%), avoiding mass gatherings (88.1%), and restricting movement and travelling (84.1%). More than 80% of the participants perceived that consistently wearing a facemask is highly effective in preventing the transmission of coronavirus. Participants from Oromia reported statistically significantly lower odds of perceived effectiveness of facemask in preventing coronavirus infection (adjusted OR=0.27, 95% CI:0.17-0.45). About 19% of the respondents reported that they had ever tested for COVID-19. Participants within the age groups of 18-29 were more likely to test for coronavirus than the older age groups. Whilst, respondents from Oromia were less likely to test for coronavirus than those from national level (adjusted OR=0.31, 95% CI:0.16-0.60). About one-third (31.3%) of the respondents strongly agreed that the policy responses that the Government had taken to contain the spread of coronavirus were reasonable, and 38.5% agreed with the policy responses.

Conclusions: The findings showed higher social distancing and preventive practices among the government employees in response to COVID-19. People should properly apply social distancing measures, wearing facemasks, and washing hands frequently with water and soap as a comprehensive package of SARS-CoV-2 prevention and control strategies. Rules and regulations imposed by the Government should be properly enforced in order to control the pandemic.
Parental administration of analgesia to children attending the emergency department with acutely painful conditions.
Authors: Daly Tessa Kathleen , O'Brien Rory , Murphy Adrian
Published: December 2020

Background
Acute paediatric pain management is often suboptimal in the emergency setting. There is a paucity of published literature on parental administration of analgesia to children, prior to their arrival at the emergency department (ED). The objective of this study was to describe the prevalence of pre-hospital analgesic administration by parents/guardians of children ≤16 years presenting to ED, with acutely painful conditions.

Methods
This was a prospective cross-sectional study conducted across two EDs in the South of Ireland with a collective annual attendance of approximately 100,000 patients. A consecutive sample of 400 parents/guardians of children aged between 6 months and 16 years, who were self-referred to ED with acutely painful conditions, were included. Data collected included patient demographics, pain score and analgesia administration. Data was analysed with SPSS software using descriptive and inferential statistics.

Results
189/400(47%) children received analgesia from their parents/guardians pre-ED arrival. Factors independently associated with increased parental administration of analgesia were: pain score ≥5/10 53.4%(95%CI 48%-59%) vs ≤4/10 29%(95%CI 21%-38%), children with siblings 49.7%(95%CI 45%-56%) vs without siblings 35.3%(95%CI 24%-47%) and presenting <48 hours from onset of pain 50.1%(95%CI 45%-55%) vs presenting ≥48 hours 30.5%(95%CI 19%-42%). Of the 400 participants, 211(53%) received no analgesia before attending ED. Reasons for parents not administering analgesia included: 62/211(29.4%) did not think the child needed it, 39/211(18.5%) accident did not happen at home, 34/211(16.1%) did not want to mask the presence of the pain, 20/211(9.5%) believed the hospital should give medications, and 18/211(8.5%) afraid it would be wrong/harmful.

Conclusions
Over half the children presenting to ED, with acutely painful conditions, did not receive adequate or timely pain relief pre-ED arrival, causing avoidable suffering. Parental misconceptions about acute pain management are major barrier to analgesic administration. Educational strategies are required to dispel misconceptions, which may ultimately improve the care for this population.
Genome-wide identification and comparative analysis ofDofgene family inBrassica napus
Authors: Lohani Neeta , Babaei Saeid , Singh Mohan B. , Bhalla Prem L.
Published: December 2020

DOF, DNA binding with one finger proteins are plant-specific transcription factors shown to play roles in diverse plant functions. However, a—little is known about DOF protein repertoire of the allopolyploid crop,Brassica napus. Here, we report genome-wide identification and systematic analysis of theDoftranscription factor family in this important oilseed crop. We identified 117Brassica napusDof genes (BnaDofs). So far, this is the largest number ofDofgenes reported in a single eudicot species. Based on phylogenetic analysis,BnaDofswere classified into nine groups (A, B1, B2. C1, C2.1, C2.2, C3, D1, D2). Most members belonging to a particular group displayed conserved gene structural organisation and similar protein motifs distribution. Chromosomal localisation analysis highlighted the uneven distribution ofBnaDofsacross all chromosomes. Evolutionary analysis exemplified that the divergence ofBrassicagenus from Arabidopsis, the whole genome triplication event, and the hybridisation ofB. oleraceaandB. rapato formB. napus, followed by gene loss and rearrangements, led to the expansion and divergence of Dof TF gene family inB. napus. Functional annotation of BnaDof proteins, cis-element analysis of their promoters suggested potential roles in organ development, the transition from vegetative to the reproductive stage, light responsiveness, phytohormone responsiveness as well as abiotic stress responses. Furthermore, the transcriptomic analysis highlighted the preferential tissue-specific expression patters ofBnaDofsand their role in response to various abiotic stress. Overall, this study provides a comprehensive understanding of the molecular structure, evolution, and potential functional roles ofDofgenes in plant development and abiotic stress response.
Longest Order Conserved Exemplar Subsequences
Authors: Zhang Shu , Pu Lianrong , Yang Runmin , Wang Luli , Zhu Daming , Jiang Haitao
Published: December 2020

We propose a new problem whose input data are two linear genomes together with two indexed gene subsequences of them, which asks to find a longest common exemplar subsequence of the two given genomes with a subsequence identical to the given indexed gene subsequences. We present an algorithm for this problem such that the algorithm is allowed to take diminishing time and space to solve the problem by setting the indexed genes with an incremental number. Although an incremental number of indexed genes were selected, the algorithm was verified definite to reach a solution whose length insistently comes very close to a real longest common exemplar subsequence of the two given genomes.

Aiming at 23 human/gorilla chromosome pairs, the algorithm was examined for use in questing for longest common exemplar subsequences whose basic units are annotated genes as well as pseudo genes, namely consecutive DNA subsequences. By contrasting the pseudo gene common exemplar subsequences the algorithm had reached for the human chromosomes 7 and 16 and their gorilla homologues with those annotated genes in the human and gorilla chromosomes, we found more than 1 000 and 500 pseudo genes in the human chromosomes 7 and 16 that occur in the same order as they are in the gorilla chromosomes 7 and 16 and, do not overlap with any annotated gene.

Author summary

There is a benefit of the algorithm: It can reach a long enough common exemplar subsequence of two linear genomes in as fast a speed as one requires even if the given genomes would be equipped with too many duplicated genes, which can be done by setting incremental number of indexed genes. We developed a Java software based on the algorithm, that has been available for download onhttps://github.com/ShuZhang-sdu/LCES.

Only in need to set the indexed gene sequences as null, was it verified successful for our algorithm to obtain the longest common exemplar subsequences of the annotated gene summary pairs extracted from 23 human/gorilla chromosome pairs.

In convenience for researchers to find new motifs or conserved genes, we devoted for the algorithm to quest pseudo gene (i.e. consecutive DNA subsequences) summary pairs of the 23 human/gorilla chromosome pairs for solutions. There are 20 pseudo gene summary pairs whose longest common exemplar subsequences have been found by the algorithm with null indexed gene sequences. The other 3 pseudo gene summary pairs were verified solvable for the algorithm to reach their longest common exemplar subsequences that have to admit subsequences identical to given indexed gene subsequences. There were informed to exist 2 353 and 1 148 pseudo genes in the gorilla chromosome 7 and 16 that occur in the same order as they are in the human chromosome 7 and 16 and, do not overlap with any annotated gene. These pseudo genes should be significant for annotating the human or gorilla genome.
The statistical challenge of finding spontaneous changes in functional connectivity in high-dimensional fMRI data
Authors: Vidaurre Diego
Published: December 2020

An important question in neuroscience is whether or not we can interpret spontaneous variations in the pattern of correlation between brain areas, which we refer to as functional connectivity or FC, as an index of dynamic neuronal communication in fMRI. That is, can we measure time-varying FC reliably? And, if so, can FC reflect information transfer between brain regions at relatively fast-time scales? Answering these questions in practice requires dealing with the statistical challenge of having high-dimensional data and a comparatively lower number of time points or volumes. A common strategy is to use PCA to reduce the dimensionality of the data, and then apply some model, such as the hidden Markov model (HMM) or a Bayesian mixture of distributions, to find a set of distinct FC patterns or states. The distinct spatial properties of these FC states together with the time-resolved switching between them offer a flexible description of time-varying FC. In this work, we show that in this context PCA can suffer from systematic biases and loss of sensitivity for the purposes of finding time-varying FC. To get around these issues, we propose a novel variety of the HMM, the HMM-PCA, where the states are themselves PCA decompositions. Since PCA is based on the data covariance, the state-specific PCA decompositions reflect distinct patterns of FC. We show, theoretically and empirically, that fusing dimensionality reduction and time-varying FC estimation in one single step can avoid these problems and outperform alternative approaches, eventually facilitating the quantification of transient communication in the brain.

Author summary

We show that PCA, although widely used in practice, can introduce important biases and loss of sensitivity in the estimation of time-varying functional connectivity on high-dimensional fMRI data. We discuss these limitations and propose a new method that, by performing dimensionality reduction and time-varying functional connectivity estimation in one single step, can effectively overcome these limitations.
powerEQTL: An R package and shiny application for sample size and power calculation of bulk tissue and single-cell eQTL analysis
Authors: Dong Xianjun , Li Xiaoqi , Chang Tzuu-Wang , Weiss Scott T. , Qiu Weiliang
Published: December 2020

Genome-wide association studies (GWAS) have revealed thousands of genetic loci for common diseases. One of the main challenges in the post-GWAS era is to understand the causality of the genetic variants. Expression quantitative trait locus (eQTL) analysis has been proven to be an effective way to address this question by examining the relationship between gene expression and genetic variation in a sufficiently powered cohort. However, it is often tricky to determine the sample size at which a variant with a specific allele frequency will be detected to associate with gene expression with sufficient power. This is particularly demanding with single-cell RNAseq studies. Therefore, a user-friendly tool to perform power analysis for eQTL at both bulk tissue and single-cell level will be critical. Here, we presented an R package called powerEQTL with flexible functions to calculate power, minimal sample size, or detectable minor allele frequency in both bulk tissue and single-cell eQTL analysis. A user-friendly, program-free web application is also provided, allowing customers to calculate and visualize the parameters interactively.

Availability and implementation

The powerEQTL R package source code and online tutorial are freely available at CRAN:https://cran.r-project.org/web/packages/powerEQTL/. The R shiny application is publicly hosted athttps://bwhbioinfo.shinyapps.io/powerEQTL/.

Contact

Xianjun Dong (xdong@rics.bwh.harvard.edu), Weiliang Qiu (weiliang.qiu@sanofi.com)

Supplementary information

Supplementary data are available at Bioinformatics online.
On-demand food delivery: investigating the economic performances
Authors: Seghezzi Arianna , Mangiaracina Riccardo
Published: December 2020

Purpose

This paper focusses on on-demand food delivery (ODFD), i.e. the delivery of freshly prepared meals to customers' homes, enabled by the use of online platforms. In ODFD, a key process is represented by last-mile deliveries (LMDs): they directly affect customers (the delivery price influences their purchase intention), riders (the compensation drives their willingness to perform deliveries) and platforms (deliveries are very expensive). In this context, this work aims to investigate the economic performances of ODFD LMDs.

Design/methodology/approach

This study adopts a multi-method threefold process. First, it develops a model that – after the generation of customers' demand and the assignment of deliveries to available riders – identifies incomes and costs faced by an ODFD operator. Second, the model is applied to a base case in Milan (Italy). Third, sensitivity analyses are performed (on daily demand and riders' salary).

Findings

The analyses allow – besides the identification of significant values associated to ODFD profitability – to draw general insights about delivery price (e.g. free delivery is not economically sustainable), daily demand (e.g. greater demand values do not only improve positive results but also worsen negative ones) and fixed/variable wage mix (e.g. increasing the variable wage enhances the profitability for platforms).

Originality/value

On the academic side, this word enhances extant literature about ODFD, proposing a model – with multidisciplinary implications – to strategically investigate profitability conditions of LMDs. On the managerial side, it provides support for (logistics/marketing) ODFD practitioners since it allows to evaluate the potential impact of significant decisions on profitability.
Hemodialysis‐related headache: Still a challenge in 2020? Effect of conventional versus online hemodiafiltration from a study in Casablanca, Morocco
Authors: Hazim Asmaa , Adarmouch Latifa , Eloury Aida , Aasfara Jehanne , Asly Mouna , Slassi Ilham
Published: December 2020

Hemodialysis‐related headache (HRH) is a well‐known clinical event. It is considered as one of the most commonly reported neurological symptoms among hemodialysis patients. Its epidemiological, physiological, clinical, and therapeutic data remain scarce and are poorly studied. Our aim was to determine the frequency of HRH in the region of Casablanca, Morocco, to describe its clinical characteristics and to explore the hypothesis that renal replacement techniques, such as conventional versus online hemodiafiltration may have an association on clinical adverse effects like HRH. A descriptive, cross‐sectional, and multicentric study was carried out among 100 chronic hemodialysis patients for at least 6 months. HRH was defined according to criteria published by the International Classification of Headache Disorder third edition beta version (ICHD3β) [1]. Two different HD‐modalities (standard HD and OL‐HDF) have been investigated in order to explore their impact on HRH. Headache was reported by 60% of the patients including 41.6% of hemodialysis‐related headache. HRH had on average a duration of 7.4 hours, pulsatile among 38% of interviewed patients and of moderate intensity in 48% of cases. In total, 51.3% of patients undergoing conventional hemodialysis modality reported HRH compared to 12.5% undergoing online hemodiafiltration technique (OL‐HDF) (P = .008). Hemodialysis‐related headache remains a poorly studied clinical event despite its high prevalence. Its diagnosis, management, and especially its prevention remain a challenge for the neurologist and the nephrologist. Our results suggest that OL‐HDF is a promising therapeutic and preventive tool to reduce the incidence of HRH.