bluuebunny/crossref_metadata_2025 huggingface dataset:
Logging residues for charcoal production through forest management in the Brazilian Amazon: economic gains and forest regrowth effects
Authors: Numazawa Camila T D , Krasovskiy Andrey , Kraxner Florian , Pietsch Stephan A
Published: September 2020

Sustainable forest management (SFM) practices can potentially reverse loss of forest cover due to deforestation, while concomitantly preserving and maintaining biodiversity, and stimulating jobs, income, and forest services. Recent studies found that significant logging residues (LR) (i.e. leaves, branches, and buttress roots) suitable for bioenergy production were often left in the felling area, triggering risks of forest fires and increased CO2 emissions due to wildfires or decomposition processes. For impact assessment of forest management practices, we collected primary harvesting data and estimated net primary productivity (NPP) and net ecosystem exchange (NEE) for 13 forest plots in the Brazilian Amazon. We applied a process-based forestry growth model (BGC-Man) to analyze the impacts on forest dynamics of selective logging and removal of LR, subject to landscape, soil texture, and daily weather. We explored the following selective logging scenarios: the Legal Reserve (i.e. reference) scenario, a scenario with one cutting cycle over the whole period, and a scenario with three timber rotation periods of 30 yr. Two of the later scenarios were complemented with harvesting of the woody LR (Ø ⩾ 10 cm) for charcoal production. For each scenario, we computed forest NPP and NEE over a 120 yr time horizon. Results suggest that using woody LR (i.e. 77% of total LR) for charcoal production would result in an economic gain equivalent to 24%–46% of the timber price. Our findings indicate that under scenarios where LR were removed, forest NPP recovered to the reference level and even higher, while income and jobs from harvesting LR for charcoal production were generated. We conclude that SFM could enhance forest productivity and deliver economic benefit from otherwise unexploited LR.
An analytical method to connect open curves for modeling protein-bound DNA minicircles
Authors: Sabok-Sayr Seyed A , Olson Wilma K
Published: September 2020

We introduce an analytical method to generate the pathway of a closed protein-bound DNA minicircle. We develop an analytical equation to connect two open curves smoothly and use the derived expressions to join the ends of two helical pathways and form models of nucleosome-decorated DNA minicircles. We find that the simplest smooth connector which satisfies the boundary conditions at the end points and the length requirement for such connections to be a quartic function on the xy-plane and linear along the z-direction. This is a general method which can be used to connect any two open curves with well defined mathematical definitions as well as pairs of discrete systems found experimentally. We used this method to describe the configurations of torsionally relaxed, 360-base pair DNA rings with two evenly-spaced, ideal nucleosomes. We considered superhelical nucleosomal pathways with different levels of DNA wrapping and allowed for different inter-nucleosome orientations. We completed the DNA circles with the smooth connectors and studied the associated bending and electrostatic energies for different configurations in the absence and presence of salt. The predicted stable states bear close resemblance to reconstituted minicircles observed under low and high salt conditions.
Cubic interactions of arbitrary spin fields in 3d flat space
Authors: Metsaev R R
Published: September 2020

Using light-cone gauge formulation, massive arbitrary spin irreducible fields and massless (scalar and spin one-half) fields in three-dimensional flat space are considered. Both the integer spin and half-integer spin fields are studied. For such fields, we provide classification for cubic interactions and obtain explicit expressions for all cubic interaction vertices. We study two forms of the cubic interaction vertices which we refer to as first-derivative form and higher-derivative form. All cubic interaction vertices are built by using the first-derivative form.
Real-time breath ammonia measurement using a novel cuprous bromide sensor device in patients with chronic liver disease: a feasibility and pilot study
Authors: Ishida Jinya , Oikawa Tsunekazu , Nakagawa Chika , Takano Keiko , Fujioka Kouki , Kikuchi Yoshio , Tsuboi Osamu , Ueda Kaoru , Nakano Masanori , Saeki Chisato , Torisu Yuichi , Ikeda Yuichi , Saruta Masayuki , Tsubota Akihito
Published: September 2020

We developed a small portable sensor device using a p-type semiconductor cuprous bromide (CuBr) thin film to measure breath ammonia in real time with highsensitivity and selectivity. Breath ammonia is reportedly associated with chronic liver disease (CLD). We aimed to assess the practical utility of the novel CuBr sensor device for exhaled breath ammonia and the correlation between breath and blood ammonia in CLD patients. This was a feasibility and pilot clinical study of 21 CLD patients and 18 healthy volunteers. Breath ammonia was directly and quickly measured using the novel CuBr sensor device and compared with blood ammonia measured at the same time. CLD patients had significantly higher breath ammonia levels than healthy subjects (p = 1.51 × 10−3), with the level of significance being similar to that for blood ammonia levels (p= 0.024). Significant differences were found in breath and blood ammonia between the healthy and cirrhosis groups (p = 2.97 × 10−3 and 3.76 × 10−3, respectively). Significant, positive correlations between breath and blood ammonia were noted in the CLD group (R = 0.747, p = 1.00 × 10−4), healthy/CLD group (R = 0.741, p = 6.75 × 10−8), and cirrhosis group (R = 0.744, p = 9.52 × 10−4). In conclusion, the newly developed, easy-to-use, and small portable CuBr sensor device was able to non-invasively measure breath ammonia in real time. Breath ammonia measured using the device was correlated with blood ammonia and the presence of liver cirrhosis, and might be an alternative surrogate biomarker to blood ammonia.
Impact of breath sampling on exhaled carbon monoxide
Authors: Ghorbani Ramin , Blomberg Anders , Schmidt Florian M
Published: September 2020

The influence of breath sampling on exhaled carbon monoxide (eCO) and related pulmonary gas exchange parameters is investigated in a study with 32 healthy non-smokers. Mid-infrared tunable diode laser absorption spectroscopy and well-controlled online sampling is used to precisely measure mouth- and nose-exhaled CO expirograms at exhalation flow rates (EFRs) of 250, 120 and 60 ml s−1, and for 10 s of breath-holding followed by exhalation at 120 ml s−1. A trumpet model with axial diffusion is employed to fit simulated exhalation profiles to the experimental expirograms, which provides equilibrium airway and alveolar CO concentrations and the average lung diffusing capacity in addition to end-tidal concentrations. For all breathing maneuvers, excellent agreement is found between mouth- and nose-exhaled end-tidal CO (ETCO), and the individual values for ETCO and alveolar diffusing capacity are consistent across maneuvers. The eCO parameters clearly show a dependence on EFR, where the lung diffusing capacity increases with EFR, while ETCO slightly decreases. End-tidal CO is largely independent of ambient air CO and alveolar diffusing capacity. While airway CO is slightly higher than, and correlates strongly with, ambient air CO, and there is a weak correlation with ETCO, the results point to negligible endogenous airway CO production in healthy subjects. An EFR of around 120 ml s−1 can be recommended for clinical eCO measurements. The employed method provides means to measure variations in endogenous CO, which can improve the interpretation of exhaled CO concentrations and the diagnostic value of eCO tests in clinical studies.

Clinical trial registration number: 2017/306-31
Verbal Short-Form FSIQ Estimations for Possible Use With Individuals With Motor and Visual Impairment or in Virtual Environments
Authors: Merz Zachary C , Lace John W , Garcia Julian
Published: September 2020

Objective

Abbreviated and virtual neuropsychological assessment practices are growing in popularity and viable alternatives to traditional testing methods are needed, especially in the face of global health concerns. This study generated and examined short form (SF) full-scale IQ (FSIQ) estimations, which lend themselves to virtual test administration.

Methods

Archival data were procured from 318 concurrent cognitive evaluations at a university clinic. Twenty-six unique SF combinations, including dyads, triads, tetrads, and pentads, were created from Wechsler Adult Intelligence Scale, 4th edition (WAIS-IV) subtests within verbal comprehension and working memory indices due to these tests’ ability to be administered without visual stimuli or psychomotor involvement.

Results

Stepwise regression analyses revealed 9 SF combinations (i.e., 1 pentad, 3 tetrads, 2 triads, and 3 dyads) that significantly accounted for unique variance in FSIQ scores and provided good accuracy estimating FSIQ.

Conclusion

Results suggest the potential viability of verbal WAIS-IV SF FSIQ estimations for clinical use when assessing patients with motor or visual impairments, as well as performing tele-neuropsychological services.
A computational toolset for rapid identification of SARS-CoV-2, other viruses and microorganisms from sequencing data
Authors: Chen Shifu , He Changshou , Li Yingqiang , Li Zhicheng , Melançon Charles E
Published: September 2020

In this paper, we present a toolset and related resources for rapid identification of viruses and microorganisms from short-read or long-read sequencing data. We present fastv as an ultra-fast tool to detect microbial sequences present in sequencing data, identify target microorganisms and visualize coverage of microbial genomes. This tool is based on the k-mer mapping and extension method. K-mer sets are generated by UniqueKMER, another tool provided in this toolset. UniqueKMER can generate complete sets of unique k-mers for each genome within a large set of viral or microbial genomes. For convenience, unique k-mers for microorganisms and common viruses that afflict humans have been generated and are provided with the tools. As a lightweight tool, fastv accepts FASTQ data as input and directly outputs the results in both HTML and JSON formats. Prior to the k-mer analysis, fastv automatically performs adapter trimming, quality pruning, base correction and other preprocessing to ensure the accuracy of k-mer analysis. Specifically, fastv provides built-in support for rapid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identification and typing. Experimental results showed that fastv achieved 100% sensitivity and 100% specificity for detecting SARS-CoV-2 from sequencing data; and can distinguish SARS-CoV-2 from SARS, Middle East respiratory syndrome and other coronaviruses. This toolset is available at: https://github.com/OpenGene/fastv.
Inhibitory control dysfunction in parkinsonian impulse control disorders
Authors: Meyer Garance M , Spay Charlotte , Beliakova Alina , Gaugain Gabriel , Pezzoli Gianni , Ballanger Bénédicte , Boulinguez Philippe , Cilia Roberto
Published: September 2020

Impulse control disorders (ICDs) in Parkinson’s disease have been associated with dysfunctions in the control of value- or reward-based responding (choice impulsivity) and abnormalities in mesocorticolimbic circuits. The hypothesis that dysfunctions in the control of response inhibition (action impulsivity) also play a role in Parkinson’s disease ICDs has recently been raised, but the underlying neural mechanisms have not been probed directly. We used high-resolution EEG recordings from 41 patients with Parkinson’s disease with and without ICDs to track the spectral and dynamical signatures of different mechanisms involved in inhibitory control in a simple visuomotor task involving no selection between competing responses and no reward to avoid potential confounds with reward-based decision. Behaviourally, patients with Parkinson’s disease with ICDs proved to be more impulsive than those without ICDs. This was associated with decreased beta activity in the precuneus and in a region of the medial frontal cortex centred on the supplementary motor area. The underlying dynamical patterns pinpointed dysfunction of proactive inhibitory control, an executive mechanism intended to gate motor responses in anticipation of stimulation in uncertain contexts. The alteration of the cortical drive of proactive response inhibition in Parkinson’s disease ICDs pinpoints the neglected role the precuneus might play in higher order executive functions in coordination with the supplementary motor area, specifically for switching between executive settings. Clinical perspectives are discussed in the light of the non-dopaminergic basis of this function.
A Randomized, Placebo-controlled, Double-blind Pilot Study of Single-dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa loa Infection
Authors: Legrand Fanny , Herrick Jesica , Makiya Michelle , Ramanathan Roshan , Thompson Reagan , Rampertaap Shakuntala , Stoddard Jennifer , Ware JeanAnne , Fay Michael P , Holland-Thomas Nicole , Nutman Thomas B , Klion Amy D
Published: September 2020

Background

Diethylcarbamazine citrate (DEC) treatment of loiasis is complicated by adverse reactions that are correlated with the number of circulating microfilariae (mf). The cause of these reactions is unknown, but they are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation.

Methods

To explore the role of IL-5 driven eosinophilia in post-DEC reactions, 8 adults with confirmed loiasis and <5000 mf/mL blood were enrolled in a randomized, double-blind, placebo-controlled trial of the humanized anti-IL-5 antibody, reslizumab, (1.0 mg/kg IV) administered 3 to 7 days prior to initiation of DEC treatment (9 mg/kg/day for 21 days). The primary endpoint was the reduction in absolute eosinophil count (AEC) during the first week of DEC treatment.

Results

Baseline characteristics were comparable between the two groups. Single dose reslizumab lowered the AEC by 77% prior to initiation of DEC therapy (vs. 12% in the placebo group, P < .05). More importantly, AEC remained below baseline in the first week of DEC treatment in all subjects who received reslizumab and in none of the placebo subjects. Mf clearance occurred within 2 days of initiation of DEC in all 7 mf-positive subjects. Mild to moderate adverse events were seen in all 8 subjects and were not significantly different between the groups.

Conclusions

In summary, although reslizumab was able to blunt peripheral eosinophilia post-DEC treatment in subjects with loiasis and had no effect on microfilarial clearance, the reduction in AEC appeared to have been insufficient to prevent post-treatment AEs.
Validation of the European Society of Cardiology pre-test probability model for obstructive coronary artery disease
Authors: Winther Simon , Schmidt Samuel Emil , Rasmussen Laust Dupont , Juárez Orozco Luis Eduardo , Steffensen Flemming Hald , Bøtker Hans Erik , Knuuti Juhani , Bøttcher Morten
Published: September 2020

Aims 

Estimation of pre-test probability (PTP) of disease in patients with suspected coronary artery disease (CAD) is a common challenge. Due to decreasing prevalence of obstructive CAD in patients referred for diagnostic testing, the European Society of Cardiology suggested a new PTP (2019-ESC-PTP) model. The aim of this study was to validate that model.

Methods and results 

Symptomatic patients referred for coronary computed tomography angiography (CTA) due to suspected CAD in a geographical uptake area of 3.3 million inhabitants were included. The reference standard was a combined endpoint of CTA and invasive coronary angiography (ICA) with obstructive CAD defined at ICA as a ≥50% diameter stenosis or fractional flow reserve ≤0.80 when performed. The 2019-ESC-PTP, 2013-ESC-PTP, and CAD Consortium basic PTP scores were calculated based on age, sex, and symptoms. Of the 42 328 identified patients, coronary stenosis was detected in 8.8% using the combined endpoint. The 2019-ESC-PTP and CAD Consortium basic scores classified substantially more patients into the low PTP groups (PTP < 15%) than did the 2013-ESC-PTP (64% and 65% vs. 16%, P < 0.001). Using the combined endpoint as reference, calibration of the 2019-ESC-PTP model was superior to the 2013-ESC-PTP and CAD Consortium basic score.

Conclusion 

The new 2019-ESC-PTP model is well calibrated and superior to the previously recommended models in predicting obstructive stenosis detected by a combined endpoint of CTA and ICA.
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1): a crucial driver of atherosclerotic cardiovascular disease
Authors: Akhmedov Alexander , Sawamura Tatsuya , Chen Chu-Huang , Kraler Simon , Vdovenko Daria , Lüscher Thomas F
Published: September 2020

Cardiovascular diseases (CVDs), specifically lipid-driven atherosclerotic CVDs, remain the number one cause of death worldwide. The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a scavenger receptor that promotes endothelial dysfunction by inducing pro-atherogenic signalling and plaque formation via the endothelial uptake of oxidized LDL (oxLDL) and electronegative LDL, contributes to the initiation, progression, and destabilization of atheromatous plaques, eventually leading to the development of myocardial infarction and certain forms of stroke. In addition to its expression in endothelial cells, LOX-1 is expressed in macrophages, cardiomyocytes, fibroblasts, dendritic cells, lymphocytes, and neutrophils, further implicating this receptor in multiple aspects of atherosclerotic plaque formation. LOX-1 holds promise as a novel diagnostic and therapeutic target for certain CVDs; therefore, understanding the molecular structure and function of LOX-1 is of critical importance. In this review, we highlight the latest scientific findings related to LOX-1, its ligands, and their roles in the broad spectrum of CVDs. We describe recent findings from basic research, delineate their translational value, and discuss the potential of LOX-1 as a novel target for the prevention, diagnosis, and treatment of related CVDs.
Economic evaluation of an absorbable antibiotic envelope for prevention of cardiac implantable electronic device infection
Authors: Rennert-May Elissa , Raj Satish R , Leal Jenine , Exner Derek V , Manns Braden J , Chew Derek S
Published: September 2020

Aims

Recent evidence suggests that an antibiotic impregnated envelope inserted at time of cardiac implantable electronic device (CIED) implantation may reduce risk of subsequent CIED infection compared with standard of care (SoC). The objective of the current work was to perform a cost-effectiveness analysis comparing an antibiotic impregnated envelope with SoC at time of CIED insertion.

Methods and results

Decision analytic models were used to project healthcare costs and benefits of two strategies, an antibiotic impregnated envelope plus SoC (Env+SoC) vs. SoC alone, in a cohort of patients undergoing CIED implantation over a 1-year time horizon. Evidence from published literature informed the model inputs. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was the incremental cost per infection prevented, assessed from the Canadian healthcare system perspective. Envelope plus SoC was associated with fewer CIED infection (7 CIED infections/1000 patients) at higher total costs ($29 033 000/1000 patients) compared with SoC (11 CIED infections and $27 926 000/1000 patients). The incremental cost per infection prevented over 1 year was $274 416. Use of Env+SoC was cost saving only when baseline CIED infection risk was increased to 6% (vs. base case of 1.2%).

Conclusions

A strategy of Env+SoC was not economically favourable compared with SoC alone, and the opportunity cost of widescale implementation should be considered. Future work is required to develop validated risk stratification tools to identify patients at greatest risk of CIED infection. The value proposition of Env+SoC improves when applying this intervention to patients at greatest infection risk.
Biallelic variants in the small optic lobe calpain CAPN15 are associated with congenital eye anomalies, deafness and other neurodevelopmental deficits
Authors: Zha Congyao , Farah Carole A , Holt Richard J , Ceroni Fabiola , Al-Abdi Lama , Thuriot Fanny , Khan Arif O , Helaby Rana , Lévesque Sébastien , Alkuraya Fowzan S , Kraus Alison , Ragge Nicola K , Sossin Wayne S
Published: September 2020

Microphthalmia, coloboma and cataract are part of a spectrum of developmental eye disorders in humans affecting ~12 per 100 000 live births. Currently, variants in over 100 genes are known to underlie these conditions. However, at least 40% of affected individuals remain without a clinical genetic diagnosis, suggesting variants in additional genes may be responsible. Calpain 15 (CAPN15) is an intracellular cysteine protease belonging to the non-classical small optic lobe (SOL) family of calpains, an important class of developmental proteins, as yet uncharacterized in vertebrates. We identified five individuals with microphthalmia and/or coloboma from four independent families carrying homozygous or compound heterozygous predicted damaging variants in CAPN15. Several individuals had additional phenotypes including growth deficits, developmental delay and hearing loss. We generated Capn15 knockout mice that exhibited similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth. We demonstrate widespread Capn15 expression throughout the brain and central nervous system, strongest during early development, and decreasing postnatally. Together, these findings demonstrate a critical role of CAPN15 in vertebrate developmental eye disorders, and may signify a new developmental pathway.
Evaluating popular online English-Chinese dictionaries in China by applying Lew and Szarowska’s (2017) evaluation framework
Authors: Liu Dilin , Deng Yaochen , Yang Shiyan
Published: September 2020

By applying Lew and Szarowska’s (2017) evaluation framework and methodology (with a few methodological enhancements made), this study evaluated six popular online English-Chinese dictionaries in China and produced some useful findings. First, Lew and Szarowska’s framework and methodology proved very successful in this study, demonstrating their viability in evaluating online bilingual dictionaries, although a few aspects where enhancements could be made were also identified. Second, the results of the evaluation of the six dictionaries in comparison with those from Lew and Szarowska (2017) suggest that while online dictionaries in the past few years seemed to have made improvements in some areas (e.g. increased coverage of lexical items including neologisms, technical words, and multiword expressions), they appeared to have shown little improvement with problems in some other areas (e.g. inadequate provision of usage, English variety, and part of speech labels and some inappropriate example sentences). Suggestions for addressing the existing problems are provided and implications for future research are discussed.
Factors influencing family member perspectives on safety in the intensive care unit: a systematic review
Authors: Coombs M A , Statton S , Endacott C V , Endacott R
Published: September 2020

Purpose

Patient safety has developed as a strong marker for healthcare quality. Safety matters are important in the intensive care unit (ICU) where complex clinical decisions are made, intensive technology is used, and families hold a unique role. The aim of this review was to identify and describe factors that influence family member’s perceptions of safety in the adult ICU.

Data sources

Searches were conducted between September and November 2018 and repeated in July 2020 using CINAHL, MEDLINE (EBSCO), PubMed and PsycINFO databases.

Study selection

Published primary studies undertaken in adult ICUs and involving adult family member participants exploring safety or feeling safe. No date restrictions were applied.

Data extraction

A data extraction form collected information about sample, study design, data collection methods and results from each paper. Methodological quality was assessed using the QualSyst tools for qualitative and quantitative studies. Narrative synthesis was undertaken.

Results of data synthesis

Twenty papers were included with 11 papers published since 2010. The majority of papers reported on qualitative studies (n = 16). Four factors were identified that influenced whether family members felt that the patient was safe in ICU: family visiting, information and communication, caring and professional competence.

Conclusion

In detailing specific practices that make families feel safe and unsafe in ICU, these review findings provide a structure for clinicians, educators and researchers to inform future work and gives opportunity for the family role in patient safety to be reconsidered.
Contemporary use of real-world data for clinical trial conduct in the United States: a scoping review
Authors: Rogers James R , Lee Junghwan , Zhou Ziheng , Cheung Ying Kuen , Hripcsak George , Weng Chunhua
Published: September 2020

Objective

Real-world data (RWD), defined as routinely collected healthcare data, can be a potential catalyst for addressing challenges faced in clinical trials. We performed a scoping review of database-specific RWD applications within clinical trial contexts, synthesizing prominent uses and themes.

Materials and Methods

Querying 3 biomedical literature databases, research articles using electronic health records, administrative claims databases, or clinical registries either within a clinical trial or in tandem with methodology related to clinical trials were included. Articles were required to use at least 1 US RWD source. All abstract screening, full-text screening, and data extraction was performed by 1 reviewer. Two reviewers independently verified all decisions.

Results

Of 2020 screened articles, 89 qualified: 59 articles used electronic health records, 29 used administrative claims, and 26 used registries. Our synthesis was driven by the general life cycle of a clinical trial, culminating into 3 major themes: trial process tasks (51 articles); dissemination strategies (6); and generalizability assessments (34). Despite a diverse set of diseases studied, <10% of trials using RWD for trial process tasks evaluated medications or procedures (5/51). All articles highlighted data-related challenges, such as missing values.

Discussion

Database-specific RWD have been occasionally leveraged for various clinical trial tasks. We observed underuse of RWD within conducted medication or procedure trials, though it is subject to the confounder of implicit report of RWD use.

Conclusion

Enhanced incorporation of RWD should be further explored for medication or procedure trials, including better understanding of how to handle related data quality issues to facilitate RWD use.
The technology behind TB DEPOT: a novel public analytics platform integrating tuberculosis clinical, genomic, and radiological data for visual and statistical exploration
Authors: Long Alyssa , Glogowski Alexander , Meppiel Matthew , De Vito Lisa , Engle Eric , Harris Michael , Ha Grace , Schneider Darren , Gabrielian Andrei , Hurt Darrell E , Rosenthal Alex
Published: September 2020

Objective

Clinical research informatics tools are necessary to support comprehensive studies of infectious diseases. The National Institute of Allergy and Infectious Diseases (NIAID) developed the publicly accessible Tuberculosis Data Exploration Portal (TB DEPOT) to address the complex etiology of tuberculosis (TB).

Materials and Methods

TB DEPOT displays deidentified patient case data and facilitates analyses across a wide range of clinical, socioeconomic, genomic, and radiological factors. The solution is built using Amazon Web Services cloud-based infrastructure, .NET Core, Angular, Highcharts, R, PLINK, and other custom-developed services. Structured patient data, pathogen genomic variants, and medical images are integrated into the solution to allow seamless filtering across data domains.

Results

Researchers can use TB DEPOT to query TB patient cases, create and save patient cohorts, and execute comparative statistical analyses on demand. The tool supports user-driven data exploration and fulfills the National Institute of Health’s Findable, Accessible, Interoperable, and Reusable (FAIR) principles.

Discussion

TB DEPOT is the first tool of its kind in the field of TB research to integrate multidimensional data from TB patient cases. Its scalable and flexible architectural design has accommodated growth in the data, organizations, types of data, feature requests, and usage. Use of client-side technologies over server-side technologies and prioritizing maintenance have been important lessons learned. Future directions are dynamically prioritized and key functionality is shared through an application programming interface.

Conclusion

This paper describes the platform development methodology, resulting functionality, benefits, and technical considerations of a clinical research informatics application to support increased understanding of TB.
Temperament influences mitochondrial capacity in skeletal muscle from 8 through 18 mo of age in Brahman heifers
Authors: Owen Randi N , Latham Christine M , Long Charles R , Randel Ronald D , Welsh Thomas H , White-Springer Sarah H
Published: September 2020

Temperamental cattle tend to yield carcasses of poorer quality, and Brahman cattle are reportedly more temperamental than non-indicus cattle breeds. A potential link between temperament and product quality may be mitochondrial activity. We hypothesized that mitochondrial measures would be greater in temperamental compared with calm heifers and that the relationships between temperament and mitochondria would persist as heifers age. Serum cortisol and skeletal muscle (longissimus thoracis [LT] and trapezius [TRAP]) mitochondrial profiles and antioxidant activities were quantified from the same calm (n = 6) and temperamental (n = 6) Brahman heifers at 8, 12, and 18 mo of age. Data were analyzed using a mixed model ANOVA in SAS (9.4) with repeated measures. Serum cortisol was greater in temperamental compared with calm heifers throughout the study (P = 0.02). Mitochondrial volume density (citrate synthase [CS] activity) increased over time (P < 0.0001) but was similar between temperament and muscle groups. Mitochondrial function (cytochrome c oxidase activity) was greatest in the temperamental LT at 8 mo of age (P ≤ 0.0006), greatest in the temperamental TRAP at 18 mo of age (P ≤ 0.003), and did not differ by temperament at 12 mo of age. Integrative (relative to tissue wet weight) mitochondrial oxidative phosphorylation capacity with complex I substrates (PCI), PCI plus complex II substrate (PCI+II), noncoupled electron transfer system capacity (ECI+II), and E with functional complex II only (ECII) were greater in the TRAP than LT for calm heifers at all ages (P ≤ 0.002), but were similar between muscle groups in temperamental heifers. Overall, calm heifers tended to have greater intrinsic (relative to CS activity) PCI and flux control of PCI+II (P ≤ 0.1) than temperamental heifers, indicating greater utilization of complex I paired with greater coupling efficiency in calm heifers. Within the LT, integrative PCI+II was greater (P = 0.05) and ECI+II tended to be greater (P = 0.06) in temperamental compared with calm heifers. From 8- to 18-mo old, glutathione peroxidase (GPx) activity decreased (P < 0.0001) and superoxide dismutase activity increased (P = 0.02), and both were similar between muscle groups. The activity of GPx was greater in temperamental compared with calm heifers at 8 (P = 0.004) but not at 12 or 18 mo of age. These results detail divergent skeletal muscle mitochondrial characteristics of live Brahman heifers according to temperament, which should be further investigated as a potential link between temperament and product quality.
Tenebrio molitor (Coleoptera: Tenebrionidae)—Optimization of Rearing Conditions to Obtain Desired Nutritional Values
Authors: Adámková Anna , Mlček Jiří , Adámek Martin , Borkovcová Marie , Bednářová Martina , Hlobilová Veronika , Knížková Ivana , Juríková Tunde
Published: September 2020

The present study dealt with the influence of temperature and feed on the nutritional value of Tenebrio molitor, especially on the content of crude protein, amino acids, fat, and fatty acid profile. Tenebrio molitor larvae were kept in 15, 20, and 25°C and fed with wheat bran, lentil flour, and mixture. The parameters were analyzed by international standard methods. Generally, with an increase of the lentils in the feed, the crude protein content increased. The changes in the temperature and the feed were most pronounced on the essential amino acids Val, Arg, and Leu. The highest average fat content was determined at 20°C in insects fed with wheat bran. The lowest fat content was determined at 15°C in bran-fed insects. The dependency of fat content on the temperature in feeding with lentil flour and a mixture of wheat bran and lentil flour was statistically insignificant (P > 0.05, Kruskal–Wallis, Mann–Whitney post hoc tests). The highest content of polyene fatty acids was achieved at a rearing temperature of 15°C and the bran diet. It was concluded that a higher proportion of protein diet could increase the content of crude protein in the insects. An increase in the temperature generally leads only to a slight increase in the content of nitrogenous substances. The influence of feed on this nutritional parameter is therefore much more significant than the effect of the rearing temperature. In general, it can be stated that the feed and the temperature also significantly affect the fat content.
Phase I studies of darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma: a pooled analysis of two phase I studies conducted in Japan and Korea
Authors: Ogura Michinori , Kim Won-Seog , Uchida Toshiki , Uike Naokuni , Suehiro Youko , Ishizawa Kenichi , Nagai Hirokazu , Nagahama Fumiko , Sonehara Yusuke , Tobinai Kensei
Published: September 2020

Objective

Two phase I studies of darinaparsin including Japanese and Korean patients with relapsed/refractory peripheral T-cell lymphoma were performed to evaluate its safety (primary purpose), efficacy and pharmacokinetic profile (ClinicalTrials.gov: NCT01435863 and NCT01689220).

Methods

Patients received intravenous darinaparsin for 5 consecutive days at 200 mg/m2/day in 4-week cycles, 300 mg/m2/day in 4-week cycles or 300 mg/m2/day in 3-week cycles.

Results

Seventeen Japanese and 6 Korean patients were enrolled and treated. Drug-related adverse events developed in 18 patients (78%). Dose-limiting toxicity, grade 3 hepatic dysfunction, was reported on Day 15 of cycle 1 in 1 Japanese patient who received 300 mg/m2/day. The most common drug-related, grade ≥ 3 adverse events were lymphopenia (9%), neutropenia (9%) and thrombocytopenia (9%). No deaths occurred. In 14 evaluable patients, 1 and 3 patients had complete response and partial response, respectively. The plasma concentration-time profiles of arsenic, a surrogate marker for darinaparsin, were similar between Japanese and Korean patients. No significant difference was found in its pharmacokinetic profile.

Conclusions

These data indicate the good tolerability and potential efficacy of darinaparsin in patients with relapsed/refractory peripheral T-cell lymphoma. Darinaparsin 300 mg/m2/day for 5 consecutive days in 3-week cycles is the recommended regimen for phase II study.
Crisis in Psychiatric Diagnosis? Epistemological Humility in the DSM Era
Authors: Kinghorn Warren
Published: September 2020

The modern editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), beginning with DSM-III in 1980, emerged in response to notable challenges to psychiatry’s practices and ways of knowing in the early 1970s. Because these challenges threatened psychiatry’s scientific self-understanding and moral authority, they exemplify what Alasdair MacIntyre has termed “epistemological crisis.” As a response to crisis, the modern DSM has been a stunning political achievement, providing the central diagnostic constructs around which psychiatric research, practice, and reimbursement has been organized for four decades. Indeed, the DSM’s authority survives in the face of ongoing trenchant scientific and philosophical critique. But if psychiatry is to be healthy, it must be epistemologically humble, reckoning honestly with the limits of the DSM before a future epistemological crisis destabilizes it entirely.
What is the reproductive number of yellow fever?
Authors: Liu Ying , Rocklöv Joacim
Published: September 2020

Teaser Our review found the average reproductive number R0 for yellow fever to be 4.81 with a median of 4.21.
Classical term-modal logics
Authors: Frijters Stef , Van De Putte Frederik
Published: September 2020

We introduce classical term-modal logics and argue that they are useful for modelling agent-relative notions of obligation, evidence and abilities, and their interaction with properties of and relations between the agents in question. We spell out the semantics of these logics in terms of neighborhood models, provide sound and strongly complete axiomatizations and establish the decidability of specific (agent-finite) variants.
Modeling legal conflict resolution based on dynamic logic
Authors: Ju Fengkui , Nygren Karl , Xu Tianwen
Published: September 2020

Conflicts between legal norms are common in reality. In many legislations, legal conflicts between norms are resolved by applying ordered principles. This work presents a formalization of the conflict resolution mechanism and introduces action legal logic ($\textsf{ALL}$) to reason about the normative consequences of possibly conflicting legal systems. The semantics of $\textsf{ALL}$ is explicitly based on legal systems consisting of norms and ordered principles. Legal systems specify the legal status of transitions in transition systems and the language of $\textsf{ALL}$ describes the legal status of paths in transition systems. The formalization is used to study abstract revisions of legal systems. The expressivity of $\textsf{ALL}$ is studied and its completeness is proved.
Impact of intrinsic polarization of Sgr A* historical flares on (polarization) properties of their X-ray echoes
Authors: Khabibullin Ildar , Churazov Eugene , Sunyaev Rashid
Published: September 2020

Reflection of X-ray emission on molecular clouds in the inner ∼100 pc of our Galaxy reveals that, despite being extremely quiet at the moment, our supermassive black hole Sgr A* should have experienced bright flares of X-ray emission in the recent past. Thanks to the improving characterization of the reflection signal, we are able to infer parameters of the most recent flare(s) (age, duration, and luminosity) and relative line-of-sight disposition of the brightest individual molecular complexes. We show that combining these data with measurements of polarization in the reflected X-ray continuum will not only justify Sgr A* as the primary source but also allow deriving intrinsic polarization properties of the flare emission. This will help to identify radiation mechanisms and underlying astrophysical phenomena behind them. For the currently brightest reflecting molecular complex, Sgr A, the required level of sensitivity might be already accessible with upcoming X-ray polarimeters.
Measuring the spectral index of turbulent gas with deep learning from projected density maps
Authors: Trevisan Piero , Pasquato Mario , Ballone Alessandro , Mapelli Michela
Published: September 2020

Turbulence plays a key role in star formation in molecular clouds, affecting star cluster primordial properties. As modelling present-day objects hinges on our understanding of their initial conditions, better constraints on turbulence can result in windfalls in Galactic archaeology, star cluster dynamics, and star formation. Observationally, constraining the spectral index of turbulent gas usually involves computing spectra from velocity maps. Here, we suggest that information on the spectral index might be directly inferred from column density maps (possibly obtained by dust emission/absorption) through deep learning. We generate mock density maps from a large set of adaptive mesh refinement turbulent gas simulations using the hydro-simulation code ramses. We train a convolutional neural network (CNN) on the resulting images to predict the turbulence index, optimize hyperparameters in validation and test on a holdout set. Our adopted CNN model achieves a mean squared error of 0.024 in its predictions on our holdout set, over underlying spectral indexes ranging from 3 to 4.5. We also perform robustness tests by applying our model to altered holdout set images, and to images obtained by running simulations at different resolutions. This preliminary result on simulated density maps encourages further developments on real data, where observational biases and other issues need to be taken into account.
Origin and Evolution of the Gene Family of Proteinaceous Pheromones, the Exocrine Gland-Secreting Peptides, in Rodents
Authors: Niimura Yoshihito , Tsunoda Mai , Kato Sari , Murata Ken , Yanagawa Taichi , Suzuki Shunta , Touhara Kazushige
Published: September 2020

The exocrine-gland secreting peptide (ESP)gene family encodes proteinaceous pheromones that are recognized by the vomeronasal organ in mice. For example, ESP1 is a male pheromone secreted in tear fluid that regulates socio-sexual behavior, and ESP22 is a juvenile pheromone that suppresses adult sexual behavior. The family consists of multiple genes and has been identified only in mouse and rat genomes. The coding region of a mouse ESP gene is separated into two exons, each encoding signal and mature sequences. Here, we report the origin and evolution of the ESP gene family. ESP genes were found only in the Muridea and Cricetidae families of rodents, suggesting a recent origin of ESP genes in the common ancestor of murids and cricetids. ESP genes show a great diversity in number, length, and sequence among different species as well as mouse strains. Some ESPs in rats and golden hamsters are expressed in the lacrimal gland and the salivary gland. We also found that a mature sequence of an ESP gene showed overall sequence similarity to the α-globin gene. The ancestral ESP gene seems to be generated by recombination of a retrotransposed α-globin gene with the signal-encoding exon of the CRISP2 gene located adjacent to the ESP gene cluster. This study provides an intriguing example of molecular tinkering in rapidly evolving species-specific proteinaceous pheromone genes.
Log Transformation Improves Dating of Phylogenies
Authors: Mai Uyen , Mirarab Siavash
Published: September 2020

Phylogenetic trees inferred from sequence data often have branch lengths measured in the expected number of substitutions and therefore, do not have divergence times estimated. These trees give an incomplete view of evolutionary histories since many applications of phylogenies require time trees. Many methods have been developed to convert the inferred branch lengths from substitution unit to time unit using calibration points, but none is universally accepted as they are challenged in both scalability and accuracy under complex models. Here, we introduce a new method that formulates dating as a nonconvex optimization problem where the variance of log-transformed rate multipliers is minimized across the tree. On simulated and real data, we show that our method, wLogDate, is often more accurate than alternatives and is more robust to various model assumptions.
CoreCruncher: Fast and Robust Construction of Core Genomes in Large Prokaryotic Data Sets
Authors: Harris Connor D , Torrance Ellis L , Raymann Kasie , Bobay Louis-Marie
Published: September 2020

The core genome represents the set of genes shared by all, or nearly all, strains of a given population or species of prokaryotes. Inferring the core genome is integral to many genomic analyses, however, most methods rely on the comparison of all the pairs of genomes; a step that is becoming increasingly difficult given the massive accumulation of genomic data. Here, we present CoreCruncher; a program that robustly and rapidly constructs core genomes across hundreds or thousands of genomes. CoreCruncher does not compute all pairwise genome comparisons and uses a heuristic based on the distributions of identity scores to classify sequences as orthologs or paralogs/xenologs. Although it is much faster than current methods, our results indicate that our approach is more conservative than other tools and less sensitive to the presence of paralogs and xenologs. CoreCruncher is freely available from: https://github.com/lbobay/CoreCruncher. CoreCruncher is written in Python 3.7 and can also run on Python 2.7 without modification. It requires the python library Numpy and either Usearch or Blast. Certain options require the programs muscle or mafft.
eIF2α interactions with mRNA control accurate start codon selection by the translation preinitiation complex
Authors: Thakur Anil , Gaikwad Swati , Vijjamarri Anil K , Hinnebusch Alan G
Published: September 2020

In translation initiation, AUG recognition triggers rearrangement of the 48S preinitiation complex (PIC) from an open conformation to a closed state with more tightly-bound Met-tRNAi. Cryo-EM structures have revealed interactions unique to the closed complex between arginines R55/R57 of eIF2α with mRNA, including the −3 nucleotide of the ‘Kozak’ context. We found that R55/R57 substitutions reduced recognition of a UUG start codon at HIS4 in Sui− cells (Ssu− phenotype); and in vitro, R55G-R57E accelerated dissociation of the eIF2·GTP·Met-tRNAi ternary complex (TC) from reconstituted PICs with a UUG start codon, indicating destabilization of the closed complex. R55/R57 substitutions also decreased usage of poor-context AUGs in SUI1 and GCN4 mRNAs in vivo. In contrast, eIF2α-R53 interacts with the rRNA backbone only in the open complex, and the R53E substitution enhanced initiation at a UUG codon (Sui− phenotype) and poor-context AUGs, while reducing the rate of TC loading (Gcd− phenotype) in vivo. Consistently, R53E slowed TC binding to the PIC while decreasing TC dissociation at UUG codons in vitro, indicating destabilization of the open complex. Thus, distinct interactions of eIF2α with rRNA or mRNA stabilize first the open, and then closed, conformation of the PIC to influence the accuracy of initiation in vivo.