bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Anatomical Features of Alveolar Cleft in Unilateral Cleft Lip and Palate Patients of Different Ages
Authors: Wei Shuaishuai , Wang Yuli , Ma Xiaojie , Pan Yongchu , Zhang Ping , Jiang Hongbing , Du Yifei , Wan Linzhong
Published: August 2020

Objectives:

This study aimed to compare the anatomical features of alveolar cleft in patients with complete unilateral cleft lip and palate (UCLP) of different ages.

Methods:

Sixty UCLP patients were divided into 3 groups as follows: group 1 (7–12 years old), group 2 (13–18 years old) and group 3 (more than 18 years old). The radiographic images were analyzed based on cone beam computed tomography (CBCT) images.

Results:

The mean age in 3 groups was 10.45 ± 1.15, 15.05 ± 1.90, and 22.55 ± 3.00 years (P < 0.0001). The lip-palatal width in Group 2 and 3 was 15.14 ± 3.67 mm3 and 15.50 ± 3.92 mm3, which was significantly larger than 12.97 ± 1.82 mm in Group 1 (P = 0.037). The volume of alveolar defect was 1.09 ± 0.23 cm3, 1.28 ± 0.38 cm3 and 1.40 ± 0.58 cm3 in 3 groups, and the difference between any 2 of them was significant (P = 0.0004). The prevalence of ipsilateral but contralateral maxillary sinusitis was significant among 3 groups (P = 0.0015) while the other nasal deformities including nasal septum deviation and inferior turbinate hypertrophy was not found significant.

Conclusions:

Alveolar cleft volume increased with age, which is properly due to enlarged width of lip-palatal defect. The significant higher frequencies of ipsilateral maxillary sinusitis in patients under 18 could increase the risk of bone infection.
Endoscopic Endonasal Orbital Floor Fracture Repair With Mucosal Preservation to Reinforce the Fractured Bone
Authors: Omura Kazuhiro , Nomura Kazuhiro , Okushi Tetsushi , Tanaka Yasuhiro , Otori Nobuyoshi
Published: August 2020

Treatment of orbital floor fracture is often needed to cure diplopia and enophthalmos. However, the available surgical methods have many limitations. An endoscopic endonasal reduction is a familiar approach for otolaryngologists; however, reconstruction of the orbital floor may pose certain problems. Here, the authors developed the endoscopic endonasal orbital floor fracture repair with mucosal preservation procedure (mucosal preservation procedure). This study aims to evaluate outcomes after the mucosal preservation procedure. The authors analyzed 18 patients who had their orbital floor repaired using the mucosal preservation procedure. Pre- and post-operative ocular motility range was measured with a Hess screen test, and the percentage of Hess area ratio (HAR%) was used for all statistical comparisons. The distance between the fractured bone and orbital floor (DBFO) on computed tomography was measured before and four months after surgery. Overall, diplopia, and pain improved after surgery in all patients. Diplopia and pain completely disappeared in 17 patients, while only mild diplopia remained in one. HAR% increased significantly, whereas DBFO reduced significantly after the operation. In conclusion, the outcome of the mucosal preservation procedure was favorable without any major complications. Further studies with larger numbers of patients are needed to verify our technique.
Situating Artificial Intelligence in Surgery
Authors: Korndorffer James R. , Hawn Mary T. , Spain David A. , Knowlton Lisa M. , Azagury Dan E. , Nassar Aussama K. , Lau James N. , Arnow Katherine D. , Trickey Amber W. , Pugh Carla M.
Published: August 2020

Objectives:

Artificial intelligence (AI) has numerous applications in surgical quality assurance. We assessed AI accuracy in evaluating the critical view of safety (CVS) and intraoperative events during laparoscopic cholecystectomy. We hypothesized that AI accuracy and intraoperative events are associated with disease severity.

Methods:

One thousand fifty-one laparoscopic cholecystectomy videos were annotated by AI for disease severity (Parkland Scale), CVS achievement (Strasberg Criteria), and intraoperative events. Surgeons performed focused video review on procedures with ≥1 intraoperative events (n = 335). AI versus surgeon annotation of CVS components and intraoperative events were compared. For all cases (n = 1051), intraoperative-event association with CVS achievement and severity was examined using ordinal logistic regression.

Results:

Using AI annotation, surgeons reviewed 50 videos/hr. CVS was achieved in ≤10% of cases. Hepatocystic triangle and cystic plate visualization was achieved more often in low-severity cases (P < 0.03). AI-surgeon agreement for all CVS components exceeded 75%, with higher agreement in high-severity cases (P < 0.03). Surgeons agreed with 99% of AI-annotated intraoperative events. AI-annotated intraoperative events were associated with both disease severity and number of CVS components not achieved. Intraoperative events occurred more frequently in high-severity versus low-severity cases (0.98 vs 0.40 events/case, P < 0.001).

Conclusions:

AI annotation allows for efficient video review and is a promising quality assurance tool. Disease severity may limit its use and surgeon oversight is still required, especially in complex cases. Continued refinement may improve AI applicability and allow for automated assessment.
Hereditary motor neuropathies
Authors: Dohrn Maike F. , Saporta Mario
Published: August 2020

Purpose of review

Hereditary motor neuropathies (HMN) comprise a broad genotypic and phenotypic spectrum of rare, progressively disabling diseases manifesting with length-dependent muscle weakness and atrophy. To date, more than half of the cases cannot be genetically explained. To provide symptomatic and disease-modifying treatments in the future, a better understanding of disease mechanisms is required.

Recent findings

By whole exome and genome sequencing, the discovery of several novel genes (SCO2, TDRKH, SPTAN1, CADM3, and SORD) involved in the pathogenesis of HMN has now relevantly changed the pathophysiological knowledge. This recent success in causative understanding has mainly been driven by the development of functional models including cell culture, animal, and patient-derived induced pluripotent stem cell platforms. These models have an important impact on therapeutic advances including broader approaches to prevent or reverse axonal degeneration and individualized gene silencing attempts using sequence-specific RNA degradation mechanisms.

In rare diseases such as HMN, the recent development of genetic sequencing and data interpretation methods has enabled a broader diagnostic approach, whereas treatment strategies are becoming more individualized. Significant milestones have been reached in the discovery of new genes, the establishment of functional disease models, and the preclinical development of mechanistic-based therapies.
Wilbrand's Knee: To Be or Not to Be a Knee?
Authors: Horton Jonathan C.
Published: August 2020

Wilbrand's knee of the optic chiasm refers to crossing fibers from one optic nerve that stray for a short distance into the opposite optic nerve before joining the optic tract. This loop of aberrant axons, although small, has generated much controversy. In a previous study, labeling of the optic pathway in normal monkeys with a radioactive tracer revealed no Wilbrand's knee. Monocular enucleation induced a typical knee to form. These findings suggested that Wilbrand's knee is absent normally, but appears after atrophy of one optic nerve. This conclusion has been challenged by images showing Wilbrand's knee in the normal human chiasm using anisotropic light scattering. It has also been resisted by some clinicians who believe that Wilbrand's knee is necessary to explain the anterior chiasmal syndrome. Early in his distinguished career, William F. Hoyt examined the fiber organization of the monkey optic nerve and chiasm. He found no evidence for Wilbrand's knee and rejected its importance for the topical diagnosis of chiasmal lesions. His conclusion is supported by new data showing that anisotropic light scattering is not a reliable method for tracing axons. Hence, that method has given a misleading impression that Wilbrand's knee exists in normal subjects. Although Wilbrand's knee has fascinated neuro-ophthalmologists for more than a century, it is an inconsequential structure that develops only after a longstanding monocular optic neuropathy.
Uses of pathogen detection data to estimate vaccine direct effects in case–control studies
Authors: Lewnard Joseph A.
Published: August 2020

The fact that many pathogens can be carried or shed without causing symptoms complicates the interpretation of microbiological data when diagnosing certain infectious disease syndromes. Diagnostic criteria that attribute symptoms to a pathogen which is detectable, whether it is or is not the aetiological agent of disease, may lead to outcome misclassification in epidemiological studies. Case–control studies are commonly undertaken to estimate vaccine effectiveness (VE) and present an opportunity to compare pathogen detection among individuals with and without clinically relevant symptoms. Considering this study context, we present a mathematical framework yielding simple estimators for the direct effects of vaccination on various aspects of host susceptibility. These include protection against acquisition of the pathogen of interest and protection against progression of this pathogen to disease following acquisition. We assess the impact of test sensitivity on these estimators and extend our framework to identify a ‘vaccine probe’ estimator for pathogen-specific aetiological fractions. We also derive biases affecting VE estimates under the test-negative design, a special case enrolling only symptomatic persons. Our results provide strategies for estimating pathogen-specific VE in the absence of a diagnostic gold standard. These approaches can inform the design and analysis of studies addressing numerous pathogens and vaccines.
Assessment of surface roughness and blood rheology on local coronary haemodynamics: a multi-scale computational fluid dynamics study
Authors: Owen David G. , Schenkel Torsten , Shepherd Duncan E. T. , Espino Daniel M.
Published: August 2020

The surface roughness of the coronary artery is associated with the onset of atherosclerosis. The study applies, for the first time, the micro-scale variation of the artery surface to a 3D coronary model, investigating the impact on haemodynamic parameters which are indicators for atherosclerosis. The surface roughness of porcine coronary arteries have been detailed based on optical microscopy and implemented into a cylindrical section of coronary artery. Several approaches to rheology are compared to determine the benefits/limitations of both single and multiphase models for multi-scale geometry. Haemodynamic parameters averaged over the rough/smooth sections are similar; however, the rough surface experiences a much wider range, with maximum wall shear stress greater than 6 Pa compared to the approximately 3 Pa on the smooth segment. This suggests the smooth-walled assumption may neglect important near-wall haemodynamics. While rheological models lack sufficient definition to truly encompass the micro-scale effects occurring over the rough surface, single-phase models (Newtonian and non-Newtonian) provide numerically stable and comparable results to other coronary simulations. Multiphase models allow for phase interactions between plasma and red blood cells which is more suited to such multi-scale models. These models require additional physical laws to govern advection/aggregation of particulates in the near-wall region.
Unobtrusive tracking of interpersonal orienting and distance predicts the subjective quality of social interactions
Authors: Lahnakoski Juha M. , Forbes Paul A.G. , McCall Cade , Schilbach Leonhard
Published: August 2020

Interpersonal coordination of behaviour is essential for smooth social interactions. Measures of interpersonal behaviour, however, often rely on subjective evaluations, invasive measurement techniques or gross measures of motion. Here, we constructed an unobtrusive motion tracking system that enables detailed analysis of behaviour at the individual and interpersonal levels, which we validated using wearable sensors. We evaluate dyadic measures of joint orienting and distancing, synchrony and gaze behaviours to summarize data collected during natural conversation and joint action tasks. Our results demonstrate that patterns of proxemic behaviours, rather than more widely used measures of interpersonal synchrony, best predicted the subjective quality of the interactions. Increased distance between participants predicted lower enjoyment, while increased joint orienting towards each other during cooperation correlated with increased effort reported by the participants. Importantly, the interpersonal distance was most informative of the quality of interaction when task demands and experimental control were minimal. These results suggest that interpersonal measures of behaviour gathered during minimally constrained social interactions are particularly sensitive for the subjective quality of social interactions and may be useful for interaction-based phenotyping for further studies.
Investigation of damping effects on low-frequency steady-state acoustical behaviour of coupled spaces
Authors: Meissner Mirosław , Wiśniewski Krzysztof
Published: August 2020

In the low-frequency range, the acoustical behaviour of enclosed spaces is strongly influenced by excited acoustic modes resulting in a spatial irregularity of a steady-state sound field. In the paper, this problem has been examined theoretically and numerically for a system of coupled spaces with complex-valued conditions on boundary surfaces. Using a modal expansion method, an analytic formula for Green’s function was derived allowing to predict the interior sound field for a pure-tone excitation. To quantify the spatial irregularity of steady-state sound field, the parameter referred to as the mean spatial deviation was introduced. A numerical simulation was carried out for the system consisting of two coupled rectangular subspaces. Eigenfunctions and eigenfrequencies for this system were determined using the high-accuracy eigenvalue solver. As was evidenced by computational data, for small sound damping on absorptive walls the mean spatial deviation peaks at frequencies corresponding to eigenfrequencies of strongly localized modes. However, if the sound damping is much higher, the main cause of spatial irregularity of the interior sound field is the appearance of sharp valleys in a spatial distribution of a sound pressure level.
The diversity of maternal-age effects upon pre-adult survival across animal species
Authors: Ivimey-Cook Edward , Moorad Jacob
Published: August 2020

Maternal senescence is the detrimental effect of increased maternal age on offspring performance. Despite much recent interest given to describing this phenomenon, its distribution across animal species is poorly understood. A review of the published literature finds that maternal age affects pre-adult survival in 252 of 272 populations (93%) representing 97 animal species. Age effects tended to be deleterious in invertebrates and mammals, including humans, confirming the presence of senescence. However, bird species were a conspicuous exception, as pre-adult survival tended to increase with maternal age in surveyed populations. In all groups, maternal-age effects became more negative in older mothers. Invertebrates senesced faster than vertebrates, and humans aged faster than non-human mammals. Within invertebrates, lepidopterans demonstrated the most extreme rates of maternal-effect senescence. Among the surveyed studies, phylogeny, life history and environment (e.g. laboratory versus wild populations) were tightly associated; this made it difficult to make confident inferences regarding the causes of diversity for the phenomenon. However, we provide some testable suggestions, and we observe that some differences appear to be consistent with predictions from evolutionary theory. We discuss how future work may help clarify ultimate and proximate causes for this diversity.
Rhizobium rhizophilum sp. nov., an indole acetic acid-producing bacterium isolated from rape (Brassica napus L.) rhizosphere soil
Authors: Gao Jun-lian , Wang Li-wei , Xue Jing , Tong Shuai , Peng Guixiang , Sun Yu-chen , Zhang Xiuhai , Sun Jian-guang
Published: August 2020

A novel Gram-stain-negative, aerobic, rod-shaped and indole acetic acid-producing strain, designated 7209-2T, was isolated from rhizosphere of rape (Brassica napusL.) grown in the Yakeshi City, Inner Mongolia, PR China. The 16S rRNA gene sequence analysis indicated that strain 7209-2Tbelongs to the genusRhizobiumand is closely related toRhizobium rosettiformansW3T,Rhizobium ipomoeaeshin9-1TandRhizobium wuzhouenseW44Twith sequence similarities of 98.2, 98.1 and 97.9 %, respectively. Phylogenetic analysis based on concatenated housekeepingrecAandatpDgene sequences showed that strain 7209-2Tformed a group together withR. wuzhouenseW44TandR. rosettiformansW3T, with sequences similarities of 92.6 and 91.1 %, respectively. The genome size of strain 7209-2Twas 5.25 Mb, comprising 5027 predicted genes with a DNA G+C content of 61.2 mol%. The average nucleotide identity and digital DNA–DNA hybridization comparisons among 7209-2Tand reference strains for the most closely related species showed values below the accepted threshold for species discrimination. The major fatty acids of strain 7209-2Twere summed feature 8 (C18 : 1 ω7cand/or C18 : 1 ω6c) and summed feature 2 (C12 : 0aldehyde and/or unknown 10.953) . The major polar lipids were found to consist of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and an unidentified aminophospholipid. The predominant ubiquinone was identified as quinone 10. Based on all the above results, strain 7209-2Trepresents a novel species of the genusRhizobium, for which the nameRhizobium rhizophilumsp. nov. is proposed with 7209-2T(=CGMCC 1.15691T=DSM 103161T) as the type strain.
COVID-19 mild cases determination from correlating COVID-line calls to reported cases
Authors: Alvarez Ezequiel , Marsico Franco
Published: August 2020

One of the most challenging keys to understand COVID-19 evolution is to have a measure on those mild cases which are never tested because their few symptoms are soft and/or fade away soon. The problem is not only that they are difficult to identify and test, but also that it is believed that they may constitute the bulk of the cases and could be crucial in the pandemic equation. We present a novel and simple algorithm to extract the number of these mild cases by correlating a COVID-line phone calls to reported cases in given districts. The key assumption is to realize that, being a highly contagious disease, the number of calls by mild cases should be proportional to the number of reported cases. Whereas a background of calls not related to infected people should be proportional to the district population. We present the plain mathematics of the method and as a working example we apply it to Buenos Aires Province (Argentina), where it is being currently used. The implementation of this algorithm by other regions would be straightforward and would provide compelling information to the corresponding Health Care Administration.
The emergence of azithromycin-resistant Salmonella Typhi in Nepal
Authors: Duy Pham Thanh , Dongol Sabina , Giri Abhishek , Nguyen To Nguyen Thi , Ho Thanh Ngoc Dan , Nguyen Quynh Pham Nhu , Pham Trung Duc , Thwaites Guy E. , Basnyat Buddha , Baker Stephen , Rabaa Maia A. , Karkey Abhilasha
Published: August 2020

Typhoid fever remains a significant cause of morbidity and mortality in Asia and Africa. The emergence of azithromycin resistance in South Asia is concerning, as azithromycin is one of the last effective oral drugs for treating typhoid. In mid-2019, three azithromycin-resistant (AzithR) S. Typhi isolates were isolated from typhoid fever patients attending Patan Hospital, Kathmandu, Nepal. These organisms were whole genome sequenced and compared with a global collection. We found that the three AzithR isolates belonged to the H58 lineage and were genetically identical; they were distantly related to contemporaneous S. Typhi from Nepal and AzithRS. Typhi recently described in Bangladesh. Azithromycin resistance was mediated by nonsynonymous mutation in the acrB gene (R717L). Clinical information from one patient suggested non-response to azithromycin treatment. Further investigations are needed to evaluate treatment responses to azithromycin, predict AzithRS. Typhi’s evolutionary trajectories, and track the transmission of these organisms.
Seroprevalence of anti-SARS-CoV-2 IgG antibodies in children with household exposition to adults with COVID-19: preliminary findings
Authors: Buonsenso Danilo , Valentini Piero , De Rose Cristina , Pata Davide , Sinatti Dario , Speziale Domenico , Ricci Rosalba , Carfì Angelo , Landi Francesco , Sanguinetti Maurizio , Sali Michela ,   the Gemelli Against COVID-19 Post-Acute Care Study Group
Published: August 2020

Wheather children are easily susceptible to SARS-CoV-2 infection is still a debated question and a currently a hot topic, particularly in view of important decisions on school opening. For this reason, we decide to describe preliminary data showing the prevalence of anti-SARS-CoV-2 IgG in children with known household exposure to SARS-CoV-2.

Our report shows that household transmission of SARS-CoV-2 is high in both adults and children, with similar rates of SARS-CoV-2 IgG in all age groups, including the younger children. A total of 44 out of 80 household contacts (55%) of index patients had anti SARS-CoV-2 IgG. In particular, 16 (59,26%) adult partners had IgG antibodies compared with 28 (52,83%) of pediatric contacts (P > 0.05). Among the pediatric population, children ≥ 5 years of age had similar probability of having SARS-CoV-2 IgG (21/39, 53.8%) compared with those < 5 years (7/14, 50%) (P > 0.05). Adult partners and children also had a probability of having SARS-CoV-2 IgG. Interestingly, 35.7% of children and 33.3% of adults with SARS-CoV-2 IgG were previously diagnosed as COVID-19 cases.

Since this evidence of high rate of IgG in children exposed to SARS-CoV-2 has public health implication, with this comment we highlight the need of establishing appropriate guidelines for school opening and other social activities related to childhood.
Large-Scale Evaluation of the Positive and Negative Syndrome Scale (PANSS) Symptom Architecture in Schizophrenia
Authors: Lim Keane , Peh Oon-Him , Yang Zixu , Rekhi Gurpreet , Rapisarda Attilio , See Yuen-Mei , Rashid Nur Amirah Abdul , Ang Mei-San , Lee Sara-Ann , Sim Kang , Huang Hailiang , Lencz Todd , Lee Jimmy , Lam Max
Published: August 2020

Although the Positive and Negative Syndrome Scale (PANSS) is widely utilized in schizophrenia research, variability in specific item loading exist, hindering reproducibility and generalizability of findings across schizophrenia samples. We aim to establish a common metric PANSS factor structure from a large multi-ethnic sample and validate it against a meta-analysis of existing PANSS models. Schizophrenia participants (N = 3511) included in the current study were part of the Singapore Translational and Clinical Research Program (STCRP) and the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE). Exploratory Factor Analysis (EFA) was conducted to identify the factor structure of PANSS and validated with a meta-analysis (N = 16,171) of existing PANSS models. Temporal stability of the PANSS model and generalizability to individuals at ultra-high risk (UHR) of psychosis were evaluated. A five-factor solution best fit the PANSS data. These were the i) Positive, ii) Negative, iii) Cognitive/disorganization, iv) Depression/anxiety and v) Hostility factors. Convergence of PANSS symptom architecture between EFA model and meta-analysis was observed. Modest longitudinal reliability was observed. The schizophrenia derived PANSS factor model fit the UHR population, but not vice versa. We found that two other domains, Social Amotivation (SA) and Diminished Expression (DE), were nested within the negative symptoms factor. Here, we report one of the largest transethnic factorial structures of PANSS symptom domains (N = 19,682). Evidence reported here serves as crucial consolidation of a common metric PANSS that could aid in furthering our understanding of schizophrenia.
High prevalence of symptoms among Brazilian subjects with antibodies against SARS-CoV-2: a nationwide household survey
Authors: Menezes Ana M B , Victora Cesar G , Hartwig Fernando P , Silveira Mariângela F , Horta Bernardo L , Barros Aluísio J D , Mesenburg Marilia A , Whermeister Fernando C , Pellanda Lúcia C , Dellagostin Odir A , Struchiner Cláudio José , Burattini Marcelo N , Barros Fernando C , Hallal Pedro C
Published: August 2020

Since the beginning of the pandemic of COVID-19, there has been a widespread assumption that most infected persons are asymptomatic. A frequently-cited early study from China suggested that 86% of all infections were undocumented, which was used as indirect evidence that patients were asymptomatic.

Using data from the most recent wave of the EPICOVID19 study, a nationwide household-based survey including 133 cities from all states of Brazil, we estimated the proportion of people with and without antibodies for SARS-CoV-2 who were asymptomatic, which symptoms were most frequently reported, the number of symptoms reported and the association between symptomatology and socio-demographic characteristics. We were able to test 33,205 subjects using a rapid antibody test that was previously validated. Information on symptoms was collected before participants received the test result. Out of 849 (2.7%) participants who tested positive for SARS-CoV-2 antibodies, only 12.1% (95%CI 10.1-14.5) reported no symptoms since the start of the pandemic, compared to 42.2% (95%CI 41.7-42.8) among those who tested negative. The largest difference between the two groups was observed for changes in smell or taste (56.5% versus 9.1%, a 6.2-fold difference). Symptoms change in smell or taste, fever and myalgia were most likely to predict positive test results as suggested by recursive partitioning tree analysis.

Among individuals without any of these three symptoms (74.2% of the sample), only 0.8% tested positive, compared to 18.3% of those with both fever and changes in smell or taste. Most subjects with antibodies against SARS-CoV-2 in Brazil are symptomatic, even though most present only mild symptoms.
Optimal Closed-loop Deep Brain Stimulation with Multi-Contact Electrodes
Authors: Weerasinghe Gihan , Duchet Benoit , Bick Christian , Bogacz Rafal
Published: August 2020

Deep brain stimulation (DBS) is a well-established treatment option for a variety of neurological disorders, including Parkinson’s disease (PD) and essential tremor (ET). It is widely believed that the efficacy, efficiency and side-effects of the treatment can be improved by stimulating ‘closed-loop’, according to the symptoms of a patient. Multi-contact electrodes powered by independent current sources are a recent development in DBS technology which allow for greater precision when targeting one or more pathological regions but, in order to realise the potential of such systems, algorithms must be developed to deal with their increased complexity. This motivates the need to understand how applying DBS to multiple regions (or neural populations) can affect the efficacy and efficiency of the treatment. On the basis of a theoretical model, our paper aims to address the question of how to best apply DBS to multiple neural populations to maximally desynchronise brain activity. Using a coupled oscillator model, we derive analytical expressions which predict how the symptom severity should change as a result of applying stimulation. On the basis of these expressions we derive an algorithm describing when the stimulation should be delivered to individual contacts. Remarkably, these expressions also allow us to determine the conditions for when stimulation using information from individual contacts is likely to be advantageous. Using numerical simulation, we demonstrate that our methods have the potential to be both more effective and efficient than existing methods found in the literature.
FAIRSCAPE: A Framework for FAIR and Reproducible Biomedical Analytics
Authors: Levinson Maxwell Adam , Niestroy Justin , Manir Sadnan Al , Fairchild Karen , Lake Douglas E. , Moorman J. Randall , Clark Timothy
Published: August 2020

Results of computational analyses require transparent disclosure of their supporting resources, while the analyses themselves often can be very large scale and involve multiple processing steps separated in time. Evidence for the correctness of any analysis should include not only a textual description, but also a formal record of the computations which produced the result, including accessible data and software with runtime parameters, environment, and personnel involved.

This article describes FAIRSCAPE, a reusable computational framework, enabling simplified access to modern scalable cloud-based components. FAIRSCAPE fully implements the FAIR data principles and extends them to provide fully FAIR Evidence, including machine-interpretable provenance of datasets, software and computations, as metadata for all computed results.

The FAIRSCAPE microservices framework creates a complete Evidence Graph for every computational result, including persistent identifiers with metadata, resolvable to the software, computations, and datasets used in the computation; and stores a URI to the root of the graph in the result’s metadata. An ontology for Evidence Graphs, EVI (https://w3id.org/EVI), supports inferential reasoning over the evidence.

FAIRSCAPE can run nested or disjoint workflows and preserves provenance across them. It can run Apache Spark jobs, scripts, workflows, or user-supplied containers. All objects are assigned persistent IDs, including software. All results are annotated with FAIR metadata using the evidence graph model for access, validation, reproducibility, and re-use of archived data and software.
The contributions from the progenitor genomes of the mesopolyploid Brassiceae are evolutionarily distinct but functionally compatible
Authors: Hao Yue , Mabry Makenzie E. , Edger Patrick P. , Freeling Michael , Zheng Chunfang , Jin Lingling , VanBuren Robert , Colle Marivi , An Hong , Abrahams R. Shawn , Washburn Jacob D. , Qi Xinshuai , Barry Kerrie , Daum Christopher , Shu Shengqiang , Schmutz Jeremy , Sankoff David , Barker Michael S. , Lyons Eric , Pires J. Chris , Conant Gavin C.
Published: August 2020

The members of the tribe Brassiceae share a whole genome triplication (WGT), and one proposed model for its formation is a “two-step” pair of hybridizations producing hexaploid descendants. However, evidence for this model is incomplete, and the evolutionary and functional constraints that drove evolution after the hexaploidy are even less understood. Here we report a new genome sequence ofCrambe hispanica, a species sister to most sequenced Brassiceae. Using this new genome and three others that share the hexaploidy, we traced the history of gene loss after the WGT using POInT (the Polyploidy Orthology Inference Tool). We confirm the two-step formation model and infer that there was a significant temporal gap between those two allopolyploidizations, with about a third of the gene losses from the first two subgenomes occurring prior to the arrival of the third. We also, for the 90,000 individual genes in our study, make parental “subgenome” assignments, inferring, with measured uncertainty, which of the progenitor genomes of the allohexaploidy each gene derives from. We further show that each subgenome has a statistically distinguishable rate of homoeolog losses. There is little indication of functional distinction between the three subgenomes: the individual subgenomes show no patterns of functional enrichment, no excess of shared protein-protein or metabolic interactions between their members, and no biases in their likelihood of having experienced a recent selective sweep. We propose a “mix and match” model of allopolyploidy, where subgenome origin drives homoeolog loss propensities but where genes from different subgenomes function together without difficulty.
Phosphatidylserine prevents the generation of a protein-free giant plasma membrane domain in yeast
Authors: Mioka Tetsuo , Tian Guo , Shiyao Wang , Tsuji Takuma , Kishimoto Takuma , Fujimoto Toyoshi , Tanaka Kazuma
Published: August 2020

Membrane phase separation accompanied with micron-scale domains of lipids and proteins occurs in artificial membranes; however, a similar large phase separation has not been reported in the plasma membrane of the living cells. We demonstrate here that a stable micron-scale protein-free region is generated in the plasma membrane of the yeast mutants lacking phosphatidylserine. We named this region the “void zone”. Transmembrane proteins, peripheral membrane proteins, and certain phospholipids are excluded from the void zone. The void zone is rich in ergosterol and requires ergosterol and sphingolipids for its formation. These characteristics of the void zone are similar to the properties of the cholesterol-enriched domain in phase-separated artificial membranes. We propose that phosphatidylserine prevents the formation of the void zone by preferentially interacting with ergosterol. We also found that void zones were frequently in contact with vacuoles, in which a membrane domain was also formed at the contact site.

Summary statement

Yeast cells lacking phosphatidylserine generate protein-free plasma membrane domains, and vacuoles contact with this domain. This is the first report of micron-scale plasma membrane domains in living cells.
The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories
Authors: Liu Yang , Morgenstern Christian , Kelly James , Lowe Rachel ,   CMMID COVID-19 Working Group, Jit Mark
Published: August 2020

Introduction

Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories.

Methods

We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission with data from January - June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number (Rt) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in Rt, levels of NPI intensity, time-varying changes in NPI effect and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs.

Results

There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced Rt. Another three NPIs (workplace closure, income support and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g., restrictions on 1000+ people gathering were not effective, restrictions on <10 people gathering was). Evidence supporting the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs.

Conclusion

Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications taking into account these effects, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many although not all the actions policy-makers are taking to respond to the COVID-19 pandemic.
Histopathology of Third Trimester Placenta from SARS-CoV-2-Positive Women
Authors: He Mai , Skaria Priya , Kreutz Kasey , Chen Ling , Hagemann Ian , Carter Ebony B. , Mysorekar Indira U. , Nelson D Michael , Pfeifer John , Dehner Louis P.
Published: August 2020

Background

This study aims to investigate whether maternal SARS-CoV-2 status affect placental pathology.

Methods

A retrospective case-control study was conducted by reviewing charts and slides of placentas between April 1 to July 24, 2020. Clinical history of “COVID-19” were searched in Pathology Database (CoPath). Controls were matched with SARS-CoV-2-negative women with singleton deliveries in the 3rd-trimester. Individual and group, pathological features were extracted from placental pathology reports.

Results

Twenty-one 3rd-trimester, placentas from SARS-CoV-2-positive women were identified and compared to 20 placentas from SARS-CoV-2-negative women. There were no significant differences in individual or group gross or microscopic pathological features between the groups. Within the SARS-CoV-2+ group, there are no differences between symptomatic and asymptomatic women.

Conclusion

Placentas from SARS-CoV-2-positive women do not demonstrate a specific pathological pattern. Pregnancy complicated with COVID-19 during the 3rd trimester does not have a demonstrable effect on placental structure and pathology.
Moose or spruce: A systems analysis model for managing conflicts between moose and forestry in Sweden
Authors: Franklin Oskar , Krasovskiy Andrey , Kraxner Florian , Platov Anton , Schepaschenko Dmitry , Leduc Sylvain , Mattsson Brady
Published: August 2020

Sweden has the world’s highest density of moose (Alces alces). Moose is not only a valuable game species; it also causes forest damages and traffic accidents. To avoid moose browsing, foresters respond by planting spruce (Picea abies) to an extent that reshapes the forest landscape with impacts on both production and biodiversity. To address this problem and maintain a healthy moose population in balance with the other interests, an adaptive management based on the knowledge and experiences of local hunters and landowners is advocated. However, the different stakeholders do not agree on what is an appropriate moose population, which leads to conflicts that are hard to resolve. A key problem is that it is very difficult to encompass and foresee long-term consequences of different options for moose hunting and forest management. This makes it challenging to form coherent strategies that integrate different sectorial interests at a national level. To address this issue, we have developed a systems analysis framework for integrated modeling of the moose population, forestry, and their interactions and consequences for biodiversity. We analyze the short and long-term consequences for multiple scenarios of moose hunting and forest management. Based on the results we elucidate and quantify the trade-offs and possible synergies between moose hunting and forest production. This analysis can be used to support better informed and more constructive discussions among the stakeholders in the Swedish forest sectors, and to support policies for long term sustainable forest and moose management.
A single-cell method to map higher-order 3D genome organization in thousands of individual cells reveals structural heterogeneity in mouse ES cells
Authors: Arrastia Mary V. , Jachowicz Joanna W. , Ollikainen Noah , Curtis Matthew S. , Lai Charlotte , Quinodoz Sofia A. , Selck David A. , Guttman Mitchell , Ismagilov Rustem F.
Published: August 2020

In eukaryotes, the nucleus is organized into a three dimensional structure consisting of both local interactions such as those between enhancers and promoters, and long-range higher-order structures such as nuclear bodies. This organization is central to many aspects of nuclear function, including DNA replication, transcription, and cell cycle progression. Nuclear structure intrinsically occurs within single cells; however, measuring such a broad spectrum of 3D DNA interactions on a genome-wide scale and at the single cell level has been a great challenge. To address this, we developed single-cell split-pool recognition of interactions by tag extension (scSPRITE), a new method that enables measurements of genome-wide maps of 3D DNA structure in thousands of individual nuclei. scSPRITE maximizes the number of DNA contacts detected per cell enabling high-resolution genome structure maps within each cells and is easy-to-use and cost-effective. scSPRITE accurately detects chromosome territories, active and inactive compartments, topologically associating domains (TADs), and higher-order structures within single cells. In addition, scSPRITE measures cell-to-cell heterogeneity in genome structure at different levels of resolution and shows that TADs are dynamic units of genome organization that can vary between different cells within a population. scSPRITE will improve our understanding of nuclear architecture and its relationship to nuclear function within an individual nucleus from complex cell types and tissues containing a diverse population of cells.
Structural basis for VIPP1 oligomerization and maintenance of thylakoid membrane integrity
Authors: Gupta Tilak Kumar , Klumpe Sven , Gries Karin , Heinz Steffen , Wietrzynski Wojciech , Ohnishi Norikazu , Niemeyer Justus , Schaffer Miroslava , Rast Anna , Strauss Mike , Plitzko Jürgen M. , Baumeister Wolfgang , Rudack Till , Sakamoto Wataru , Nickelsen Jörg , Schuller Jan M. , Schroda Michael , Engel Benjamin D.
Published: August 2020

Vesicle-inducing protein in plastids (VIPP1) is essential for the biogenesis and maintenance of thylakoid membranes, which transform light into life. However, it is unknown how VIPP1 performs its vital membrane-shaping function. Here, we use cryo-electron microscopy to determine structures of cyanobacterial VIPP1 rings, revealing how VIPP1 monomers flex and interweave to form basket-like assemblies of different symmetries. Three VIPP1 monomers together coordinate a non-canonical nucleotide binding pocket that is required for VIPP1 oligomerization. Inside the ring’s lumen, amphipathic helices from each monomer align to form large hydrophobic columns, enabling VIPP1 to bind and curve membranes.In vivopoint mutations in these hydrophobic surfaces cause extreme thylakoid swelling under high light, indicating an essential role of VIPP1 lipid binding in resisting stress-induced damage. Our study provides a structural basis for understanding how the oligomerization of VIPP1 drives the biogenesis of thylakoid membranes and protects these life-giving membranes from environmental stress.
Cryo-EM Structures of the SARS-CoV-2 Endoribonuclease Nsp15
Authors: Pillon Monica C. , Frazier Meredith N. , Dillard Lucas B. , Williams Jason G. , Kocaman Seda , Krahn Juno M. , Perera Lalith , Hayne Cassandra K. , Gordon Jacob , Stewart Zachary D. , Sobhany Mack , Deterding Leesa J. , Hsu Allen L. , Dandey Venkata P. , Borgnia Mario J. , Stanley Robin E.
Published: August 2020

New therapeutics are urgently needed to inhibit SARS-CoV-2, the virus responsible for the on-going Covid-19 pandemic. Nsp15, a uridine-specific endoribonuclease found in all coronaviruses, processes viral RNA to evade detection by RNA-activated host defense systems, making it a promising drug target. Previous work with SARS-CoV-1 established that Nsp15 is active as a hexamer, yet how Nsp15 recognizes and processes viral RNA remains unknown. Here we report a series of cryo-EM reconstructions of SARS-CoV-2 Nsp15. The UTP-bound cryo-EM reconstruction at 3.36 Å resolution provides molecular details into how critical residues within the Nsp15 active site recognize uridine and facilitate catalysis of the phosphodiester bond, whereas the apo-states reveal active site conformational heterogeneity. We further demonstrate the specificity and mechanism of nuclease activity by analyzing Nsp15 products using mass spectrometry. Collectively, these findings advance understanding of how Nsp15 processes viral RNA and provide a structural framework for the development of new therapeutics.
Investigating molecular mechanisms of 2A-stimulated ribosomal pausing and frameshifting inTheilovirus
Authors: Hill Chris H. , Cook Georgia M. , Napthine Sawsan , Kibe Anuja , Brown Katherine , Caliskan Neva , Firth Andrew E. , Graham Stephen C. , Brierley Ian
Published: August 2020

The 2A protein of Theiler’s murine encephalomyelitis virus (TMEV) acts as a switch to stimulate programmed −1 ribosomal frameshifting (PRF) during infection. Here we present the X-ray crystal structure of TMEV 2A and define how it recognises the stimulatory RNA element. We demonstrate a critical role for bases upstream of the originally predicted stem-loop, providing evidence for a pseudoknot-like conformation and suggesting that the recognition of this pseudoknot by beta-shell proteins is a conserved feature in cardioviruses. Through examination of PRF in TMEV-infected cells by ribosome profiling, we identify a series of ribosomal pauses around the site of PRF induced by the 2A-pseudoknot complex. Careful normalisation of ribosomal profiling data with a 2A knockout virus facilitated the identification, through disome analysis, of ribosome stacking at the TMEV frameshifting signal. These experiments provide unparalleled detail of the molecular mechanisms underpinningTheilovirusprotein-stimulated frameshifting.
Discovery of a protein uptake pathway in lysosomes
Authors: Fujiwara Yuuki , Contu Viorica Raluca , Kabuta Chihana , Ogawa Megumu , Fujita Hiromi , Kikuchi Hisae , Sakai Ryohei , Hase Katsunori , Suzuki Mari , Koyama-Honda Ikuko , Inoue Michio , Oya Yasushi , Inoue Yukiko U. , Inoue Takayoshi , Takahashi Ryosuke , Nishino Ichizo , Wada Keiji , Noguchi Satoru , Kabuta Tomohiro
Published: August 2020

The degradation of cellular components plays an essential role in homeostasis. However, the known degradation pathways cannot account for the levels of proteolysis in cells. Here, we demonstrate that cytosolic proteins are imported into lysosomes in an ATP-dependent manner for degradation through a direct uptake mechanism distinct from any known pathway. SIDT2, a lysosomal membrane protein previously reported as an RNA transporter, translocates substrate proteins across the lysosomal membrane. Furthermore, we identify a dominant-negative mutation inSIDT2that causes neuropathy and distal myopathy with rimmed vacuoles, a protein aggregation disease in humans. We generateSidt2knockout mice, recapitulating the characteristic features of this disease. Our results reveal a novel degradation pathway and illustrate its crucial role in cellular proteostasis, physiology, and pathophysiology.

One Sentence Summary

Discovery of a novel proteolytic pathway in cells, the dysfunction of which leads to protein aggregation disease in humans.