bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing viral diagnostics with model-based optimization
Authors: Metsky Hayden C. , Welch Nicole L. , Pillai Priya P. , Haradhvala Nicholas J. , Rumker Laurie , Mantena Sreekar , Zhang Yibin B. , Yang David K. , Ackerman Cheri M. , Weller Juliane , Blainey Paul C. , Myhrvold Cameron , Mitzenmacher Michael , Sabeti Pardis C.
Published: November 2020

Diagnostics, particularly for rapidly evolving viruses, stand to benefit from a principled, measurement-driven design that harnesses machine learning and vast genomic data—yet the capability for such design has not been previously built. Here, we develop and extensively validate an approach to designing viral diagnostics that applies a learned model within a combinatorial optimization framework. Concentrating on CRISPR-based diagnostics, we screen a library of 19,209 diagnostic–target pairs and train a deep neural network that predicts, from RNA sequence alone, diagnostic signal better than contemporary techniques. Our model then makes it possible to design assays that are maximally sensitive over the spectrum of a virus’s genomic variation. We introduce ADAPT (https://adapt.guide), a system for fully-automated design, and use ADAPT to design optimal diagnostics for the 1,933 vertebrate-infecting viral species within 2 hours for most species and 24 hours for all but 3. We experimentally show ADAPT’s designs are sensitive and specific down to the lineage level, including against viruses that pose challenges involving genomic variation and specificity. ADAPT’s designs exhibit significantly higher fluorescence and permit lower limits of detection, across a virus’s entire variation, than the outputs of standard design techniques. Our model-based optimization strategy has applications broadly to viral nucleic acid diagnostics and other sequence-based technologies, and, paired with clinical validation, could enable a critically-needed, proactive resource of assays for surveilling and responding to pathogens.
MolDiscovery: Learning Mass Spectrometry Fragmentation of Small Molecules
Authors: Cao Liu , Guler Mustafa , Tagirdzhanov Azat , Lee Yiyuan , Gurevich Alexey , Mohimani Hosein
Published: November 2020

Identification of small molecules is a critical task in various areas of life science. Recent advances in mass spectrometry have enabled the collection of tandem mass spectra of small molecules from hundreds of thousands of environments. To identify which molecules are present in a sample, one can search mass spectra collected from the sample against millions of molecular structures in small molecule databases. This is a challenging task as currently it is not clear how small molecules are fragmented in mass spectrometry. The existing approaches use the domain knowledge from chemistry to predict fragmentation of molecules. However, these rule-based methods fail to explain many of the peaks in mass spectra of small molecules. Recently, spectral libraries with tens of thousands of labelled mass spectra of small molecules have emerged, paving the path for learning more accurate fragmentation models for mass spectral database search. We present molDiscovery, a mass spectral database search method that improves both efficiency and accuracy of small molecule identification by (i) utilizing an efficient algorithm to generate mass spectrometry fragmentations, and (ii) learning a probabilistic model to match small molecules with their mass spectra. We show our database search is an order of magnitude more efficient than the state-of-the-art methods, which enables searching against databases with millions of molecules. A search of over 8 million spectra from the Global Natural Product Social molecular networking infrastructure shows that our probabilistic model can correctly identify nearly six times more unique small molecules than previous methods. Moreover, by applying molDiscovery on microbial datasets with both mass spectral and genomics data we successfully discovered the novel biosynthetic gene clusters of three families of small molecules.

Availability

The command-line version of molDiscovery and its online web service through the GNPS infrastructure are available athttps://github.com/mohimanilab/molDiscovery.
Kozak sequence acts as a negative regulator forde novotranscription initiation of newborn coding sequences in the plant genome
Authors: Hata Takayuki , Satoh Soichirou , Takada Naoto , Matsuo Mitsuhiro , Obokata Junichi
Published: November 2020

The manner in which newborn coding sequences and their transcriptional competency emerge during the process of gene evolution remains unclear. Here, we experimentally simulated eukaryotic gene origination processes by mimicking horizontal gene transfer events in the plant genome. We mapped the precise position of the transcription start sites (TSSs) of hundreds of newly introduced promoterless firefly luciferase (LUC) coding sequences in the genome ofArabidopsis thalianacultured cells. The systematic characterization of theLUC-TSSs revealed that 80% of them occurred under the influence of endogenous promoters, while the remainder underwentde novoactivation in the intergenic regions, starting from pyrimidine-purine dinucleotides. Thesede novoTSSs obeyed unexpected rules; they predominantly occurred ~100 bp upstream of theLUCinserts and did not overlap with Kozak-containing putative open reading frames (ORFs). These features were the output of the immediate responses to the sequence insertions, rather than a bias in the screening of theLUCgene function. Regarding the wild-type genic TSSs, they appeared to have evolved to lack any ORFs in their vicinities. Therefore, the repulsion by thede novoTSSs of Kozak-containing ORFs described above might be the first selection gate for the occurrence and evolution of TSSs in the plant genome. Based on these results, we characterized thede novotype of TSS identified in the plant genome and discuss its significance in genome evolution.
Robust and efficient software for reference-free genomic diversity analysis of GBS data on diploid and polyploid species
Authors: Parra-Salazar Andrea , Gomez Jorge , Lozano-Arce Daniela , Reyes-Herrera Paula H. , Duitama Jorge
Published: November 2020

Genotype-by-sequencing (GBS) is a widely used cost-effective technique to obtain large numbers of genetic markers from populations. Although a standard reference-based pipeline can be followed to analyze these reads, a reference genome is still not available for a large number of species. Hence, several research groups require reference-free approaches to generate the genetic variability information that can be obtained from a GBS experiment. Unfortunately, tools to perform de-novo analysis of GBS reads are scarce and some of the existing solutions are difficult to operate under different settings generated by the existing GBS protocols. In this manuscript we describe a novel algorithm to perform reference-free variants detection and genotyping from GBS reads. Non-exact searches on a dynamic hash table of consensus sequences allow to perform efficient read clustering and sorting. This algorithm was integrated in the Next Generation Sequencing Experience Platform (NGSEP) to integrate the state-of- the-art variants detector already implemented in this tool. We performed benchmark experiments with three different real populations of plants and animals with different structures and ploidies, and sequenced with different GBS protocols at different read depths. These experiments show that NGSEP has comparable and in some cases better accuracy and always better computational efficiency compared to existing solutions. We expect that this new development will be useful for several research groups conducting population genetic studies in a wide variety of species.
Predicting and validating protein degradation in proteomes using deep learning
Authors: Ozols Matiss , Eckersley Alexander , Platt Christopher I. , McGuinness Callum S. , Hibbert Sarah A. , Revote Jerico , Li Fuyi , Griffiths Christopher E.M. , Watson Rachel E.B. , Song Jiangning , Bell Mike , Sherratt Michael J.
Published: November 2020

Age, disease, and exposure to environmental factors can induce tissue remodelling and alterations in protein structure and abundance. In the case of human skin, ultraviolet radiation (UVR)-induced photo-ageing has a profound effect on dermal extracellular matrix (ECM) proteins. We have previously shown that ECM proteins rich in UV-chromophore amino acids are differentially susceptible to UVR. However, this UVR-mediated mechanism alone does not explain the loss of UV-chromophore-poor assemblies such as collagen. Here, we aim to develop novel bioinformatics tools to predict the relative susceptibility of human skin proteins to not only UVR and photodynamically produced ROS but also to endogenous proteases. We test the validity of these protease cleavage site predictions against experimental datasets (both previously published and our own, derived by exposure of either purified ECM proteins or a complex cell-derived proteome, to matrix metalloproteinase [MMP]-9). Our deep Bidirectional Recurrent Neural Network (BRNN) models for cleavage site prediction in nine MMPs, four cathepsins, elastase-2, and granzyme-B perform better than existing models when validated against both simple and complex protein mixtures. We have combined our new BRNN protease cleavage prediction models with predictions of relative UVR/ROS susceptibility (based on amino acid composition) into the Manchester Proteome Susceptibility Calculator (MPSC) webapphttp://www.manchesterproteome.manchester.ac.uk/#/MPSC(orhttp://130.88.96.141/#/MPSC). Application of the MPSC to the dermal proteome suggests that fibrillar collagens and elastic fibres will be preferentially degraded by proteases alone and by UVR/ROS and protease in combination, respectively. We also identify novel targets of oxidative damage and protease activity including dermatopontin (DPT), fibulins (EFEMP-1,-2, FBLN-1,-2,-5), defensins (DEFB1, DEFA3, DEFA1B, DEFB4B), proteases and protease inhibitors themselves (CTSA, CTSB, CTSZ, CTSD, TIMPs-1,-2,-3, SPINK6, CST6, PI3, SERPINF1, SERPINA-1,-3,-12). The MPSC webapp has the potential to identify novel protein biomarkers of tissue damage and to aid the characterisation of protease degradomics leading to improved identification of novel therapeutic targets.
Design optimization of metamaterial units using a genetic algorithm based optimization methodology
Authors: Li Yiying , Yang Shiyou
Published: November 2020

Purpose

The purpose of this paper is to develop a pertinent design optimization methodology for symmetric designs of a metamaterial (MM) unit.

Design/methodology/approach

A cell division mechanism is introduced and used to design a new selecting mechanism in the proposed algorithm, a non-dominated sorting cellular genetic algorithm (NSCGA).

Findings

The numerical results on solving standard multi-objective test functions and a prototype MM unit positively demonstrate the advantages of the proposed NSCGA.

Originality/value

A new NSGAII-based optimization algorithm, NSCGA, for multi-objective optimization designs of a MM unit is proposed.
Research on the optimization of the management process on internet of things (Iot) for electronic market
Authors: Zhao Haoyu , Chen Pei-Lin , Khan Shahnawaz , Khalafe Osamah Ibrahim
Published: November 2020

Purpose

Quality is considered one of the essential competitive priorities for managing the Small, Medium Electronics Enterprises (SMEE) market in China; here, the most critical competing priorities and precondition for sector survival and growth are analysed. Instead, small and medium-sized enterprises are significantly disadvantaged and limited to validation capital.

Design/methodology/approach

Quality results are controlled by continuous measurement, irrespective of the product form, as a fundamental issue among firms. Hence, it enables the electronics markets to deal with various aspects of quality programs with effective deployment of IoT-assisted identify management (IIDM) model.

Findings

It enables the electronics markets to deal with various aspects of quality programs with effective deployment of IIDM model available to them without wasting in unimportant and non-productive areas. IIDM makes it essential for SMEEs to analyze total quality management (TQM) towards better understanding the relationship between internal structures and external ones to achieve better quality results.

Originality/value

Analyzes TQM towards better understanding shows the relationship between internal and external structures to achieve better quality results.
How (Not) to Form a Progressive Alliance: Lessons from the History of Left Cooperation
Authors: Ostrowski Marius S.
Published: November 2020

Britain’s political parties can be divided into two blocs: a ‘progressive bloc’ of parties on the left/centre‐left, and a ‘reactionary bloc’ of those on the right/centre‐right. In three of the last four general elections, the progressive bloc won an appreciably larger share of the popular vote than its reactionary rival. Yet its greater internal fragmentation has been repeatedly punished under first past the post, leading to what is now over a decade of Conservative‐led governments. This has prompted growing pressure to form a ‘progressive alliance’ between Labour, Liberal Democrats, Greens, and their Scottish, Welsh and Northern Irish nationalist competitors. This article sheds a historical and international light on these demands, examining the difficulties other similar efforts at progressive cooperation have faced across the world. It considers how progressive alliances have previously sought to overcome geographical, ideological, and social divides between their constituent members, and draws some salutary lessons for British progressives today.
Vascular control by infrarenal aortic cross‐clamping in placenta accreta spectrum disorders: description of technique
Authors: Chou M‐M , Chen M‐J , Su H‐W , Chan C‐W , Kung H‐F , Tseng J‐J , Chen W‐C , Chen Y‐F , Yuan J‐C
Published: November 2020

We describe a novel surgical technique in 31 women with histopathologically confirmed placenta accreta spectrum (PAS) disorders managed by a multidisciplinary team using a prophylactic infrarenal abdominal aortic cross‐clamping technique during caesarean hysterectomy. We conclude that this new surgical procedure is a relatively safe technique to potentially control operative blood loss. Our work may stimulate others to develop protocols assessing this innovative technique to improve the surgical outcome of PAS disorders.
Metal–organic framework for the extraction and detection of pesticides from food commodities
Authors: Xu Yan , Wang Hui , Li Xiangxin , Zeng Xiangquan , Du Zhenjiao , Cao Jiankang , Jiang Weibo
Published: November 2020

Pesticide residues in food matrices, threatening the survival and development of humanity, is one of the critical challenges worldwide. Metal–organic frameworks (MOFs) possess excellent properties, which include excellent adsorption capacity, tailorable shape and size, hierarchical structure, numerous surface‐active sites, high specific surface areas, high chemical stabilities, and ease of modification and functionalization. These promising properties render MOFs as advantageous porous materials for the extraction and detection of pesticides in food samples. This review is based on a brief introduction of MOFs and highlights recent advances in pesticide extraction and detection through MOFs. Furthermore, the challenges and prospects in this field are also described.
Microbial biosurfactant research: time to improve the rigour in the reporting of synthesis, functional characterization and process development
Authors: Twigg Matthew Simon , Baccile Niki , Banat Ibrahim M. , Déziel Eric , Marchant Roger , Roelants Sophie , Van Bogaert Inge N. A.
Published: November 2020

The demand for microbially produced surface‐active compounds for use in industrial processes and products is increasing. As such, there has been a comparable increase in the number of publications relating to the characterization of novel surface‐active compounds: novel producers of already characterized surface‐active compounds and production processes for the generation of these compounds. Leading researchers in the field have identified that many of these studies utilize techniques are not precise and accurate enough, so some published conclusions might not be justified. Such studies lacking robust experimental evidence generated by validated techniques and standard operating procedures are detrimental to the field of microbially produced surface‐active compound research. In this publication, we have critically reviewed a wide range of techniques utilized in the characterization of surface‐active compounds from microbial sources: identification of surface‐active compound producing microorganisms and functional testing of resultant surface‐active compounds. We have also reviewed the experimental evidence required for process development to take these compounds out of the laboratory and into industrial application. We devised this review as a guide to both researchers and the peer‐reviewed process to improve the stringency of future studies and publications within this field of science.
Predicting amphibian intraspecific diversity with machine learning: Challenges and prospects for integrating traits, geography, and genetic data
Authors: Barrow Lisa N. , Masiero da Fonseca Emanuel , Thompson Coleen E. P. , Carstens Bryan C.
Published: November 2020

The growing availability of genetic data sets, in combination with machine learning frameworks, offers great potential to answer long‐standing questions in ecology and evolution. One such question has intrigued population geneticists, biogeographers, and conservation biologists: What factors determine intraspecific genetic diversity? This question is challenging to answer because many factors may influence genetic variation, including life history traits, historical influences, and geography, and the relative importance of these factors varies across taxonomic and geographic scales. Furthermore, interpreting the influence of numerous, potentially correlated variables is difficult with traditional statistical approaches. To address these challenges, we analysed repurposed data using machine learning and investigated predictors of genetic diversity, focusing on Nearctic amphibians as a case study. We aggregated species traits, range characteristics, and >42,000 genetic sequences for 299 species using open‐access scripts and various databases. After identifying important predictors of nucleotide diversity with random forest regression, we conducted follow‐up analyses to examine the roles of phylogenetic history, geography, and demographic processes on intraspecific diversity. Although life history traits were not important predictors for this data set, we found significant phylogenetic signal in genetic diversity within amphibians. We also found that salamander species at northern latitudes contained low genetic diversity. Data repurposing and machine learning provide valuable tools for detecting patterns with relevance for conservation, but concerted efforts are needed to compile meaningful data sets with greater utility for understanding global biodiversity.
Quantifying phagocytic lymphocytes in ectothermic vertebrates: A simplified technique for assessing immune function
Authors: Slama Summer L. , Painter Mariah N. , Sheedy Maxwell D. , Sandmeier Franziska C.
Published: November 2020

Many measures of immune function used in ecoimmunological studies were optimized for endotherms and may not adequately characterize immunocompetence in ectothermic species. Lymphocytes are interpreted as functioning in adaptive immunity despite evidence that large proportions of these cells have innate immune functions, including phagocytosis, in ectotherms.

We modified previously published protocols to remove many barriers that inhibited the wide application of assays to quantify phagocytic activity in lymphocytes. These barriers included the use of species‐specific reagents, high cost and incompatibility with field work. We statistically compared published methods to our simplified technique using blood samples collected from tortoises.

We show the efficacy of the new technique and offer an outline for optimizing these methods for different species and to address a wide variety of ecoimmunological questions.

A full understanding of immune function in ectothermic vertebrates is needed to comprehend complex epidemiological patterns. As our assay disentangles the relationship between effector cells (lymphocytes) and their function (phagocytosis), these methods provide a foundation for more thorough analyses of ecoimmunological patterns.
Derivation With Internal Validation of a Multivariable Predictive Model to Predict COVID‐19 Test Results in Emergency Department Patients
Authors: McDonald Samuel A. , Medford Richard J. , Basit Mujeeb A. , Diercks Deborah B. , Courtney D. Mark
Published: November 2020

Objectives

The COVID‐19 pandemic has placed acute care providers in demanding situations in predicting disease given the clinical variability, desire to cohort patients, and high variance in testing availability. An approach to stratifying patients by likelihood of disease based on rapidly available emergency department (ED) clinical data would offer significant operational and clinical value. The purpose of this study was to develop and internally validate a predictive model to aid in the discrimination of patients undergoing investigation for COVID‐19.

Methods

All patients greater than 18 years presenting to a single academic ED who were tested for COVID‐19 during this index ED evaluation were included. Outcome was defined as the result of COVID‐19 polymerase chain reaction (PCR) testing during the index visit or any positive result within the following 7 days. Variables included chest radiograph interpretation, disease‐specific screening questions, and laboratory data. Three models were developed with a split‐sample approach to predict outcome of the PCR test utilizing logistic regression, random forest, and gradient‐boosted decision tree methods. Model discrimination was evaluated comparing area under the receiver operator curve (AUC) and point statistics at a predefined threshold.

Results

A total of 1,026 patients were included in the study collected between March and April 2020. Overall, there was disease prevalence of 9.6% in the population under study during this time frame. The logistic regression model was found to have an AUC of 0.89 (95% confidence interval [CI] = 0.84 to 0.94) when including four features: exposure history, temperature, white blood cell count (WBC), and chest radiograph result. Random forest method resulted in AUC of 0.86 (95% CI = 0.79 to 0.92) and gradient boosting had an AUC of 0.85 (95% CI = 0.79 to 0.91). With a consistently held negative predictive value, the logistic regression model had a positive predictive value of 0.29 (0.2–0.39) compared to 0.2 (0.14–0.28) for random forest and 0.22 (0.15–0.3) for the gradient‐boosted method.

Conclusion

The derived predictive models offer good discriminating capacity for COVID‐19 disease and provide interpretable and usable methods for those providers caring for these patients at the important crossroads of the community and the health system. We found utilization of the logistic regression model utilizing exposure history, temperature, WBC, and chest X‐ray result had the greatest discriminatory capacity with the most interpretable model. Integrating a predictive model‐based approach to COVID‐19 testing decisions and patient care pathways and locations could add efficiency and accuracy to decrease uncertainty.
Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A)
Authors: Kim You Ran , Yi MyeongJin , Cho Sun‐Ah , Kim Woo‐Young , Min JungKi , Shin Jae‐Gook , Lee Su‐Jun
Published: November 2020

Phosphodiesterase 3A (PDE3A) is an enzyme that plays an important role in the regulation of cyclic adenosine monophosphate (cAMP)–mediated intracellular signaling in cardiac myocytes and platelets. PDE3A hydrolyzes cAMP, which results in a decrease in intracellular cAMP levels and leads to platelet activation. Whole‐exome sequencing of 50 DNA samples from a healthy Korean population revealed a total of 13 single nucleotide polymorphisms including five missense variants, D12N, Y497C, H504Q, C707R, and A980V. Recombinant proteins for the five variants of PDE3A (and wild‐type protein) were expressed in a FreeStyle 293 expression system with site‐directed mutagenesis. The expression of the recombinant PDE3A proteins was confirmed with Western blotting. Catalytic activity of the PDE3A missense variants and wild‐type enzyme was measured with a PDE‐based assay. Effects of the missense variants on the inhibition of PDE3A activity by cilostazol were also investigated. All variant proteins showed reduced activity (33–53%; p < .0001) compared to the wild‐type protein. In addition, PDE3A activity was inhibited by cilostazol in a dose‐dependent manner and was further suppressed in the missense variants. Specifically, the PDE3A Y497C showed significantly reduced activity, consistent with the predictions of in silico analyses. The present study provides evidence that individuals carrying the PDE3A Y497C variant may have lower enzyme activity for cAMP hydrolysis, which could cause interindividual variation in cAMP‐mediated physiological functions.
Increased maternal body mass index is associated with prolonged anaesthetic and surgical times for caesarean delivery but is partially offset by clinician seniority and established epidural analgesia
Authors: Lawrence Sue , Malacova Eva , Reutens David , Sturgess David J.
Published: November 2020

Background

Obesity is associated with higher surgical and anaesthetic morbidity and difficulties.

Aims

We aimed to investigate associations between maternal body mass index (BMI) and the in‐theatre time taken to produce an anaesthetised state or to perform surgery for caesarean delivery.

Materials and Methods

Using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, we identified all women who underwent caesarean section at a single institution (2009–2015). The prospectively collected data arising from antenatal and peripartum care were analysed. Generalised linear regression was used to examine associations between maternal BMI and the time taken to anaesthetise the mother and the duration of surgery.

Results

Of a total of 24 761 caesarean deliveries, 5607 (22.7%) women were obese at antenatal registration. In‐theatre anaesthetic preparation (18 vs 32 min, P < 0.001) and surgical duration (38 vs 52 min, P < 0.001) were longer in women with BMI ≥50 kg/m2 (BMI‐50) than those with normal BMI (BMI‐N). This difference remained significant after controlling for antenatal, intra‐operative and immediate postoperative variables. Modifiable variables were identified that may mitigate the effects of severe obesity. Senior obstetric and anaesthetic care were both independently associated with a significant reduction in mean in‐theatre anaesthetic preparation time and surgical duration, by 11 and three minutes respectively (P < 0.001), while epidural top‐up significantly lessened mean anaesthetic in‐theatre preparation duration by seven minutes (P < 0.001).

Conclusions

Obese women had greater anaesthesia and surgery time, but the effect may potentially be mitigated by provision of care by experienced staff and prior establishment of epidural analgesia.
Assessment of infections rate due to community‐acquired Methicillin‐resistant Staphylococcus aureus and evaluation of risk factors in the paediatric population
Authors: Galper Ella , Bdolah‐Abram Tali , Megged Orli
Published: November 2020

Aim

We aimed at assessing the frequency of Community‐acquired Methicillin‐resistant Staphylococcus aureus (CA‐MRSA) infections, identifying its risk factors and evaluating resistance patterns of Staphylococcus aureus to various antibiotics in order to recommend the optimal empirical treatment for suspected Staphylococcus aureus infections.

Methods

We reviewed the medical records of children who were treated at Shaare Zedek medical centre, located in Jerusalem, Israel, over the years 2008–2019 and had a positive culture for Staphylococcus aureus. Patients with CA‐MRSA infections were compared with Methicillin‐susceptible Staphylococcus aureus (CA‐MSSA) infections.

Results

In this study, 620 paediatric patients were included. The number of children in the CA‐MRSA study group was 124, while the MSSA control group consisted of 496 children. Risk factors for CA‐MRSA infections included young age (1–5 years), female sex, Arab ethnicity and residence in East Jerusalem. The incidence of CA‐MRSA increased over the past decade, with an average of 11.2%. An increase in MSSA resistance to clindamycin was noted while Trimethoprim‐Sulphamethoxazole resistance remained low.

Conclusion

The incidence of CA‐MRSA in Jerusalem was rising, along with changes in resistance patterns of both MSSA and MRSA to various antibiotic agents. In order to optimise empirical treatment for suspected staphylococcal infection, continued monitoring of CA‐MRSA prevalence and resistance rates is essential.
Data Collection via Online Platforms: Challenges and Recommendations for Future Research
Authors: Newman Alexander , Bavik Yuen Lam , Mount Matthew , Shao Bo
Published: November 2020

Online platforms such as Amazon's Mechanical Turk (MTurk) are increasingly used by researchers to collect survey and experimental data. Yet, such platforms often represent a tumultuous terrain for both researchers and reviewers. Researchers have to navigate the complexities of obtaining representative samples from online participant cohorts, ensuring data quality, ethically incentivizing participant engagement, and maintaining transparency. Reviewers, on the other hand, have to navigate the complexities of evaluating the efficacy of such data collection and execution efforts in answering important research questions. In order to provide clarity to these issues, this article provides researchers and reviewers with a series of recommendations for effectively executing and evaluating data collection via online platforms, respectively.
Obtaining optimal cutoff values for tree classifiers using multiple biomarkers
Authors: Zhu Yuxin , Wang Mei‐Cheng
Published: November 2020

In biomedical practices, multiple biomarkers are often combined using a prespecified classification rule with tree structure for diagnostic decisions. The classification structure and cutoff point at each node of a tree are usually chosen on an ad hoc basis, depending on decision makers' experience. There is a lack of analytical approaches that lead to optimal prediction performance, and that guide the choice of optimal cutoff points in a pre‐specified classification tree. In this paper, we propose to search for and estimate the optimal decision rule through an approach of rank correlation maximization. The proposed method is flexible, theoretically sound, and computationally feasible when many biomarkers are available for classification or prediction. Using the proposed approach, for a prespecified tree‐structured classification rule, we can guide the choice of optimal cutoff points at tree nodes and estimate optimal prediction performance from multiple biomarkers combined.
Cell‐derived microparticles and sickle cell disease chronic vasculopathy in sub‐Saharan Africa: A multinational study
Authors: Dembélé Abdoul K. , Lapoumeroulie Claudine , Diaw Mor , Tessougue Oumarou , Offredo Lucile , Diallo Dapa A. , Diop Saliou , Elion Jacques , Colin‐Aronovicz Yves , Tharaux Pierre‐Louis , Jouven Xavier , Romana Marc , Ranque Brigitte , Le Van Kim Caroline
Published: November 2020

Although most individuals with sickle cell disease (SCD) live in sub‐Saharan Africa, the natural history of the disease on this continent remains largely unknown. Intravascular haemolysis results in activation of circulating blood cells and release of microparticles (MPs) that exert pro‐inflammatory effects and contribute to vascular damage. We designed a case‐control study nested in the CADRE cohort (Coeur‐Artère‐DRÉpanocytose, clinical trials.gov identifier NCTO3114137) and based on extreme phenotypes, to analyse blood cell‐derived MPs in 232 adult SS patients at steady state in Bamako and Dakar. Thirty‐six healthy adult controls matched by age and sex were recruited in Bamako. The MPs concentrations were higher in SS patients compared to AA controls with a predominance of erythrocyte‐ and reticulocyte‐derived MPs. These erythroid‐derived MPs were significantly lower in patients with retinopathy (P = 0·022). Reticulocyte‐derived MPs were significantly negatively and positively associated with a history of priapism (P = 0·020) and leg ulcers (P = 0·041) respectively. We describe for the first time the comparative patterns of plasma MPs in healthy subjects and

patients with SCD living in sub‐Saharan Africa and exhibiting various complications. Because our present results show no clear pattern of correlation between erythroid MPs and the classical hyper‐haemolytic complications, we hypothesise a weak relevance of the hyper‐haemolysis versus hyper‐viscous paradigm in Africa.
Iodine status in UK–An accidental public health triumph gone sour
Authors: Woodside Jayne V. , Mullan Karen R.
Published: November 2020

The improvement in iodine status among the UK population from the 1930s onwards has been described as an ‘accidental public health triumph’ despite the lack of any iodine fortification program. However, iodine deficiency in the UK has re‐emerged in vulnerable groups and is likely due to a combination of changing farming practices, dietary preferences and public health priorities. The UK is now among only a minority of European countries with no legislative framework for iodine fortification. The experience of folic acid fortification and the 28‐year delay in its implementation lays bare the political difficulties of introducing any fortification program in the UK. If iodine fortification is not an imminent possibility, then it is important to explore other options: how to change farming practice especially on organic farms; encourage dairy intake; protect and expand our public health programs of milk provision for vulnerable groups and embark on education programs for women of childbearing potential and healthcare professionals. This review explores how the UK may have arrived at this juncture and how the iodine status of the nation may be improved at this time of major political and public health upheaval.
Tooth agenesis: What do we know and is there a connection to cancer?
Authors: Bonczek Ondrej , Krejci Premysl , Izakovicova‐Holla Lydie , Cernochova Pavlina , Kiss Igor , Vojtesek Borivoj
Published: November 2020

Like all developmental processes, odontogenesis is highly complex and dynamically regulated, with hundreds of genes co‐expressed in reciprocal networks. Tooth agenesis (missing one or more/all teeth) is a common human craniofacial anomaly and may be caused by genetic variations and/or environmental factors. Variants in PAX9, MSX1, AXIN2, EDA, EDAR, and WNT10A genes are associated with tooth agenesis. Currently, variants in ATF1, DUSP10, CASC8, IRF6, KDF1, GREM2, LTBP3, and components and regulators of WNT signaling WNT10B, LRP6, DKK, and KREMEN1 are at the forefront of interest. Due to the interconnectedness of the signaling pathways of carcinogenesis and odontogenesis, tooth agenesis could be a suitable marker for early detection of cancer predisposition. Variants in genes associated with tooth agenesis could serve as prognostic or therapeutic targets in cancer. This review aims to summarize existing knowledge of development and clinical genetics of teeth. Concurrently, the review proposes possible approaches for future research in this area, with particular attention to roles in monitoring, early diagnosis and therapy of tumors associated with defective tooth development.
International clinical practice recommendations on the definition, diagnosis, assessment, intervention, and psychosocial aspects of developmental coordination disorder – Chinese (Mandarin) translation
Authors: Hua Jing , Du Wenchong , Dai Xiaotian , Wu Meiqin , Cai Xianying , Shen Min , Zhu Liping
Published: November 2020

目的

本国际临床指南由欧洲残疾儿童学会（the European Academy of Childhood Disability，EACD）牵头制定，旨在解决发育性协调障碍（developmental coordination disorder，DCD）的定义、诊断、评估、干预以及与社会心理方面的临床应用关键问题。

方法

本指南针对五个领域的关键问题，通过文献综述和专家团队的正式讨论达成共识。为保证指南的循证基础，以“机制”、“评估”和“干预”为检索词, 对2012年更新以来提出的最新建议以及新增的“社会心理问题”和“青少年/成人”为检索词进行检索。根据牛津大学循证医学中心证据等级 (证据水平 [level of evidence, LOE]1–4) 将结果进行分类，最终转化为指南建议。并由国际、多学科专家小组举行了两次会议，5个回合的Delphi 专家问卷调查，制定了高质量临床应用实践 (good clinical practice，GCP) 。

结果

本指南共制定35条建议。其中8条以文献综述为依据 (3 条涉及“评估”，5条涉及“干预”)； 22 条在 2012 年指南的基础上进行了更新；其他为涉及诊断、评估 (3条GCP) 及社会心理问题 (2 条 GCP) 的新建议。此外，其中有1条(LOE)新建议提出视频游戏可作为以活动和参与为导向的传统干预措施的辅助手段，并针对青少年和成人DCD提出了 2 条新建议 (1 条 GCP，1 条 LOE)。

结论

本指南是基于当前的研究证据和专家共识对DCD进行全面概述。它反映了不同学科临床和科研人员的最新科技水平。本国际指南可作为各国制定指南的基础。
Spatial variation in invasive silver carp population ecology throughout the upper Mississippi River basin*
Authors: Sullivan Christopher J. , Weber Michael J. , Pierce Clay L. , Wahl David H. , Phelps Quinton E. , Colombo Robert E.
Published: November 2020

Understanding spatial variation in non‐native fish species population ecology is imperative, where environmental, biotic and invasion‐related mechanisms contribute to spatial heterogeneity. Established populations of invasive silver carp Hypophthalmichthys molitrix are currently found throughout a large portion of the upper Mississippi River (UMR) basin. Despite their recent invasion and broad environmental tolerances, silver carp population ecology and linkages to environmental conditions in the UMR remain understudied. There were two objectives for this investigation: (a) to estimate correlations among population characteristics and the influence of latitude and the time since first detection, and (b) to model the influence of river discharge and temperature on growth early in life to age 3. We estimated spatial variability in silver carp population characteristics and dynamics from nine sites across the UMR and assessed if biotic, abiotic or invasion‐related (time since first detection) variables influence spatial patterns. Silver carp body weight, size structure, annual mortality, and growth parameters varied among locations. Silver carp recruitment was less stable for populations with higher relative abundance estimates and where carp were first detected ≥20 years ago whereas maximum carp age decreased with increasing latitude. Although model selection indicated silver carp length at age 3 was associated with mean daily discharge (m3/s) coefficient of variation, mean May‐June temperatures, and ordinal date of maximum discharge, parameter coefficients and effect sizes were small and not biologically meaningful. Our results suggest that silver carp populations are governed by intraspecific mechanisms, but time‐dependent changes in populations may partially underpin heterogeneity across populations. Our study helped further disentangle silver carp population ecology in the UMR by understanding carp ecology as a function of their invasion.
Inborn differences in emotional behavior coincide with alterations in hypothalamic paraventricular motor projections
Authors: Shupe Elizabeth A. , Glover Matthew E. , Unroe Keaton A. , Kerman Ilan A. , Clinton Sarah M.
Published: November 2020

Integrated behavioral responses to emotionally salient stimuli require the concomitant activation of descending neural circuits that integrate physiological, affective, and motor responses to stress. Our previous work interrogated descending circuits in the brainstem and spinal cord that project to motor and sympathetic targets. The hypothalamic paraventricular nucleus (PVN), a key node of this circuitry, integrates multiple motor and sympathetic responses activated by stress. The present study sought to determine whether descending projections from the PVN to targets in muscle and adrenal gland are differentially organized in rats with inborn differences in emotionality and stress responsivity. We utilized retrograde transsynaptic tract‐tracing with unique pseudorabies virus (PRV) recombinants that were injected into sympathectomized gastrocnemius muscle and adrenal gland in two rat models featuring inborn differences in emotional behavior. Our tract‐tracing results revealed a significant decrease in the number of PVN neurons with poly‐synaptic projections to the gastrocnemius in male Wistar Kyoto [WKY] rats (versus Sprague Dawley rats) and selectively bred Low Novelty Responder [bLR] rats (versus selectively bred High Novelty Responder [bHR] rats). These neuroanatomical differences mirrored behavioral observations showing that both WKY and bLR rats display marked inhibition of emotional motor responses in a variety of settings relative to their respective controls. Our findings suggest that, in male rodents, PVN poly‐synaptic projections to skeletal muscle may regulate emotional motor and coping responses to stress. More broadly, perturbations in PVN motor circuitry may play a role in mediating psychomotor disturbances observed in depression or anxiety‐related disorders.
Characterizing patterns of genomic variation in the threatened Utah prairie dog: Implications for conservation and management
Authors: Giglio Rachael M. , Rocke Tonie E. , Osorio Jorge E. , Latch Emily K.
Published: November 2020

Utah prairie dogs (Cynomys parvidens) are federally threatened due to eradication campaigns, habitat destruction, and outbreaks of plague. Today, Utah prairie dogs exist in small, isolated populations, making them less demographically stable and more susceptible to erosion of genetic variation by genetic drift. We characterized patterns of genetic structure at neutral and putatively adaptive loci in order to evaluate the relative effects of genetic drift and local adaptation on population divergence. We sampled individuals across the Utah prairie dog species range and generated 2955 single nucleotide polymorphisms using double digest restriction site‐associated DNA sequencing. Genetic diversity was lower in low‐elevation sites compared to high‐elevation sites. Population divergence was high among sites and followed an isolation‐by‐distance model. Our results indicate that genetic drift plays a substantial role in the population divergence of the Utah prairie dog, and colonies would likely benefit from translocation of individuals between recovery units, which are characterized by distinct elevations, despite the detection of environmental associations with outlier loci. By understanding the processes that shape genetic structure, better informed decisions can be made with respect to the management of threatened species to ensure that adaptation is not stymied.
Leaching of dissolved organic carbon from mineral soils plays a significant role in the terrestrial carbon balance
Authors: Nakhavali Mahdi , Lauerwald Ronny , Regnier Pierre , Guenet Bertrand , Chadburn Sarah , Friedlingstein Pierre
Published: November 2020

The leaching of dissolved organic carbon (DOC) from soils to the river network is an overlooked component of the terrestrial soil C budget. Measurements of DOC concentrations in soil, runoff and drainage are scarce and their spatial distribution highly skewed towards industrialized countries. The contribution of terrestrial DOC leaching to the global‐scale C balance of terrestrial ecosystems thus remains poorly constrained. Here, using a process based, integrative, modelling approach to upscale from existing observations, we estimate a global terrestrial DOC leaching flux of 0.28 ± 0.07 Gt C year−1 which is conservative, as it only includes the contribution of mineral soils. Our results suggest that globally about 15% of the terrestrial Net Ecosystem Productivity (NEP, calculated as the difference between Net Primary Production and soil respiration) is exported to aquatic systems as leached DOC. In the tropical rainforest, the leached fraction of terrestrial NEP even reaches 22%. Furthermore, we simulated spatial‐temporal trends in DOC leaching from soil to the river networks from 1860 to 2010. We estimated a global increase in terrestrial DOC inputs to river network of 35 Tg C year−1 (14%) from 1860 to 2010. Despite their low global contribution to the DOC leaching flux, boreal regions have the highest relative increase (28%) while tropics have the lowest relative increase (9%) over the historical period (1860s compared to 2000s). The results from our observationally constrained model approach demonstrate that DOC leaching is a significant flux in the terrestrial C budget at regional and global scales.
Climate, urbanization, and species traits interactively drive flowering duration
Authors: Li Daijiang , Barve Narayani , Brenskelle Laura , Earl Kamala , Barve Vijay , Belitz Michael W. , Doby Joshua , Hantak Maggie M. , Oswald Jessica A. , Stucky Brian J. , Walters Mitch , Guralnick Robert P.
Published: November 2020

A wave of green leaves and multi‐colored flowers advances from low to high latitudes each spring. However, little is known about how flowering offset (i.e., ending of flowering) and duration of populations of the same species vary along environmental gradients. Understanding these patterns is critical for predicting the effects of future climate and land‐use change on plants, pollinators, and herbivores. Here, we investigated potential climatic and landscape drivers of flowering onset, offset, and duration of 52 plant species with varying key traits. We generated phenology estimates using >270,000 community‐science photographs and a novel presence‐only phenometric estimation method. We found longer flowering durations in warmer areas, which is more obvious for summer‐blooming species compared to spring‐bloomers driven by their strongly differing offset dynamics. We also found that higher human population density and higher annual precipitation are associated with delayed flowering offset and extended flowering duration. Finally, offset of woody perennials was more sensitive than herbaceous species to both climate and urbanization drivers. Empirical forecast models suggested that flowering durations will be longer in 2030 and 2050 under representative concentration pathway (RCP) 8.5, especially for summer‐blooming species. Our study provides critical insight into drivers of key flowering phenophases and confirms that Hopkins’ Bioclimatic Law also applies to flowering durations for summer‐blooming species and herbaceous spring‐blooming species.