bluuebunny/crossref_metadata_2025 huggingface dataset:
SEPIC - MPPT controller with photovoltaic energy for groundwater extraction
Authors: Corzo C L , Núñez R A , Flórez J I , Rodríguez P A , Plata K J
Published: July 2021

The model-based design methodology is presented for the development of an experimental SEPIC-MPPT controller powered by a photovoltaic module, designed to extract water from a deep well using a DC submersible motor pump. To specify the proposed methodology, a photovoltaic panel was characterized under various conditions of solar radiation and the modeling of its Voltage-Current relationship was carried out. The best tilt angle for the installation was determined to be nine degrees (9°). Similarly, a SEPIC controller was developed from model-based design. The results obtained showed an average adjustment error of less than 4%, on the performance parameters contrasted in the modeled / experimental system. The efficiency achieved by the SEPIC-MPPT controller was 85.26%. It is concluded that the methodology implemented for the design is coherent and valid for the development of SEPIC-MPPT controllers with application in underground water extraction systems, in areas with photovoltaic potential.
Extraction of Humic Acids from Different Origins: A Review
Authors: Quiroz-Urzola H , Castro-Suarez J R , Colpas-Castillo F
Published: July 2021

The synthesis of molecules such as humic acids is a good strategy for the remediation of eroded soils. Since the synthesis and extraction of these carbon molecules do not represent a process of energy liberation of the carbon, it is also a low-cost process. Bad practices in soils, such as the indiscriminate use of pesticides and pesticides, cause damage to the soil that can be difficult to reverse, depending on the type of exposure and resilience they have. For example, the Atlantic coast is the most affected by salinization, according to Ideam a phenomenon related to incorrect agricultural activities, devastating tourism, and the impact of the dry climate. Soil erosion is an effect that has a negative influence on activities such as agriculture since the erosion of the soils prevents or causes the agricultural activity to be low or almost nil. Humic acids are molecules that can retain cations in their macroporous structure. Therefore, it is important to study what is the affinity that these macromolecules have with the cations of Zn, Ca, K, Mg and therefore, to know with which of them the affinity is greater depending on the type of carbon studied. The objective of this monographic study is to review the conceptual part of humic acids, their different forms of extraction, and their applications reported by different authors working in this field.
Portable Device for Continuous Measurement (DIPORMEC)
Authors: Rodriguez-Arias H.A.
Published: July 2021

Nowadays, the conditions of the workplace are having a very important role in different areas. Therefore, a device was created to measure variables, for the time being, of quantity, of light, Lumens and Lux, temperature and relative humidity. Besides, this device continuously saves these variables in a file on an SD card to be analysed later. Another feature of this device is that it is portable which means it works with built-in batteries or with a universal connector, so that it can work easily in a workplace (offices). For this work it is shown how what we call cloning of the luminosity sensor was performed, for this particular case, with an LDR the amount of Lux is determined, taking as reference the light sensor of the Samsung A7 cell phone, and thus generating the equation that governs the sensor. In the connection diagram, the possibility of connecting other sensors that do not require adjustment work such as the one of brightness is left open, taking full advantage of the Arduino card’s capacity, but for the moment it is not part of the study of this work.
Radial distribution Systems solving in GAMS - Practice Implementation
Authors: Rojas-Martinez L A , Montoya OD , Martinez-Trespalacios J A , Rojas C. , Pacheco C. , Castro-Suarez john R.
Published: July 2021

In the following work, the practical implementation of a radial distribution system will be carried out. This work is done in the GAMS software. In the present work the analysis will be carried out to three radial systems of 10, 33, 69 nodes. In which it is expected to analyze the best location of distributed generation systems (GD) and batteries (B), in order to obtain an objective function (Z) that represent the best performance of each system. The systems have a single source of generation and will be assigned Distributed Generators and Batteries. In the same way taking into account the variation of the systems, it is expected to analyze the active power losses, the reactive power losses, the power of the battery and the charge state of the battery in a period of 24 hours. The analysis was done with the GAMS software.
Teaching equipment of newton’s second law
Authors: Gallego Becerra Hugo Armando , García Sebastián Martínez , Henao Melo Luis Guillermo
Published: July 2021

Mechanic is the branch of physics that is responsible for the study of the movement and balance of bodies in a system, within this can also be considered the bodies at rest. For the first case the scientist Isaac Newton considered the study of the movement of bodies, where he defines that any physical system which is subjected to different actions, as long as such actions are not nullified, will result in a change in the state of the body. The force is the magnitude that quantitatively measures the intensity, direction and direction of that interactions, having said that, if the summation of all forces of a system is different from zero, it can be concluded that the system will be in motion and therefore have an associated acceleration. Based on the above definition, was executed by the research group Design and Construction of Prototypes for Demonstration Experiments (DICOPED) in the design and construction of a prototype that allows to verify the Newton’s Second Law, looking to develop an autonomous, robust and low-cost prototype, that allows the use of the technology and tools present in the means, encourage and facilitate the teaching of basic concepts but no less important of physics to students of basic and higher education.
Enhanced thermal sensitivity in single metal thermocouple: significance of thickness-engineering of the metal layers
Authors: Mulla Rafiq , Dunnill Charles W
Published: July 2021

Single metal thermocouples (SMTs) have recently been developed with a new design concept of width-engineering of metal segments. In such designs, two segments of different micro-width are formed to obtain different levels of Seebeck effects. The variations in the Seebeck effect achieved from dissimilar segment width are small. In addition, the fabrication of such micro-width patterns requires special fabrication facilities such as photolithography or electron-beam lithography. In this paper, an alternative method is presented that has the potential to give high thermal sensing SMTs and requires no sophisticated facilities to fabricate. The method is based on thickness-engineering instead of width-engineering, and thus devices can be obtained from commonly available thin film deposition techniques. Constructing better thermal sensing SMTs is possible with this approach as thickness can be easily and conveniently varied down to nanoscale range which is necessary to achieve significant changes in the Seebeck effects from effectively utilizing size effects. As a result, a high thermal sensing bismuth based-SMT has been fabricated with a sensitivity of as high as 31 μV K−1, one of the highest values reported for SMTs. It is straightforward, more convenient over width-engineering approach and thus SMTs can be easily developed.
Symmetric and antisymmetric kernels for machine learning problems in quantum physics and chemistry
Authors: Klus Stefan , Gelß Patrick , Nüske Feliks , Noé Frank
Published: July 2021

We derive symmetric and antisymmetric kernels by symmetrizing and antisymmetrizing conventional kernels and analyze their properties. In particular, we compute the feature space dimensions of the resulting polynomial kernels, prove that the reproducing kernel Hilbert spaces induced by symmetric and antisymmetric Gaussian kernels are dense in the space of symmetric and antisymmetric functions, and propose a Slater determinant representation of the antisymmetric Gaussian kernel, which allows for an efficient evaluation even if the state space is high-dimensional. Furthermore, we show that by exploiting symmetries or antisymmetries the size of the training data set can be significantly reduced. The results are illustrated with guiding examples and simple quantum physics and chemistry applications.
Myomegalin regulates Hedgehog pathway by controlling PDE4D at the centrosome
Authors: Peng Hualing , Zhang Jingyi , Ya Amanda , Ma Winston , Villa Sammy , Sukenik Shahar , Ge Xuecai
Published: July 2021

The phosphodiesterase PDE4D3 is tethered to the centrosome by Myomegalin (Mmg), a centrosome scaffold protein. Mmg loss dislocates PDE4D3 from the centrosome, leading to local PKA overactivation and inhibition of the Hedgehog signaling without interfering with other PKA-related cell signaling. Mmg loss blocks the growth of medulloblastoma in mouse model.
Platypnoea-orthodeoxia syndrome in an older patient with COVID-19 pneumonia and orthostatic hypotension—a case of prolonged hospital admission
Authors: Ismail Muhammad Azam , Trevest Katie
Published: July 2021

An 89-year-old woman was admitted to hospital with a fall, general malaise and low oxygen saturations. She tested positive for SARS-CoV-2 and commenced on standard therapy for COVID-19 pneumonia. She improved initially but reported ongoing dyspnoea exacerbated by position. Following investigations to rule out other causes, she was given a diagnosis of platypnoea-orthodeoxia syndrome (POS). She was treated with gradual verticalization therapy with supplemental oxygen and subsequently discharged to an intermediate care bed (ICB).
Withdrawn as duplicate: Evaluation of discharge prescribing after rescheduling of gabapentin as a controlled substance
Authors: Robbins Melody J , Floroff Catherine , Ingemi Amanda , Kaplan Marcus C
Published: July 2021

This article has been withdrawn due to a publisher error that caused the article to be duplicated. The definitive version of this article is published under DOI 10.1093/ajhp/zxab293.
Differential Response in Ethanol Behaviors of Female Rats Given Various Weight Loss Surgeries
Authors: Orellana Elise R , Piscura Mary K , Horvath Nelli , Hajnal Andras
Published: July 2021

Aims

Currently, the only effective treatment for morbid obesity and its comorbidities is weight loss surgery (WLS). Growing evidence suggests that different types of WLS, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), have differential effects on alcohol consumption in humans and rats. Thus, we aimed to directly compare the effects of these two surgical procedures, for the first time in female rats, and to determine whether presence or absence of the ghrelin-producing stomach tissue has critical influence on postoperative alcohol intake.

Methods

We performed two experiments using an identical behavioral protocol, a continuous-access two-bottle choice protocol for various concentrations of ethanol (EtOH). In Experiment 1, 23 high fat diet (HFD) obese, female rats were randomized to three groups: RYGB, SG or sham-operated food-restricted (Sham) controls. In Experiment 2, HFD obese female rats received either sham (n = 11) or a modified RYGB surgery where the remnant stomach was removed (RYGB-X; n = 12).

Results

SG rats drank significantly less than RYGB for 4, 6 and 8% and significantly less than Sham for 6, 8 and 8% reinstatement. RYGB-X consumed significantly less EtOH than Sham across all concentrations, reaching significance for 6 and 8% reinstatement.

Conclusion

These findings confirm reduced EtOH consumption by female SG rats as opposed to increased intake following RYGB, and provide the first experimental evidence that the remnant stomach in the RYGB procedure is contributory. Future studies in rats and humans are warranted to confirm that ghrelin plays a critical role in susceptibility to AUD development following WLS.
A Multivariate Interpretation of the Spanish-Language NIH Toolbox Cognition Battery: The Normal Frequency of Low Scores
Authors: Karr Justin E , Mindt Monica Rivera , Iverson Grant L
Published: July 2021

Objective

The current study involved the preparation of multivariate base rates for the Spanish-language NIH Toolbox Cognition Battery (NIHTB-CB) based on the U.S. normative sample, quantifying the normal frequency of low scores among healthy adults.

Method

Participants included 250 healthy Latinx adults (M = 38.8 ± 13.7 years old, range: 19–80; 72.0% women; education: M = 11.5 ± 3.9 years) who completed the full Spanish-language NIHTB-CB, including two tests of crystallized cognition and five tests of fluid cognition. Multivariate base rates quantified the frequency at which participants obtained 1 or more fluid scores ≤25th, ≤16th, ≤9th, ≤5th, and ≤2nd percentile, per age-adjusted or demographically adjusted (age, gender, education) normed scores.

Results

A substantial minority of participants had 1 or more low scores (e.g., 40.4% had 1 or more age-adjusted score ≤16th percentile). The frequencies of low scores increased with fewer years of education and lower crystallized cognitive ability. Higher frequencies of low scores were observed among participants who were born and educated abroad, versus within the USA; monolingual Spanish speakers, versus bilingual Spanish/English speakers; and from households below the national median income, versus households above the national median.

Conclusion

Low scores were common and related to crystallized ability, education, and sociocultural variables. Although using demographically adjusted scores reduced group differences related to sociocultural variables, group differences were not eliminated, indicating that age, gender, and education score adjustments do not fully explain the associations between sociocultural variables and test performances. These stratified base rates may be useful when working with Spanish-speaking patients with diverse sociocultural characteristics.
Inhibition of GFAT1 in lung cancer cells destabilizes PD-L1 protein
Authors: Chen Wenshu , Saxton Bryanna , Tessema Mathewos , Belinsky Steven A
Published: July 2021

Immunotherapy using checkpoint blockers (antibodies) has been a major advance in recent years in the management of various types of solid cancers including lung cancer. One target of checkpoint blockers is programmed death ligand 1 (PD-L1) expressed by cancer cells, which engages programmed death 1 on T cells and Natural Killer (NK) cells resulting in suppression of their activation and cancer-killing function, respectively. Apart from antibodies, other clinically relevant agents that can inhibit PD-L1 are limited. PD-L1 protein stability depends on its glycosylation. Here we show that l-glutamine:d-fructose-6-phosphate amidotransferase 1 (GFAT1), a rate-limiting enzyme of the hexosamine biosynthesis pathway, which produces uridine diphosphate-N-acetyl-β-glucosamine, a precursor for glycosylation, is required for the stability of PD-L1 protein. Inhibition of GFAT1 activity markedly reduced interferon gamma (IFNγ)-induced PD-L1 levels in various lung cancer cell lines. GFAT1 inhibition suppressed glycosylation of PD-L1 and accelerated its proteasomal degradation. Importantly, inhibition of GFAT1 in IFNγ-treated cancer cells enhanced the activation of T cells and the cancer-killing activity of NK cells. These findings support using GFAT1 inhibitors to manipulate PD-L1 protein level that could augment the efficacy of immunotherapy for lung cancer.
Total Content of Piperidine Analysis in Artane by RP-HPLC Using Pre-Column Derivatization with 4-Toluene Sulfonyl Chloride
Authors: Zhou Guiyin , Chen Yao , Tang Ying
Published: July 2021

A simple, sensitive and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method was established for the determination of piperidine and piperidine hydrochloride in artane, using pre-column derivatization with 4-toluenesulfonyl chloride. The RP-HPLC method was carried out on a Inertsil C18 column (250 × 4.6 mm I.D.) maintained at 30°C. The mobile phase consisted of water with 0.1% phosphoric acid (phase A) and acetonitrile (phase B) (32:68, V:V) at a flow rate of 1.0 mL/min. Linearity of piperidine was found in the range of 0.44–53.33 μg/mL with R2 = 0.9996. The limit of detection was estimated to be 0.15 μg/mL, and the limit of quantitation was 0.44 μg/mL. The average recovery was 101.82% with relative standard deviations of 0.6% at three spiked levels. The developed method using HPLC-ultraviolet system was a rapid tool for routine analysis of piperidine in the bulk form with good accuracy.
Anogenital Human Papillomavirus (HPV) Infection, Seroprevalence, and Risk Factors for HPV Seropositivity Among Sexually Active Men Enrolled in a Global HPV Vaccine Trial
Authors: Tota Joseph E , Giuliano Anna R , Goldstone Stephen E , Dubin Brady , Saah Alfred , Luxembourg Alain , Velicer Christine , Palefsky Joel M
Published: July 2021

Background

In men, the incidence of human papillomavirus (HPV)–related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries.

Methods

This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus–negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type.

Results

Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4–6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM.

Conclusions

Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut.

Clinical Trials Registration. NCT00090285.
External validation of a high-sensitive troponin I algorithm for rapid evaluation of acute myocardial infarction in a Danish cohort
Authors: Andersen Camilla Fuchs , Bang Camilla , Lauridsen Kasper Glerup , Frederiksen Christian Alcaraz , Schmidt Morten , Jensen Tage , Hornung Nete , Løfgren Bo
Published: July 2021

Aims

An accelerated diagnostic algorithm for ruling-in or ruling-out myocardial infarction (MI) after 1 hour (1 h) has recently been derived and internally validated for the Siemens ADVIA Centaur TNIH assay. We aimed to validate the diagnostic performance of the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in a Danish cohort.

Methods and results

Patients with chest pain suggestive of MI were prospectively enrolled. High-sensitive troponin I (TNIH) was measured at admission (0 h) and after 30 minutes (30 m), 1 h, and 3 hours (3 h). We externally validated the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in Danish patients. Moreover, we applied the algorithm using the second TNIH measurement at 30 m instead of 1 h. We enrolled 1003 patients: median (Q1–Q3) age 64 (52–74) years, 42% female, and 23% with previous MI. Myocardial infarction was the final diagnosis in 9% of patients. Median (Q1–Q3) times from admission to 30 m and 1 h blood draw were 35 min (30–37 min) and 67 min (62–75 min), respectively. Using the 0 h and 1 h results, 468 (47%) patients were assigned to rule-out, 104 (10%) to rule-in, and 431 (43%) to the observational zone. This resulted in a negative predictive value of 100% (95% confidence interval: 99.2–100%), sensitivity of 100% (95.9–100%), positive predictive value of 79.8 (70.8–87.0%), and specificity of 97.7% (96.5–98.6%). The diagnostic performance after 30 m was similar.

Conclusions

The TNIH 0 h/1 h algorithm ad modum Boeddinghaus performed excellently for rule-out of MI in a Danish cohort. The Boeddinghaus algorithm also performed excellently after only 30 m.

Trial registration number

NCT03634384.

Trial registry name and URL

Rapid Use of High-Sensitive Cardiac Troponin I for Ruling-in and Ruling-out Acute Myocardial Infarction (RACING-MI), https://clinicaltrials.gov/ct2/show/NCT03634384.
Spectrum bias in algorithms derived by artificial intelligence: a case study in detecting aortic stenosis using electrocardiograms
Authors: Tseng Andrew S , Shelly-Cohen Michal , Attia Itzhak Z , Noseworthy Peter A , Friedman Paul A , Oh Jae K , Lopez-Jimenez Francisco
Published: July 2021

Aims

Spectrum bias can arise when a diagnostic test is derived from study populations with different disease spectra than the target population, resulting in poor generalizability. We used a real-world artificial intelligence (AI)-derived algorithm to detect severe aortic stenosis (AS) to experimentally assess the effect of spectrum bias on test performance.

Methods and results

All adult patients at the Mayo Clinic between 1 January 1989 and 30 September 2019 with transthoracic echocardiograms within 180 days after electrocardiogram (ECG) were identified. Two models were developed from two distinct patient cohorts: a whole-spectrum cohort comparing severe AS to any non-severe AS and an extreme-spectrum cohort comparing severe AS to no AS at all. Model performance was assessed. Overall, 258 607 patients had valid ECG and echocardiograms pairs. The area under the receiver operator curve was 0.87 and 0.91 for the whole-spectrum and extreme-spectrum models, respectively. Sensitivity and specificity for the whole-spectrum model was 80% and 81%, respectively, while for the extreme-spectrum model it was 84% and 84%, respectively. When applying the AI-ECG derived from the extreme-spectrum cohort to patients in the whole-spectrum cohort, the sensitivity, specificity, and area under the curve dropped to 83%, 73%, and 0.86, respectively.

Conclusion

While the algorithm performed robustly in identifying severe AS, this study shows that limiting datasets to clearly positive or negative labels leads to overestimation of test performance when testing an AI algorithm in the setting of classifying severe AS using ECG data. While the effect of the bias may be modest in this example, clinicians should be aware of the existence of such a bias in AI-derived algorithms.
Absolute and relative risk prediction in cardiovascular primary prevention with a modified SCORE chart incorporating ceramide-phospholipid risk score and diabetes mellitus
Authors: Hilvo Mika , Jylhä Antti , Lääperi Mitja , Jousilahti Pekka , Laaksonen Reijo
Published: July 2021

Aims

A risk score, CERT2, based on distinct ceramide and phosphatidylcholine lipid species, has shown robust performance in predicting cardiovascular risk in secondary prevention. Here, our aim was to investigate the predictive value of CERT2 in primary prevention compared to classical lipid biomarkers and its compatibility with clinical characteristics used in the SCORE risk chart.

Methods and results

Four ceramides [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] and three phosphatidylcholines [PC(14:0/22:6), PC(16:0/22:5), PC(16:0/16:0)] were analysed by targeted tandem liquid chromatography–mass spectrometry method in FINRISK 2002, which is a population-based risk factor survey investigating men and women aged 25–74 years. Primary prevention subjects (N = 7324) were followed up for 10 years for the following outcomes: incident coronary heart disease (CHD), cardiovascular disease (CVD), major adverse cardiovascular event (MACE), stroke, and heart failure. Hazard ratios per standard deviation obtained from adjusted Cox proportional hazard models were significant for all these endpoints, and the highest for fatal ones, i.e. fatal CHD [1.45 (95% confidence interval 1.07–1.97)], CVD [1.39 (1.06–1.83)], and MACE [1.39 (1.07–1.80)]. The categorical net reclassification improvement was 0.051 for the 10-year risk of incident CVD. Incidence of fatal events was over 10-fold more frequent in the highest CERT2 category compared to the lowest risk category and modified SCORE risk charts, utilizing CERT2 and diabetes mellitus, increased granularity of risk assessment compared to a chart utilizing total cholesterol.

Conclusion

CERT2 is a significant predictor of incident cardiovascular outcomes and risk charts utilizing this score provide an easy tool to estimate relative and absolute risk for incident CVD.
De novo genome assembly of the marine teleost, bluefin trevally (Caranx melampygus)
Authors: Pickett Brandon D , Glass Jessica R , Ridge Perry G , Kauwe John S K
Published: July 2021

The bluefin trevally, Caranx melampygus, also known as the bluefin kingfish or bluefin jack, is known for its remarkable, bright-blue fins. This marine teleost is a widely prized sportfish, but few resources have been devoted to the genomics and conservation of this species because it is not targeted by large-scale commercial fisheries. Population declines from recreational and artisanal overfishing have been observed in Hawai‘i, USA, resulting in both an interest in aquaculture and concerns about the long-term conservation of this species. Most research to-date has been performed in Hawai‘i, raising questions about the status of bluefin trevally populations across its Indo-Pacific range. Genomic resources allow for expanded research on stock status, genetic diversity, and population demography. We present a high quality, 711 Mb nuclear genome assembly of a Hawaiian bluefin trevally from noisy long-reads with a contig NG50 of 1.2 Mb and longest contig length of 8.9 Mb. As measured by single-copy orthologs, the assembly was 95% complete, and the genome is comprised of 16.9% repetitive elements. The assembly was annotated with 33.1 K protein-coding genes, 71.4% of which were assigned putative functions, using RNA-seq data from eight tissues from the same individual. This is the first whole-genome assembly published for the carangoid genus Caranx. Using this assembled genome, a multiple sequentially Markovian coalescent model was implemented to assess population demography. Estimates of effective population size suggest population expansion has occurred since the Late Pleistocene. This genome will be a valuable resource for comparative phylogenomic studies of carangoid fishes and will help elucidate demographic history and delineate stock structure for bluefin trevally populations throughout the Indo-Pacific.
Accuracy of GEBV of sires based on pooled allele frequency of their progeny
Authors: Vargas Jurado Napoleón , Kuehn Larry A , Keele John W , Lewis Ronald M
Published: July 2021

Despite decreasing genotyping costs, in some cases individually genotyping animals is not economically feasible (e.g., in small ruminants). An alternative is to pool DNA, using the pooled allele frequency (PAF) to garner information on performance. Still, the use of PAF for prediction (estimation of genomic breeding values; GEBVs) has been limited. Two potential sources of error on accuracy of GEBV of sires, obtained from PAF of their progeny themselves lacking pedigree information, were tested: (i) pool construction error (unequal contribution of DNA from animals in pools), and (ii) technical error (variability when reading the array). Pooling design (random, extremes, K-means), pool size (5, 10, 25, 50, and 100 individuals), and selection scenario (random, phenotypic) also were considered. These factors were tested by simulating a sheep population. Accuracy of GEBV—the correlation between true and estimated values—was not substantially affected by pool construction or technical error, or selection scenario. A significant interaction, however, between pool size and design was found. Still, regardless of design, mean accuracy was higher for pools of 10 or less individuals. Mean accuracy of GEBV was 0.174 (SE 0.001) for random pooling, and 0.704 (SE 0.004) and 0.696 (SE 0.004) for extreme and K-means pooling, respectively. Non-random pooling resulted in moderate accuracy of GEBV. Overall, pooled genotypes can be used in conjunction with individual genotypes of sires for moderately accurate predictions of their genetic merit with little effect of pool construction or technical error.
Efficient construction of a linkage map and haplotypes for Mentha suaveolens using sequence capture
Authors: Tsai Helen , Kippes Nestor , Firl Alana , Lieberman Meric , Comai Luca , Henry Isabelle M
Published: July 2021

The sustainability of many crops is hindered by the lack of genomic resources and a poor understanding of natural genetic diversity. Particularly, application of modern breeding requires high-density linkage maps that are integrated into a highly contiguous reference genome. Here, we present a rapid method for deriving haplotypes and developing linkage maps, and its application to Mentha suaveolens, one of the diploid progenitors of cultivated mints. Using sequence-capture via DNA hybridization to target single nucleotide polymorphisms (SNPs), we successfully genotyped ∼5000 SNPs within the genome of >400 individuals derived from a self cross. After stringent quality control, and identification of nonredundant SNPs, 1919 informative SNPs were retained for linkage map construction. The resulting linkage map defined a total genetic space of 942.17 cM divided among 12 linkage groups, ranging from 56.32 to 122.61 cM in length. The linkage map is in good agreement with pseudomolecules from our preliminary genome assembly, proving this resource effective for the correction and validation of the reference genome. We discuss the advantages of this method for the rapid creation of linkage maps.
Engineering threshold-based selection systems
Authors: Pedone Katherine H , González-Pérez Vanessa , Leopold Luciana E , Rasmussen Neal R , Der Channing J , Cox Adrienne D , Ahmed Shawn , Reiner David J
Published: July 2021

Using model organisms to identify novel therapeutic targets is frequently constrained by pre-existing genetic toolkits. To expedite positive selection for identification of novel downstream effectors, we engineered conditional expression of activated CED-10/Rac to disrupt Caenorhabditis elegans embryonic morphogenesis, titrated to 100% lethality. The strategy of engineering thresholds for positive selection using experimental animals was validated with pharmacological and genetic suppression and is generalizable to diverse molecular processes and experimental systems.
Differences in temperature-sensitive expression of PcG-regulated genes among natural populations of Drosophila melanogaster
Authors: Voigt Susanne , Kost Luise
Published: July 2021

Environmental temperature can affect chromatin-based gene regulation, in particular in ectotherms such as insects. Genes regulated by the Polycomb group (PcG) vary in their transcriptional output in response to changes in temperature. Expression of PcG-regulated genes typically increases with decreasing temperatures. Here, we examined variations in temperature-sensitive expression of PcG target genes in natural populations from different climates of Drosophila melanogaster, and differences thereof across different fly stages and tissues. Temperature-induced expression plasticity was found to be stage- and sex-specific with differences in the specificity between the examined PcG target genes. Some tissues and stages, however, showed a higher number of PcG target genes with temperature-sensitive expression than others. Overall, we found higher levels of temperature-induced expression plasticity in African tropical flies from the ancestral species range than in flies from temperate Europe. We also observed differences between temperate flies, however, with more reduction of expression plasticity in warm-temperate than in cold-temperate populations. Although in general, temperature-sensitive expression appeared to be detrimental in temperate climates, there were also cases in which plasticity was increased in temperate flies, as well as no changes in expression plasticity between flies from different climates.
Comparing Ultraconserved Elements and Exons for Phylogenomic Analyses of Middle American Cichlids: When Data Agree to Disagree
Authors: Alda Fernando , Ludt William B , Elías Diego J , McMahan Caleb D , Chakrabarty Prosanta
Published: July 2021

Choosing among types of genomic markers to be used in a phylogenomic study can have a major influence on the cost, design, and results of a study. Yet few attempts have been made to compare categories of next-generation sequence markers limiting our ability to compare the suitability of these different genomic fragment types. Here, we explore properties of different genomic markers to find if they vary in the accuracy of component phylogenetic trees and to clarify the causes of conflict obtained from different data sets or inference methods. As a test case, we explore the causes of discordance between phylogenetic hypotheses obtained using a novel data set of ultraconserved elements (UCEs) and a recently published exon data set of the cichlid tribe Heroini. Resolving relationships among heroine cichlids has historically been difficult, and the processes of colonization and diversification in Middle America and the Greater Antilles are not yet well understood. Despite differences in informativeness and levels of gene tree discordance between UCEs and exons, the resulting phylogenomic hypotheses generally agree on most relationships. The independent data sets disagreed in areas with low phylogenetic signal that were overwhelmed by incomplete lineage sorting and nonphylogenetic signals. For UCEs, high levels of incomplete lineage sorting were found to be the major cause of gene tree discordance, whereas, for exons, nonphylogenetic signal is most likely caused by a reduced number of highly informative loci. This paucity of informative loci in exons might be due to heterogeneous substitution rates that are problematic to model (i.e., computationally restrictive) resulting in systematic errors that UCEs (being less informative individually but more uniform) are less prone to. These results generally demonstrate the robustness of phylogenomic methods to accommodate genomic markers with different biological and phylogenetic properties. However, we identify common and unique pitfalls of different categories of genomic fragments when inferring enigmatic phylogenetic relationships.
Genetic architecture modulates diet-induced hepatic mRNA and miRNA expression profiles in Diversity Outbred mice
Authors: Que Excel , James Kristen L , Coffey Alisha R , Smallwood Tangi L , Albright Jody , Huda M Nazmul , Pomp Daniel , Sethupathy Praveen , Bennett Brian J
Published: July 2021

Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression. Here, we performed global hepatic eQTL and microRNA expression quantitative trait loci (mirQTL) analysis in a population of Diversity Outbred mice fed two different diets. We identified several key features of eQTL and mirQTL, namely differences in the mode of genetic regulation (cis or trans) between mRNA and miRNA. Approximately 50% of mirQTL are regulated by a trans-acting factor, compared to ∼25% of eQTL. We note differences in the heritability of mRNA and miRNA expression and variance explained by each eQTL or mirQTL. In general, cis-acting variants affecting mRNA or miRNA expression explain more phenotypic variance than trans-acting variants. Finally, we investigated the effect of diet on the genetic architecture of eQTL and mirQTL, highlighting the critical effects of environment on both eQTL and mirQTL. Overall, these data underscore the complex genetic regulation of two well-characterized RNA classes (mRNA and miRNA) that have critical roles in the regulation of clinical traits and disease susceptibility
Designing drug shops for young women in Tanzania: applying human-centred design to facilitate access to HIV self-testing and contraception
Authors: Hunter Lauren A , McCoy Sandra I , Rao Aarthi , Mnyippembe Agatha , Hassan Kassim , Njau Prosper , Mfaume Rashid , Liu Jenny X
Published: July 2021

Adolescent and young adult women in sub-Saharan Africa experience barriers to sexual and reproductive health (SRH) services that elevate their risk of human immunodeficiency virus (HIV) acquisition and unintended pregnancy. Community drug shops may be effective distribution points to connect young women with SRH products. Thus, we used human-centred design (HCD) to create drug shops where young women could access HIV self-testing and contraception in Shinyanga, Tanzania. Enhancing the HCD process with behavioural science, we collected diverse data (i.e. 18 in-depth interviews, 9 ‘shadowing’ interviews, 6 shop observations, 6 focus groups) to understand the latent needs and motivations of young women and drug shopkeepers, brainstormed creative solutions and iteratively refined and tested solutions for acceptability, feasibility and cultural fit. We found a widespread moral imperative to control young women’s behaviour via misinformation about SRH, community gossip and financial control. Young women often engaged in mundane shopping at the behest of others. At drug shops, few SRH products were deemed appropriate for unmarried women, and many reactively sought SRH products only after engaging in higher risk behaviours. In response to these insights, we designed the ‘Malkia Klabu’ (‘Queen Club’) loyalty programme through which young women could earn mystery prizes by shopping at drug shops and discreetly request free SRH products, including HIV self-test kits, by pointing at symbols on loyalty cards. Our HCD approach increases the likelihood that the intervention will address the specific needs and preferences of both drug shopkeepers and young women. We will evaluate its effectiveness in a randomized trial.
Organizational structure and human agency within the South African health system: a qualitative case study of health promotion
Authors: Rwafa-Ponela Teurai , Goudge Jane , Christofides Nicola
Published: July 2021

Despite international recognition of health promotion (HP) as a cost-effective way to improve population health, it is not highly regarded nor is it sufficiently institutionalized in many health systems. This diminishes its ability to deliver on its public health promises. This paper examined the role of organizational structure and human agency within the South African health system (drawing on Giddens’s structuration theory) in determining the extent of, and barriers to, the institutionalization of HP. We conducted a qualitative case study using a combination of in-depth interviews (n = 37), key informant interviews (n = 8) and one-day workshops (n = 5) with Department of Health (DoH) staff (HP and non-HP personnel) from national, provincial and district levels as well as external HP stakeholders. Within the South African health system, there are dedicated HP staffs, with no specified professional competencies or a coherent hierarchy of job titles. Allocated HP resources were frequently shifted to other programmes. This resulted in a disconnect between national and provincial levels, which impeded communication and opportunity to develop a shared vision and coherent programme. We found some examples of successful HP organization and implementation practices, such as the tobacco control legislation. Overall, HP staff had limited agency and were often unable to articulate the vision for HP. Uncertainty about the role of HP has led to powerlessness, and feelings of resentment have generated demotivation and moral distress. HP voices were seldom heard and were repressed by dominant curative-focused structures. If leaders of HP continue to be embedded in such an institution, there is little chance of driving an effective HP agenda. Therefore, there is a need to engage policy-makers to integrate HP into the health system fabric. Establishment of an independent HP foundation could be one mechanism to drive multi-sectoral collaboration, contribute to evidence-based HP research and further develop health in all policies through advocacy.
Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders
Authors: van Duijvenboden Stefan , Ramírez Julia , Young William J , Orini Michele , Mifsud Borbala , Tinker Andrew , Lambiase Pier D , Munroe Patricia B
Published: July 2021

The resting QT interval, an electrocardiographic (ECG) measure of ventricular myocardial repolarization, is a heritable risk marker of cardiovascular mortality, but the mechanisms remain incompletely understood. Previously reported candidate genes have provided insights into the regulatory mechanisms of the QT interval. However, there are still important knowledge gaps. We aimed to gain new insights by (i) providing new candidate genes, (ii) identifying pleiotropic associations with other cardiovascular traits, and (iii) scanning for sexually dimorphic genetic effects. We conducted a genome-wide association analysis for resting QT interval with ~9.8 million variants in 52 107 individuals of European ancestry without known cardiovascular disease from the UK Biobank. We identified 40 loci, 13 of which were novel, including 2 potential sex-specific loci, explaining ~11% of the trait variance. Candidate genes at novel loci were involved in myocardial structure and arrhythmogenic cardiomyopathy. Investigation of pleiotropic effects of QT interval variants using phenome-wide association analyses in 302 000 unrelated individuals from the UK Biobank and pairwise genome-wide comparisons with other ECG and cardiac imaging traits revealed genetic overlap with atrial electrical pathology. These findings provide novel insights into how abnormal myocardial repolarization and increased cardiovascular mortality may be linked.
The International Human Genome Project
Authors: Birney Ewan
Published: July 2021

The human genome project was conceived and executed as an international project, due to both pragmatic and principled reasons. This internationality has served the project well, with the resulting human genome being freely available for all researchers in all countries. Over time the reference human genome will likely have to evolve to a graph genome, and tap into more diverse sequences worldwide. A similar international mindset underpins data analysis for the interpretation of the human genome from basic to clinical research.
Box lesion or bi-atrial lesion set for atrial fibrillation during thoracoscopic epicardial ablation
Authors: Zheng Zhe , Li Haojie , Liu Sheng , Gao Ge , Yu Chunyu , Lin Hengqiang , Meng Ying
Published: July 2021

OBJECTIVES

Thoracoscopic epicardial ablation with a limited lesion set led to suboptimal results for advanced paroxysmal atrial fibrillation (AF) or persistent AF. Whether additional right atrial lesions improve the result is unclear.

METHODS

We conducted a retrospective study involving 80 consecutive patients with paroxysmal or persistent AF, left atrial (LA) dilation (LA diameter >40 mm) and failed prior interventional ablation (40 patients, 50%) who underwent thoracoscopic epicardial ablation with box lesions (36 patients) or bi-atrial (BA) lesion (44 patients) in our institution. Freedom from atrial tachyarrhythmias after the procedures was compared between the box lesion group and BA lesion group.

RESULTS

Baseline differences included more patients with persistent AF (86.4% vs 47.2%) and larger left atrium [48.00 (44.00–50.75) vs 42.00 (41.25–44.00) mm] in the BA lesion group. There was no difference in procedural complications between the 2 groups. After a mean follow-up of 32 months, the freedom from atrial tachyarrhythmias off antiarrhythmic drugs at 6, 12 and 24 months was 77.2%, 77.2% and 77.2% in the BA lesion group and 69.4%, 50.0% and 40.6% in the box lesion group, respectively (P = 0.006). After adjustment for sex, age, body mass index, LA diameter, AF type, history of AF, and previous interventional ablation, BA lesion was an independent predictor of lower atrial tachyarrhythmia recurrence (hazard ratio 0.447, 95% confidential interval 0.208–0.963; P = 0.040).

CONCLUSIONS

Compared with the box lesion set, thoracoscopic epicardial ablation with BA lesion sets might provide better freedom from atrial tachyarrhythmias for paroxysmal or persistent AF with LA dilation. Randomized control trials are warranted to confirm the benefit of BA lesion sets in these patients.
Appropriateness of imaging decisions for low back pain presenting to the emergency department: a retrospective chart review study
Authors: Traeger Adrian C , Machado Gustavo C , Bath Sally , Tran Martin , Roper Lucinda , Oliveira Crystian , Peek Aimie , Coombs Danielle , Hall Amanda , Tcharkhedian Elise , Maher Chris G
Published: July 2021

Background

Imaging for low back pain is widely regarded as a target for efforts to reduce low-value care.

Objective

We aimed to estimate the prevalence of the overuse and underuse of lumbar imaging in patients presenting with low back pain to the emergency department (ED).

Methods

This was a retrospective chart review study of five public hospital EDs in Sydney, Australia, in 2019–20. We reviewed the clinical charts of consecutive adult patients who presented with a complaint of low back pain and extracted clinical features relevant to a decision to request lumbar imaging. We estimated the proportion of encounters where a decision to request lumbar imaging was inappropriate (overuse) or where a clinician did not request an appropriate and informative lumbar imaging test when indicated (underuse).

Results

Six hundred and forty-nine patients presented with a complaint of low back pain, of which 158 (24.3%) were referred for imaging. Seventy-nine (12.2%) had a combination of features suggesting that lumbar imaging was indicated according to clinical guidelines. The prevalence of overuse and underuse of lumbar imaging was 8.8% (57 of 649 cases, 95% CI 6.8–11.2%) and 4.3% (28 of 649 cases, 95% CI 3.0–6.1%), respectively. Thirteen cases were classified as underuse because the patients were referred for uninformative imaging modalities (e.g. referred for radiography for suspected cauda equina syndrome).

Conclusion

In this study of emergency care, there was evidence of not only overuse of lumbar imaging but also underuse through failure to request lumbar imaging when indicated or referral for an uninformative imaging modality. These three issues seem more important targets for quality improvement than solely focusing on overuse.