bluuebunny/crossref_metadata_2025 huggingface dataset:
Categorical representation learning: morphism is all you need
Authors: Sheshmani Artan , You Yi-Zhuang
Published: October 2021

We provide a construction for categorical representation learning and introduce the foundations of ‘categorifier’. The central theme in representation learning is the idea of everything to vector. Every object in a dataset

S

can be represented as a vector in

R

n

by an encoding map

E
:

O

b
j
(

S

)
→

R

n

. More importantly, every morphism can be represented as a matrix

E
:

H

o
m
(

S

)
→

R

n

n

. The encoding map E is generally modeled by a deep neural network. The goal of representation learning is to design appropriate tasks on the dataset to train the encoding map (assuming that an encoding is optimal if it universally optimizes the performance on various tasks). However, the latter is still a set-theoretic approach. The goal of the current article is to promote the representation learning to a new level via a category-theoretic approach. As a proof of concept, we provide an example of a text translator equipped with our technology, showing that our categorical learning model outperforms the current deep learning models by 17 times. The content of the current article is part of a US provisional patent application filed by QGNai, Inc.
A case report of multi-system inflammatory syndrome in adults (MIS-A) associated with heart failure
Authors: Mittal Nitish , Abohelwa Mostafa , Brogan Joshua , Nichols Jacob
Published: October 2021

Background

Multi-system inflammatory syndrome in children (MIS-C) is a systemic inflammatory condition where various body organs, such as the heart, kidney, gastrointestinal organs, become inflamed. Several cases have been reported in children linking MIS-C with novel corona virus disease-2019 (COVID-19); however, few cases have been reported in adults [multi-system inflammatory syndrome in adults (MIS-A)].

Case summary

A case of a 20-year-old male patient with a history of COVID-19 infection 2 months before presentation who presented with fever and acute right lower quadrant pain. Workup revealed right-sided mesenteric lymphadenopathy and mild colitis that was non-responsive to antibiotics. The patient was found to have significantly elevated inflammatory markers. He also developed myocarditis resulting in acute systolic heart failure with reduced ejection fraction. The diagnosis of MIS-A was made by exclusion. The patient showed improvement with intravenous immunoglobulin and pulse steroids. Based on the available literature, MIS-C was defined till the age of 21; however, we think it is a misnomer for adults more than 18. Hence, we prefer to use MIS-A for our patient.

Conclusion

It is essential to diagnose and treat patients with the multi-system inflammatory syndrome at an early stage; the management of these patients, especially with heart disease, should include immune-modulatory therapy as well as guideline-directed therapy.
Unconventional treatment of a giant coronary aneurysm presenting as ST-elevation myocardial infarction: a case report
Authors: Barioli Alberto , Pellizzari Nicola , Favero Luca , Cernetti Carlo
Published: October 2021

Background

The optimal treatment of aneurysmal or ectatic culprit vessels in the setting of acute myocardial infarction is still matter of debate, as revascularization with either percutaneous intervention or surgery is associated with low procedural success and poor outcomes.

Case summary

We report the case of a 55-year-old male patient, admitted for inferior ST-elevation myocardial infarction, who underwent successful percutaneous implantation of a micro-mesh self-expanding nitinol carotid stent in a right coronary aneurysm with intravascular ultrasonography measured diameter of 9 mm and massive thrombus apposition.

Discussion

The technical characteristics of the micro-mesh self-expanding nitinol carotid stent allow for adequate plaque coverage and good apposition even in large vessels, making this device particularly suitable for the treatment of coronary lesions with high thrombus burden, when severe coronary ectasia or aneurysms are present.
Motivational interviewing as a new approach to improve outcome through self-care behavioural changes in advanced heart failure patient: a case report
Authors: Sakane Kazushi , Kanzaki Yumiko , Ito Takahide , Hoshiga Masaaki
Published: October 2021

Background

A lack of adherence and inadequate self-care behaviours are common reasons for recurrent hospitalizations among patients with heart failure (HF). Although patients recognize the importance of HF self-care, it is sometimes difficult to correct their behavioural patterns. Motivational interviewing is a communication technique to resolve ambivalence towards changing behaviour, and it has been widely used to promote behavioural changes and improve outcomes in various chronic diseases. We described a case of advanced HF with reduced ejection fraction in which motivational interviewing lead to stabilize the patient’s condition.

Case summary 

A 33-year-old man was diagnosed with dilated cardiomyopathy who experienced repeated episodes of HF requiring hospitalization despite optimal guideline-based HF treatment. Transthoracic echocardiography disclosed a severely reduced left ventricular (LV) contraction (LV ejection fraction 18%) and cardiopulmonary exercise testing disclosed markedly reduced functional capacity and increased ventilatory response (peak VO2 of 10.7 mL/min/kg, predicted peak VO2 of 34.7% and VE/VCO2 slope of 35.2). In this case, poor adherence to self-care such as excessive fluid intake and excessive daily activities after hospital discharge was the main cause of recurrent hospitalization for HF. Despite repeated patient education to correct his diet and lifestyle, he could not change his lifestyle behaviour. However, motivational interviewing dramatically helped stabilize the patient’s condition and prevent HF re-hospitalization.

Discussion 

In general, patients with advanced HF and reduced ejection fraction despite optimal medical therapy should be evaluated to assess their eligibility of cardiac transplantation or palliative care. Motivational interviewing might represent a new therapeutic approach for stabilizing and preventing HF through self-care behavioural changes, even in patients with advanced HF and severely reduced ejection fraction.
Population genomics of Drosophila suzukii reveal longitudinal population structure and signals of migrations in and out of the continental United States
Authors: Lewald Kyle M , Abrieux Antoine , Wilson Derek A , Lee Yoosook , Conner William R , Andreazza Felipe , Beers Elizabeth H , Burrack Hannah J , Daane Kent M , Diepenbrock Lauren , Drummond Francis A , Fanning Philip D , Gaffney Michael T , Hesler Stephen P , Ioriatti Claudio , Isaacs Rufus , Little Brian A , Loeb Gregory M , Miller Betsey , Nava Dori E , Rendon Dalila , Sial Ashfaq A , Bezerra da Silva Cherre S , Stockton Dara G , Van Timmeren Steven , Wallingford Anna , Walton Vaughn M , Wang Xingeng , Zhao Bo , Zalom Frank G , Chiu Joanna C
Published: October 2021

Drosophila suzukii, or spotted-wing drosophila, is now an established pest in many parts of the world, causing significant damage to numerous fruit crop industries. Native to East Asia, D. suzukii infestations started in the United States a decade ago, occupying a wide range of climates. To better understand invasion ecology of this pest, knowledge of past migration events, population structure, and genetic diversity is needed. In this study, we sequenced whole genomes of 237 individual flies collected across the continental United States, as well as several sites in Europe, Brazil, and Asia, to identify and analyze hundreds of thousands of genetic markers. We observed strong population structure between Western and Eastern US populations, but no evidence of any population structure between different latitudes within the continental United States, suggesting that there are no broad-scale adaptations occurring in response to differences in winter climates. We detect admixture from Hawaii to the Western United States and from the Eastern United States to Europe, in agreement with previously identified introduction routes inferred from microsatellite analysis. We also detect potential signals of admixture from the Western United States back to Asia, which could have important implications for shipping and quarantine policies for exported agriculture. We anticipate this large genomic dataset will spur future research into the genomic adaptations underlying D. suzukii pest activity and development of novel control methods for this agricultural pest.
Functional requirements of protein kinases and phosphatases in the development of the Drosophila melanogaster wing
Authors: Ostalé Cristina M , Esteban Nuria , López-Varea Ana , de Celis Jose F
Published: October 2021

Protein kinases and phosphatases constitute a large family of conserved enzymes that control a variety of biological processes by regulating the phosphorylation state of target proteins. They play fundamental regulatory roles during cell cycle progression and signaling, among other key aspects of multicellular development. The complement of protein kinases and phosphatases includes approximately 326 members in Drosophila, and they have been the subject of several functional screens searching for novel components of signaling pathways and regulators of cell division and survival. These approaches have been carried out mostly in cell cultures using RNA interference to evaluate the contribution of each protein in different functional assays and have contributed significantly to assign specific roles to the corresponding genes. In this work, we describe the results of an evaluation of the Drosophila complement of kinases and phosphatases using the wing as a system to identify their functional requirements in vivo. We also describe the results of several modifying screens aiming to identify among the set of protein kinases and phosphatases additional components or regulators of the activities of the epidermal growth factor and insulin receptors signaling pathways.
Genome-wide phenotypic RNAi screen in theDrosophilawing: phenotypic description of functional classes
Authors: López-Varea Ana , Vega-Cuesta Patricia , Ruiz-Gómez Ana , Ostalé Cristina M , Molnar Cristina , Hevia Covadonga F , Martín Mercedes , Organista Maria F , de Celis Jesus , Culí Joaquín , Esteban Nuria , de Celis Jose F
Published: October 2021

The Drosophila genome contains approximately 14,000 protein-coding genes encoding all the necessary information to sustain cellular physiology, tissue organization, organism development, and behavior. In this manuscript, we describe in some detail the phenotypes in the adult fly wing generated after knockdown of approximately 80% of Drosophila genes. We combined this phenotypic description with a comprehensive molecular classification of the Drosophila proteins into classes that summarize the main expected or known biochemical/functional aspect of each protein. This information, combined with mRNA expression levels and in situ expression patterns, provides a simplified atlas of the Drosophila genome, from housekeeping proteins to the components of the signaling pathways directing wing development, that might help to further understand the contribution of each gene group to wing formation.
Genome-wide phenotypic RNAi screen in theDrosophilawing: global parameters
Authors: López-Varea Ana , Ostalé Cristina M , Vega-Cuesta Patricia , Ruiz-Gómez Ana , Organista María F , Martín Mercedes , Hevia Covadonga F , Molnar Cristina , de Celis Jesús , Culi Joaquim , Esteban Nuria , de Celis Jose F
Published: October 2021

We have screened a collection of UAS-RNAi lines targeting 10,920 Drosophila protein-coding genes for phenotypes in the adult wing. We identified 3653 genes (33%) whose knockdown causes either larval/pupal lethality or a mutant phenotype affecting the formation of a normal wing. The most frequent phenotypes consist of changes in wing size, vein differentiation, and patterning, defects in the wing margin and in the apposition of the dorsal and ventral wing surfaces. We also defined 16 functional categories encompassing the most relevant aspect of each protein function and assigned each Drosophila gene to one of these functional groups. This allowed us to identify which mutant phenotypes are enriched within each functional group. Finally, we used previously published gene expression datasets to determine which genes are or are not expressed in the wing disc. Integrating expression, phenotypic and molecular information offers considerable precision to identify the relevant genes affecting wing formation and the biological processes regulated by them.
Reconstruction of human genome evolution in yeast: an educational primer for use with “systematic humanization of the yeast cytoskeleton discerns functionally replaceable from divergent human genes”
Authors: Brzáčová Zuzana , Peťková Mária , Veljačiková Katarína , Zajičková Terézia , Tomáška Ľubomír
Published: October 2021

The evolution of eukaryotic organisms starting with the last eukaryotic common ancestor was accompanied by lineage-specific expansion of gene families. A paper by Garge et al. provides an excellent opportunity to have students explore how expansion of gene families via gene duplication results in protein specialization, in this case in the context of eukaryotic cytoskeletal organization . The authors tested hypotheses about conserved protein function by systematic “humanization” of the yeast cytoskeletal components while employing a wide variety of methodological approaches. We outline several exercises to promote students’ ability to explore the genomic databases, perform bioinformatic analyses, design experiments for functional analysis of human genes in yeast and critically interpret results to address both specific and general questions.
Humanoids for teaching and training coronary artery bypass surgery to the next generation of cardiac surgeons
Authors: Tozzi Piergiorgio , Ferrari Enrico , Reuthebuch Oliver , Matt Peter , Huber Christoph , Eckstein Friedrich , Kirsch Matthias , Mestres Carlos A
Published: October 2021

OBJECTIVES

Technical skills are an essential component of cardiac surgery, and the operating room is becoming an even more challenging environment for trainees who want to acquire such skills. Simulation, which partially overcomes this limitation, represents a valid adjunct to surgical education. We describe an original simulator and provide results in terms of trainees’ evaluations and ratings.

METHODS

We used a humanoid that is a silicone replica of the chest of an adult human that provides a complete anatomical platform for hands-on skin-to-skin practice of surgical techniques in arrested heart coronary artery bypass graft (CABG) surgery cases. Learners were residents in cardiac surgery. The teaching sessions included 2 full three-vessel CABG procedures using both mammary arteries and a hydrogel vein. Five board-certified cardiovascular surgeons scored the surgical activity of all trainees. The trainees were asked to complete an exit questionnaire to evaluate their course.

RESULTS

Overall, 16 residents participated in the simulation, including 5 women and 11 men, with a mean age of 30 ± 4 years, all of whom had at least 2 years of cardiac surgery training. All participants completed the 2 CABG operations. Three mammary arteries (4.6%) were seriously damaged during harvesting. In 1 case (3.1%), an aortic tear occurred during aortic cannulation. Each trainee performed overall 6 distal and 2 proximal coronary anastomoses. All participants agreed that the ‘humanoid reproduces real-life situations, the feeling is realistic, and they are now more confident in performing coronary anastomosis’.

CONCLUSIONS

Trainees involved in this simulation curriculum acquired and refined technical skills that could be applied directly to human patients. In addition, we were able to foster a higher level of teamwork within the operating room team.
Recommendations for Screening and Diagnosis of Chagas Disease in the United States
Authors: Forsyth Colin J , Manne-Goehler Jennifer , Bern Caryn , Whitman Jeffrey , Hochberg Natasha S , Edwards Morven , Marcus Rachel , Beatty Norman L , Castro-Sesquen Yagahira E , Coyle Christina , Stigler Granados Paula , Hamer Davidson , Maguire James H , Gilman Robert H , Meymandi Sheba
Published: October 2021

Background

Chagas disease affects an estimated 326 000–347 000 people in the United States and is severely underdiagnosed. Lack of awareness and clarity regarding screening and diagnosis is a key barrier. This article provides straightforward recommendations, with the goal of simplifying identification and testing of people at risk for US healthcare providers.

Methods

A multidisciplinary working group of clinicians and researchers with expertise in Chagas disease agreed on 6 main questions, and developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, after reviewing the relevant literature on Chagas disease in the United States.

Results

Individuals who were born or resided for prolonged time periods in endemic countries of Mexico and Central and South America should be tested for Trypanosoma cruzi infection, and family members of people who test positive should be screened. Women of childbearing age with risk factors and infants born to seropositive mothers deserve special consideration due to the risk of vertical transmission. Diagnostic testing for chronic T. cruzi infection should be conducted using 2 distinct assays.

Conclusions

Increasing provider-directed screening for T. cruzi infection is key to addressing this neglected public health challenge in the United States.
Mycotoxin deactivator improves performance, antioxidant status, and reduces oxidative stress in nursery pigs fed diets containing mycotoxins
Authors: Santos Erika Vivian , Fontes Dalton Oliveira , Benfato Mara da Silveira , Hackenhaar Fernanda Schäfer , Salomon Tiago , Jacob David Vani , Prévéraud Damien , Araujo Wagner Azis Garcia , da Glória Eduardo Maria , Domingos Rodrigo Lima , Lopes Idael Mateus Goes , Guedes Lis Lorena Melúcio , Lima Valesca Ribeiro , Cardoso Larissa Alves , Silva Bruno Alexander Nunes
Published: October 2021

Ingestion of mycotoxins can result in many problems, including decreased growth rates and immune suppression. The present study aimed to evaluate the impact of the supplementation of a mycotoxin deactivator composed by adsorbent clay minerals; inactivated fermentation extracts of Saccharomyces cerevisiae; and blend of antioxidants, organic acids, and botanicals in diets containing added mycotoxins for nursery pigs on their performance and antioxidant status. Ninety pigs weaned with 24 d of age (7.12 ± 0.68 kg of BW) were used. Pigs were housed in pens of three animals each according to body weight, litter origin, and sex. The dietary treatments consisted of feeding the pigs with a standard control diet as negative control (NC; mycotoxin levels at accepted regulatory Brazilian Ministry of Agriculture standards; deoxynivalenol (DON): <100 μg/kg; zearalenone (ZEA): <20 μg/kg; fumonisins (FB): <1 mg/kg); the standard diet added with mycotoxins to reach a low contamination level is considered as positive low (PCL−; DON: 900 μg/kg; ZEA: 100 μg/kg; FB: 5,000 μg/kg) without deactivator; a positive low added the deactivator at an inclusion rate of 1 kg/ton (PCL+); the standard diet added with mycotoxins to reach a high contamination level is considered as positive high (PCH−; DON: 4,500 μg/kg; ZEA: 500 μg/kg; FB: 18,000 μg/kg) without the deactivator; and a positive high added the deactivator at an inclusion rate of 5 kg/ton (PCH+). Pigs were individually weighed at the beginning and at the end of each phase and feed intake recorded based on daily pen intake during the experiment. On days 7, 19, 34, and 43 post-weaning, blood samples were drawn for antioxidant analyses. Antioxidant enzymes (glutathione peroxidase [GPx] and total superoxide dismutase [TSOD]), vitamins [Vit A, E, and C], and malondialdehyde [MDA]) were evaluated in erythrocyte and plasma samples. Pigs challenged with mycotoxins presented lower performance traits, decrease in the efficiency of central antioxidant systems (↓GPx, ↓TSOD, ↓Vit A, ↓Vit E, and ↓Vit C), and a higher oxidative damage to lipids (↑MDA) when compared with the control and deactivator-associated treatments. Our findings showed that the use of a mycotoxin deactivator can mitigate the negative impacts on performance and oxidative stress when animals are subjected to diets contaminated by different levels of mycotoxins.
Herbage mass and allowance and animal genotype affect daily herbage intake, productivity, and efficiency of beef cows grazing native subtropical grassland
Authors: Do Carmo Martin , Genro Teresa C M , Cibils Andrés F , Soca Pablo M
Published: October 2021

The beef sector in Campos grasslands must increase animal productivity without external inputs, while reducing environmental impact. The objective of this study was to estimate herbage intake (g/metabolic body weight [MBW]/d) of straightbred (Hereford/Angus) and crossbred (F1 of Hereford × Angus) beef cows grazing subtropical native grassland with High and Low herbage allowance (HA, 5 vs. 3 kg DM/kg bodyweight [BW]) during gestation and lactation and its relationship with biological efficiency of cow-calf productivity. Herbage intake (estimated via n-alkanes C32:C33 ratio) was measured during early (Ge1, −163 d prior calving) and mid to late [Gm1 (−83) and Gm2 (−90 d prior calving)] gestation and lactation (L0, L1, and L2, 60, 47, and 31d following calving) periods in 24 to 36 cows, selected to create 8 groups (4 per block) of HA × cow genotype treatment. Cows grazed native grassland year-round, under High and Low HA (except in winter). We analyzed the effect of cow genotype (straightbred vs. crossbred cows) and HA (High vs. Low) on herbage mass and height, daily herbage intake rate (DMI), cow body condition score (BCS), calf average daily gain (ADG) and BW at weaning (BWW) and g of calf weaned/kg DMI. High allowance improved DMI during lactation periods (High 115.6 vs. Low 94.1 ± 5.3; P < 0.05 g/MBW/d). Crossbred cows decreased DMI during gestation (Crossbred 81 vs. Straightbred 94 ± 4.3; P = 0.05 g/MBW/d) compared with straightbred cows. Crossbred and High HA improved biological efficiency, 40.0 vs. 26.2 and 36.0 vs. 29.7 g of calf/kg DMI, respectively. High allowance increased herbage mass and sites with greater canopy height that allow greater DMI, positively associated with cow BCS at weaning, calf ADG, BWW, and g of calf/kg DMI. Crossbred cows reduced DMI during gestation showing no greater annual DMI. Animal productivity and biological efficiency can be improved using High HA and crossbred cows, which should decrease the environmental impact of cow-calf systems.
Black Insecurity at the End of the World
Authors: Mann Justin L
Published: October 2021

“Black Insecurity at the End of the World” examines the sensibility I term black insecurity by reading Colson Whitehead’s 2010 novel Zone One against a backdrop of bioinsecurity and police murder of black people. The 2014 Ebola outbreak in West Africa and uprisings in Ferguson, Missouri, from the same year, when situated in dialogue with Whitehead’s text, show that black insecurity reframes the spatio-temporal notion of survival by unmasking security structures as dead and dying. Engaged from the standpoint of ongoing racial justice protests and stay-at-home conditions of the COVID-19 pandemic, “Black Insecurity at the End of the World” argues that black speculative fictions uniquely expose the false premises of securitization and show that black love is an essential process for unmaking the forces of anti-Blackness.
Trophic ecology of the Hubb's octopus Octopus hubbsorum (Cephalopoda: Octopodidae) in the central Mexican Pacific
Authors: Serrano-Tadeo Martín , Flores-Ortega Juan Ramón , Godínez-Domínguez Enrique , Granados-Amores Jasmín , Zavala-Leal Oscar Iram , Granados-Amores Andrés
Published: October 2021

The diet of the Hubb's octopus Octopus hubbsorum along the coast of Acapulco, Guerrero, Mexico, was determined by analysing the stomach contents of 413 individuals collected monthly between February 2017 and March 2018. Most stomachs (74.3%) presented contents, while 25.7% were empty. Sixty prey items were identified and grouped into 16 categories. The most frequent prey items were Petrolisthes sanfelipensis, Clastotoechus diffractus, Petrolisthes hians and Alpheus spp. Smith's index indicated that O. hubbsorum follows a generalist diet for each hydroclimatic season, sex and size class (1: juvenile; 2: young adult; 3: mature adult). Cannibalism was frequent among males, less so among females. Pianka's index revealed a higher overlap among the three size classes of both sexes during the dry season, while during the rainy season the overlap was reduced for size classes 2 and 3 in both sexes. The average isotopic values overall were δ13C −14.96‰ (±0.08) and δ15N 13.02‰ (±0.09). A significant difference (P = 0.005) was observed in δ13C among hydroclimatic seasons (rainy and dry) and size classes, while for δ15N a significant difference (P = 0.013) was observed between seasons. Stomach content analysis gave values of the trophic position of O. hubbsorum ranging from 3.57 to 3.72, whereas the values obtained using stable isotope analysis, using δ15N, ranged from 3.52 to 3.86. Variation was observed in isotopic niche size and Layman's metrics among hydroclimatic seasons. A higher isotopic niche overlap was observed between size classes 2 and 3 during the dry season. The rocky shore ecosystem has been heavily exploited by artisanal fisheries (fish and invertebrates). A more integrated, ecosystem-based management of these fisheries requires an understanding of their trophic structure.
Marizomib alone or in combination with bevacizumab in patients with recurrent glioblastoma: Phase I/II clinical trial data
Authors: Bota Daniela A , Mason Warren , Kesari Santosh , Magge Rajiv , Winograd Benjamin , Elias Ileana , Reich Steven D , Levin Nancy , Trikha Mohit , Desjardins Annick
Published: October 2021

Background

This phase I/II trial in patients with recurrent glioblastoma (GBM) evaluates the safety and preliminary efficacy of marizomib, an irreversible pan-proteasome inhibitor that crosses the blood–brain barrier.

Methods

Part A assessed the safety and efficacy of marizomib monotherapy. In Part B, escalating doses of marizomib (0.5–0.8 mg/m2) in combination with bevacizumab were evaluated. Part C explored intra-patient dose escalation of marizomib (0.8–1.0 mg/m2) for the combination.

Results

In Part A, 30 patients received marizomib monotherapy. The most common AEs were fatigue (66.7%), headache (46.7%), hallucination (43.3%), and insomnia (43.3%). One patient (3.3%) achieved a partial response. In Part B, the recommended phase II dose of marizomib was 0.8 mg/m2 when combined with bevacizumab 10 mg/kg. In Part C, dose escalation to 1.0 mg/m2 was not tolerated. Pooled analysis of 67 patients treated with marizomib ≤0.8 mg/m2 and bevacizumab showed a nonoverlapping safety profile consistent with the known safety profile of each agent: the most common grade ≥3 AEs were hypertension (16.4%), confusion (13.4%), headache (10.4%), and fatigue (10.4%). The overall response rate was 34.3%, including 2 patients with complete response. Six-month progression-free survival was 29.8%; median overall survival was 9.1 months.

Conclusions

The safety profile of marizomib as monotherapy and in combination with bevacizumab was consistent with previous observations that marizomib crosses the blood–brain barrier. Preliminary efficacy did not demonstrate a meaningful benefit of the addition of marizomib to bevacizumab for the treatment of recurrent GBM.
Mefenoxam Sensitivity in US-8 and US-23 Phytophthora infestans from Wisconsin
Authors: Larson Eric R. , Migliano Lukas E. , Chen Yu , Gevens Amanda J.
Published: October 2021

The contemporary dominant clonal lineage of heterothallic Phytophthora infestans in Wisconsin, US-23, is classified as sensitive to the systemic fungicide mefenoxam and is of the A1 mating type. With the sporadic appearance of clonal lineage US-8, classified as resistant to mefenoxam and of the A2 mating type, there is a need for ongoing monitoring and characterization. Isolates of P. infestans collected from Wisconsin during the 2017 and 2018 growing seasons were tested for sensitivity to mefenoxam with discriminatory dose of 100 ppm. In 2017, both US-23 and US-8 were isolated. On average, isolates of US-23 were significantly more sensitive to mefenoxam than were US-8 isolates (P = 8e-04). There were significant differences in the sensitivity levels among the US-8 isolates (P = 2.02e-06), with a single isolate testing sensitive at 100 ppm of mefenoxam based on the one-way ANOVA. There were significant differences in the sensitivity levels among US-23 isolates (P = 3.75e-09), with two isolates showing resistance. In 2018 only US-23 was found, and isolates were tested for mefenoxam response at 0, 0.1, 1, 10, and 100 ppm. At 0.1 ppm, isolates showed significantly different levels of sensitivity (P = 2.1e-09), and a single isolate showed complete resistance. Isolates from both clonal lineages and years that exhibited moderate levels of resistance had greater variability among replicates. The phenotype of this multigenic trait comes through in the variability seen in isolates that are showing more resistance. Continued screening of P. infestans for mefenoxam sensitivity will help track the development and mechanism of resistance, as well as aid in development of best management approaches.
Evaluation of Fungicide Efficacy on Sunflower Rust (Puccinia helianthi) on Oilseed and Confection Sunflower
Authors: Berghuis Brandt , Friskop Andrew , Gilley Michelle , Halvorson Jessica , Hansen Bryan , Fitterer Scott , Carruth Dave , Schatz Blaine , Benson Bob , Humann Ryan , Markell Samuel
Published: October 2021

Sunflower rust, caused by Puccinia helianthi, is an economically and globally important disease of sunflower. Two types of sunflower are produced in the U.S. Northern Great Plains: the oilseed type and the confection type. Although approximately 80% of the acreage in this region is planted as the oilseed-type sunflower, fungicide efficacy and timing studies have been conducted primarily on the more rust-susceptible confection type. In total, 10 sunflower rust efficacy field experiments were conducted on oilseed type and confectionary type hybrid trials from 2016 to 2018. Eleven fungicides from three Fungicide Resistance Action Committee groups were evaluated for efficacy and protection of yield. Severity differences among fungicide treatments were identified in both confection and oilseed sunflower trials. A combined analysis of all confection field trials (five) indicated that rust severity was lower in all fungicide treatments as compared with the nontreated control. Despite rust severity levels below the recommended fungicide action threshold for confection sunflower, 7 of the 11 fungicide treatments had yield higher than the nontreated control. In oilseed trials, rust severity was lower in all fungicide treatments as compared with the nontreated control, similar to the findings of the confection type. Rust severity was too low to detect yield differences in oilseed trials. Additional work is needed to elucidate yield-loss potential on oilseed-type sunflower and refine the fungicide action threshold on confection-type sunflower.
First Report That Mucor irregularis Causes White Mold Disease on Substrates Used for Wine-Cap Mushroom (Stropharia rugosoannulata) Cultivation in China
Authors: Li Chuang , Wang Qing , Qin Jinhua , Wang Leiming , Wen Zhenghuai , Gu Aibing , Jiang Shouhua , Zhou Gang , Zhao Chen , Wang Guolian
Published: October 2021

Stropharia rugosoannulata is a popular edible mushroom. In October 2020, white mold disease was found on substrates of S. rugosoannulata in a heliogreenhouse in Huai’an city, Jiangsu province, China. The cultivation materials included rice straw (30%), wheat straw (30%), saw dust (30%), and a small amount of wheat bran (5%) and rice bran (5%). In the diseased substrates, a large amount of thick white fungal mycelia was observed with yellow ooze on the surface, which prevented the growth of the mycelia and fruiting bodies of S. rugosoannulata. Disease incidence was calculated as ∼30%. The fungus was identified morphologically and through DNA as Mucor irregularis, and pathogenicity was confirmed. In order to ensure the safe production of S. rugosoannulata, once white mold disease is found, the infected tissue should be removed. This is the first report that M. irregularis causes white mold disease on S. rugosoannulata in China.
Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing
Authors: Stevanovski Igor , Chintalaphani Sanjog R. , Gamaarachchi Hasindu , Ferguson James M. , Pineda Sandy S. , Scriba Carolin K. , Tchan Michel , Fung Victor , Ng Karl , Cortese Andrea , Houlden Henry , Dobson-Stone Carol , Fitzpatrick Lauren , Halliday Glenda , Ravenscroft Gianina , Davis Mark R. , Laing Nigel G. , Fellner Avi , Kennerson Marina , Kumar Kishore R. , Deveson Ira W.
Published: October 2021

Short-tandem repeat (STR) expansions are an important class of pathogenic genetic variants. Over forty neurological and neuromuscular diseases are caused by STR expansions, with 37 different genes implicated to date. Here we describe the use of programmable targeted long-read sequencing with Oxford Nanopore’s ReadUntil function for parallel genotyping of all known neuropathogenic STRs in a single, simple assay. Our approach enables accurate, haplotype-resolved assembly and DNA methylation profiling of expanded and non-expanded STR sites. In doing so, the assay correctly diagnoses all individuals in a cohort of patients (n = 27) with various neurogenetic diseases, including Huntington’s disease, fragile X syndrome and cerebellar ataxia (CANVAS) and others. Targeted long-read sequencing solves large and complex STR expansions that confound established molecular tests and short-read sequencing, and identifies non-canonical STR motif conformations and internal sequence interruptions. Even in our relatively small cohort, we observe a wide diversity of STR alleles of known and unknown pathogenicity, suggesting that long-read sequencing will redefine the genetic landscape of STR expansion disorders. Finally, we show how the flexible inclusion of pharmacogenomics (PGx) genes as secondary ReadUntil targets can identify clinically actionable PGx genotypes to further inform patient care, at no extra cost. Our study addresses the need for improved techniques for genetic diagnosis of STR expansion disorders and illustrates the broad utility of programmable long-read sequencing for clinical genomics.

One sentence summary

This study describes the development and validation of a programmable targeted nanopore sequencing assay for parallel genetic diagnosis of all known pathogenic short-tandem repeats (STRs) in a single, simple test.
Efficacy of COVID-19 vaccines in immunocompromised patients: A systematic review and meta-analysis
Authors: Lee Ainsley Ryan Yan Bin , Wong Shi Yin , Chai Louis Yi Ann , Lee Soo Chin , Lee Matilda , Muthiah Mark Dhinesh , Tay Sen Hee , Teo Chong Boon , Tan Benjamin Kye Jyn , Chan Yiong Huak , Sundar Raghav , Soon Yu Yang
Published: October 2021

Objective

To compare the efficacy of COVID 19 vaccines between those with immunocompromised medical conditions and those who are immunocompetent

Design

Systematic review and meta-analysis

Data sources

PubMed, EMBASE, CENTRAL, CORD-19 and WHO COVID-19 research databases were searched for eligible comparative studies published between 1 December 2020 and 3 September 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in September 2021 to identify registered yet unpublished or ongoing studies.

Study selection

Prospective observational studies which compared the efficacy of COVID-19 vaccination between those with immunocompromising medical conditions and those who were immunocompetent were included. Two reviewers independently screened for potentially eligible studies.

Data extraction

The primary outcomes of interest were cumulative incidence of seroconversion after first and second doses of COVID vaccination. Secondary outcomes included SARS-CoV-2 antibody titre level after first and second doses of COVID-19 vaccination. After duplicate data abstraction, a frequentist random effects meta-analysis was conducted. Risk of bias was assessed using the ROBINS-I tool. Certainty of evidence was assessed using the GRADE approach.

Results

After screening 3283 studies, 42 studies that met our inclusion criteria were identified. 18 immunocompromised cohorts from 17 studies reported seroconversion in immunocompromised patients compared to healthy controls after the first dose and 30 immunocompromised cohorts in 28 studies reporting data after the second dose.

Among immunocompromised groups, in incremental order, transplant recipients had the lowest pooled risk ratio of 0.06 (95%CI: 0.04 to 0.09, I^2=0%, p=0.81) (GRADE=Moderate) followed by haematological cancer patients at 0.36 (95%CI: 0.21 to 0.62, I^2 = 89%, p<0.01) (GRADE=Moderate), solid cancer patients at 0.40 (95%CI: 0.31 to 0.52, I^2 = 63%, p=0.03) (GRADE=Moderate) and IMID patients at 0.66 (95%CI: 0.48 to 0.91, I^2=81%, p<0.01) (GRADE=Moderate).

After the second dose, the lowest pooled risk ratio was again seen in transplant recipients at 0.29 (95%CI: 0.21 to 0.40, I^2=91%, p<0.01) (GRADE=Moderate), haematological cancer patients at 0.68 (95%CI: 0.57 to 0.80, I^2=68%, p=0.02) (GRADE=Low), IMID patients at 0.79 (95%CI: 0.72 to 0.86, I^2=87%, p<0.01) (GRADE=Low) and solid cancer at 0.92 (95%CI: 0.89 to 0.95, I^2=26%, p=0.25) (GRADE=Low).

Conclusion

Seroconversion rates and serological titres are significantly lower in immunocompromised patients with transplant recipients having the poorest outcomes. Additional strategies on top of the conventional 2-dose regimen will likely be warranted, such as a booster dose of the vaccine.

Systematic review registration

PROSPERO CRD42021272088
Disproportionality analysis of adverse neurological and psychiatric reactions with the ChAdOx1 (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines in the United Kingdom
Authors: Perez-Lloret Santiago , Petrovsky Nikolai , Alami Abdallah , Crispo James A.G. , Mattison Donald , Otero-Losada Matilde , Capani Francisco , Krewski Daniel
Published: October 2021

Objective

The information on neurologic or psychiatric adverse reactions to the COVID-19 vaccines is limited. Our objective was to examine the odds of neurological and psychiatric adverse reactions to BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines.

Methods

We analyzed all Adverse Vaccine Reaction reports to the United Kingdom Medicines and Healthcare products Regulatory Agency between December 9, 2020 and June 30, 2021 that mentioned the BNT162b2 or ChAdOx1 vaccines. We compared the rates of adverse neurological and psychiatric reactions with ChAdOx1 to those with BNT162b2. P-values were obtained by a Bonferroni-adjusted Z-test for proportions.

Results

As of June 30, 2021, 53.2 M doses of ChAdOx1 and 46.1 M doses of BNT162b2 had been administered. We extracted information from 300,518 distinct reports. The number of individual adverse neurologic or psychiatric reaction reports were less than 200/M doses administered, except headache which was reported in 1,550 and 395 cases/M doses of ChAdOx1 and BNT162b2, respectively. Compared to BNT162b2, cerebral hemorrhagic or thrombotic events, headaches and migraines, Guillain-Barre syndrome and paresthesias, tremor and freezing, delirium, hallucinations, nervousness, poor sleep quality, and postural dizziness were more frequently reported with ChAdOx1. Reactions more frequently reported with BNT162b2 than ChAdOx1 were Bell’s palsy, facial paralysis, dysgeusia, anxiety, and presyncope or syncope.

Conclusion

Significant differences in the neurologic and psychiatric adverse event profiles of the ChAdOx1 and BNT162b2 vaccines may exist, emphasizing the need for additional research. The beneficial and protective effects of the COVID-19 vaccines far outweigh the low potential risk of neurologic and psychiatric reactions.
Genomic profile in TGCT Mexican patients reveals a potential biomarker of sensitivity to platinum-based therapy
Authors: González-Barrios Rodrigo , Alcaraz Nicolás , Montalvo-Casimiro Michel , Cervera Alejandra , Munguia-Garza Paulina , Arriaga-Canon Cristian , Hinojosa-Ugarte Diego , Sobrevilla-Moreno Nora , Torres-Arciga Karla , Mendoza-Perez Julia , Diaz-Chavez José , Cortes Carlo Cesar , Scavuzzo Ana , Castro-Hernández Clementina , Martínez-Cedillo Jorge , Pérez-Montiel Delia , Jiménez-Ríos Miguel , Herrera Luis A.
Published: October 2021

Despite having a favorable response to platinum-based chemotherapies, ∼15% of Testicular Germ Cell Tumor (TGCT) patients are platinum resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum sensitive and 14 were platinum resistant. We incorporated analyses of mutational burden, driver mutations, SNV and CNV signatures. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplification of 2q11.1 as a novel variant with chemosensitivity biomarker potential. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. Our data sheds light into understanding platinum resistance in a poorly characterized population.
Mini-XT, a miniaturized tagmentation-based protocol for efficient sequencing of SARS-CoV-2
Authors: Fuchs Marc , Radulescu Clara , Tang Miao , Mahesh Arun , Lavin Deborah , Umbreen Syed , McKenna James , Smyth Mark , McColgan Eilís , Molnar Zoltan , Baxter Chris , Skvortsov Timofey , Singh Aditi , Rogan Fiona , Miskelly Julia , Bridgett Stephen , Fairley Derek , Simpson David A.
Published: October 2021

Introduction

The COVID-19 pandemic has highlighted the importance of whole genome sequencing (WGS) of SARS-CoV-2 to inform public health policy. By enabling definition of lineages it facilitates tracking of the global spread of the virus. The evolution of new variants can be monitored and knowledge of specific mutations provides insights into the mechanisms through which the virus increases transmissibility or evades immunity. To date almost one million SARS-CoV-2 genomes have been sequenced by members of the COVID-19 Genomics UK (COG-UK) Consortium. To achieve similar feats in a more cost-effective and sustainable manner in future, improved high throughput virus sequencing protocols are required. We have therefore developed a miniaturized library preparation protocol with drastically reduced consumable use and costs.

Methods

SARS-CoV-2 RNA was amplified using the ARTIC nCov-2019 multiplex RT-PCR protocol and purified using a conventional liquid handling system. Acoustic liquid transfer (Echo 525) was employed to reduce reaction volumes and the number of tips required for a Nextera XT library preparation. Sequencing was performed on an Illumina MiSeq.

Results

We present the ‘Mini-XT’ miniaturized tagmentation-based library preparation protocol available on protocols.io (https://dx.doi.org/10.17504/protocols.io.bvntn5en). The final version of Mini-XT has been used to sequence 4,384 SARS-CoV-2 samples from N. Ireland with a COG-UK QC pass rate of 97.4%. Sequencing quality was comparable and lineage calling consistent for replicate samples processed with full volume Nextera DNA Flex (333 samples) or using nanopore technology (20 samples). SNP calling between Mini-XT and these technologies was consistent and sequences from replicate samples paired together in maximum likelihood phylogenetic trees.

Conclusion

The Mini-XT protocol maintains sequence quality while reducing library preparation reagent volumes 8-fold and halving overall tip usage from sample to sequence to provide concomitant cost savings relative to standard protocols. This will enable more efficient high-throughput sequencing of SARS-CoV-2 isolates and future pathogen WGS.
Neonatal outcomes of preterm infants born during COVID-19 community lockdowns in Melbourne, Australia
Authors: Mulcahy Brendan , Rolnik Daniel L. , Matheson Alexia , Liu Yizhen , Palmer Kirsten R. , Mol Ben W. , Malhotra Atul
Published: October 2021

Background

Community lockdowns during the COVID-19 pandemic may influence preterm birth rates, but mechanisms are unclear.

Methods

We compared neonatal outcomes of preterm infants born to mothers exposed to community lockdowns in 2020 (exposed group) to those born in 2019 (control group). Main outcome studied was composite of significant neonatal morbidity or death.

Results

Median gestational age was 35+4 weeks (295 infants, exposed group) vs. 35+0 weeks (347 infants, control group) (p = 0.108). The main outcome occurred in 36/295 (12.2%) infants in exposed group vs. 46/347 (13.3%) in control group (p = 0.69). Continuous positive airway pressure (CPAP) use, jaundice requiring phototherapy, hypoglycaemia requiring treatment, early neonatal white cell and neutrophil counts were significantly reduced in the exposed group.

Conclusions

COVID-19 community lockdowns did not alter composite neonatal outcomes in preterm infants, but reduced rates of some common outcomes, and early white cell and neutrophil counts.
CAMION: a catchment area maximization algorithm, with application to oncology accessibility in metropolitan France
Authors: Daoud Eric , Hamy Anne-Sophie , Dumas Elise , Delrieu Lidia , Rejo Beatriz Grandal , Bihan-Benjamin Christine Le , Houzard Sophie , Bousquet Philippe-Jean , Hotton Judicaël , Savoye Aude-Marie , Jouannaud Christelle , Azencott Chloé-Agathe , Lelarge Marc , Reyal Fabien
Published: October 2021

Background

Access to health services plays a key role in cancer survival. Uneven distributions of populations and health facilities lead to geographical disparities. Location-allocation algorithms can address these disparities by finding new locations and capacities for health facilities. However, in oncology, opening new hospitals or moving them is difficult in practice, and should be handled carefully.

Methods

We propose a method to measure the spatial accessibility to oncology care and identify the hospitals to grow to reduce disparities. We first ran a clustering algorithm to automatically label the hospitals in terms of oncology specialization. Then, we computed an accessibility score to these hospitals for every population location. Finally, we introducedCAMION, an optimization algorithm based on Linear Programming that reduces disparities in oncology accessibility by identifying health facilities that should increase their capacities.

Results

We demonstrate our algorithm in metropolitan France. The clustering step let us identify different oncology specialization levels for hospitals. Most of the population in metropolitan France lived in good accessibility areas, especially in large cities. Lower accessibility zones are often rural or suburban municipalities. The optimization algorithm effectively manages to identify hospitals to grow, based on current oncology specialization and accessibility scores.

Discussion

There is a tradeoff to be found by patients, between care center proximity and care center expertise, which is less likely to happen for patients living in good accessibility areas. The accessibility score is deliberately non-specific to cancer type but can be adapted to more precise pathologies. Our method is replicable in any country, given hospitals and population locations data. We developed a web application intended for healthcare professionals to let them to run the optimization algorithm with the desired parameters and visualize the results.