bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous Hepatogonodal and Splenogonogal Fusion: A Rare Cause of Bilateral Intra-Abdominal Testis in an 18-Month-Old Boy
Authors: Durmuş Gül , Boybeyi-Turer Ozlem , Özcan Hatice Nursun , Gözmen Onur , Demirbilek Hüseyin , Soyer Tutku
Published: June 2022

The fusion of gonadal structures with internal organs is very rare. The close proximity between the left gonad and spleen during embryogenesis may result in splenogonadal fusion (SGF). Moreover, the trapping of hepatocyte-destined mesenchyme cells in gonads is defined as hepatogonadal fusion (HGF). The fusion of gonads with intra-abdominal organs may be continuous and may impair testicular descent during the prenatal period. We herein report an 18-month-old boy presented with bilateral nonpalpable testis due to concomitant continuous HGF and SGF. To our knowledge, this is the first case of concomitant HGF and SGF in a boy with bilateral intra-abdominal testis. Laparoscopic excision of fibrous cords and orchidopexy can be achieved despite continuous fusions.
Larotrectinib as an Effective Therapy in Congenital Infantile Fibrosarcoma: Report of Two Cases
Authors: Lapeña Lucas Moratilla , Caldas Maria Carmen Sarmiento , Ramírez Carla , Basilio María San , Junco Paloma Triana , Rodríguez-Laguna Lara , Martínez-González Victor , Marín-Manzano Elena , Perez-Martinez Antonio , Lopez-Gutierrez Juan Carlos
Published: June 2022

Congenital infantile fibrosarcoma (CIF) is a rare tumor in children that occurs in the first years of life. It usually arises in the extremities but some cases affect the trunk, neck, abdomen, or retroperitoneum. Surgical resection has been traditionally the treatment of choice but the development of genomic analysis and targeted therapies has shed light on new therapeutic options.

We present two patients with a congenital mass, one in the abdominal cavity (1-month-old) and the second in the left lower extremity respectively (2-months-old). In both cases, the clinical and radiological findings showed heterogeneous masses with rapidly progressive growth. MRI in the first patient exhibited an abdominal mass surrounding the aorta and inferior vena cava associated with a giant infrarenal aortic aneurysm. CT-guided biopsy was performed with pathological findings of fibrosarcoma and ETV6-NTRK3 gene fusion. The second patient underwent open biopsy also with histopathological diagnosis of fibrosarcoma and the same mutation in the TRK gene (NTRK3). Targeted therapy with a specific TRK inhibitor, larotrectinib, was started in both patients. Periodical controls were made by ultrasound or MRI, and after a few weeks of treatment, both children showed significant decrease in the mass. By the second and third months after starting the treatment, both tumors disappeared. The first patient is now 15-months-old and the second one is 8-months-old.

Larotrectinib is a novel targeted therapy with excellent results in CIF but long-term outcomes are limited to establish it as a gold standard treatment.
Correlation of ROS1 (D4D6) Immunohistochemistry with ROS1 Fluorescence In Situ Hybridization Assay in a Contemporary Cohort of Pulmonary Adenocarcinomas
Authors: Sharma Shivani , Mishra Sourav K. , Bhardwaj Mohit , Jha Shilpy , Geller Matthew , Dewan Aditi , Jain Ekta , Dixit Mallika , Jain Deepika , Munjal Gauri , Kumar Shivmurti , Mohanty Sambit K.
Published: June 2022

Objective Repressor of Silencing (ROS1) gene rearrangement in the lung adenocarcinomas is one of the targetable mutually exclusive genomic alteration. Fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next-generation sequencing, and reverse transcriptase polymerase chain reaction assays are generally used to detect ROS1 gene alterations. We evaluated the correlation between ROS1 IHC and FISH analysis considering FISH as the gold standard method to determine the utility of IHC as a screening method for lung adenocarcinoma.

Materials and Methods A total of 374 advanced pulmonary adenocarcinoma patients were analyzed for ROS1 IHC on Ventana Benchmark XT platform using D4D6 rabbit monoclonal antibody. FISH assay was performed in parallel in all these cases using the Vysis ROS1 Break Apart FISH probe.

Statistical Analysis The sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, and accuracy were evaluated.

Results A total of 17 tumors were positive either by IHC or FISH analysis or both (true positive). Four tumors were positive by IHC (H-score range: 120–270), while negative on FISH analysis (false positive by IHC). One tumor was IHC negative, but positive by FISH analysis (false negative). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value, and accuracy were 94.4% (confidence interval [CI]: 72.71–99.86%), 63.6% (CI: 30.79–89.07%), 2.6 (CI: 1.18–5.72), 0.09 (CI: 0.01–0.62), 80.95% (CI: 65.86–90.35%), 87.5% (CI: 49.74–98.02%), and 82.76%, respectively.

Conclusion ROS1 IHC has high sensitivity at a cost of lower specificity for the detection of ROS1 gene rearrangement. All IHC positive cases should undergo a confirmatory FISH test as this testing algorithm stands as a reliable and economic tool to screen ROS1 rearrangement in lung adenocarcinomas.
Hybrid Arch Repair with Supra-Aortic Debranching and Using Castor Stent-Graft
Authors: Gao Xijie , Liu Guohong , Lu Jun , Zhao Jianbo
Published: June 2022

Background The management of aortic lesions involving the aortic arch in patients who cannot tolerate thoracotomy is a challenge.

Case Description A 32-year-old woman who underwent a giant aneurysm at the proximal end of the descending aorta with significant vascular wall calcification. The patient underwent Castor single-branched stent-grafting in the brachiocephalic trunk combined with surgical supra-aortic debranching, which avoided surgical aortic arch replacement and stent fenestration.reopening. The patient was followed up for 9 months, and surgery-related complications were not observed.

Conclusion Hybrid arch repair with supra-aortic debranching and using Castor single-branched stent can be used to treat aortic lesions involving the aortic arch.
Intercultural discussion of conceptual universals in discourse: joint online methodology to bring about social change through novel conceptualizations of Covid-19
Authors: Schnell Zsuzsanna , Ervas Francesca
Published: June 2022

The present article addresses the professional conclusions of an international platform of education in intercultural discourse in the European Union’s EDUC Project. In flagging social issues and concerns,cross-cultural academic collaborationis a powerful tool to bring aboutsocial change. In our educational project participants encounter different cultures, so the discussed topics, and especially the metaphors for the Covid-19 pandemic, receive instant reflections fromdifferent cultural perspectives, multiplying the potential sphere of validinterpretations, yielding novel perspectives inintercultural pragmaticsand communication. This gives birth to anovel methodologythat builds on the open-minded integration of different points of view, understanding universal traits of human cognition and differences in culture in the linguistics of discourse.
A novel methodology of international discourse: online joint course across cultures
Authors: Schnell Zsuzsanna , Podeschi Christopher
Published: June 2022

This article explores a novel methodology in the globalized classroom to face and tackle new challenges across cultures. The new online educational form of international discourse has the potential to make a difference in and outside Academia as it encompasses interpersonal communication across cultures and thus offers a novel framework for interpretation of different sociocultural perspectives to bring about social change. It transcends geographical and physical boundaries as it brings people together for discussion in the online joint event. Our study guides the reader through a collaborative educational framework and offers a methodology that transcends boundaries, exemplifying a tool for 21st century education. It offers techniques that bring on social change and enhances open-mindedness in tackling social problems with valuable methods from the fields of humanities and intercultural, collaborative communication.
Zinc and iron application in conjunction with nitrogen for agronomic biofortification of field crops – a review
Authors: Kaur Amandeep , Singh Guriqbal
Published: June 2022

Context Maintaining food and nutritional security for the ever increasing population of the world is a great chllenge. Zinc and iron are important micronutrients for both human health and plant growth. Insufficient intake of these micronutrients leads to their deficiency in human body which causes morbidity and mortality in different age groups of poor populations in developing countries. Aims Therefore, agronomic biofortification is considered the most promising approach to alleviate zinc and iron malnutrition in developing countries. Methods The studies reviewed in this article clearly show that the combined application of zinc and nitrogen, iron and nitrogen, and zinc, iron and nitrogen to the soil or to the foliage during the reproductive phase leads to enhanced nutrient (zinc and iron) content in edible parts of crop plants. This happens as the remobilisation and translocation of zinc, iron and urea are governed by the same genetic pathways inside the plant. Key results The soil/foliar application of micronutrients (zinc and iron) along with nitrogen (mainly through urea) improves not only the micronutrient (zinc and iron) content in edible parts of the crop plants but also the crop productivity, and thus, is a win–win situation for growers as well as consumers. Conclusions Foliar application of urea at 1–2% along with zinc or iron or both during the reproductive phase has been found more effective for biofortification point of view. Implications This article reviews the effects of zinc and iron application in combination with nitrogen on agronomic biofortification in important field crops.
Equal but different! Improving care for older LGBT+ adults
Authors: Bailey Dan , Calasanti Toni , Crowe Andrew , di Lorito Claudio , Hogan Patrick , de Vries Brian
Published: June 2022

International human rights movements have improved the visibility and equality of lesbian, gay, bisexual and transgender+ (LGBT+) communities and their members. Health outcomes for LGBT+ people remain, however, worse than for their non-LGBT+ peers. Older LGBT+ people have experienced fewer positive changes, in part due to their lived experience of discrimination and their ongoing, unintentional invisibility in medical and social care. This article highlights the impacts of societal structure, health and social care on the lives of older LGBT+ people including physical and mental health, End of Life, Dementia, Housing and Care Settings, and a focus on the experiences of trans-people. We look at the existing improvements developed by LGBT+ communities (and their allies) and propose refreshing Person-Centred Care to improve inclusivity. Finally, we provide a framework for looking at the areas in which service challenges arise and suggest ways to address these to make health and social care services more ready to meet the needs of older LGBT+ people.
‘Normative Facts as Reasons’
Authors: Molina Yohan
Published: June 2022

In ‘Normative Facts and Reasons’, Fabienne Peter proposes that there are two different types of practical warrant, which she terms ‘entitlement warrant’ and ‘reason-based justification’. This thesis relies fundamentally on her distinction between normative facts and normative reasons. I will raise two general critical observations. First, I will claim that Peter advocates a representation-dependent conception of reasons that is at odds with an intuitive and accepted understanding of them. Second, I will contend that reasons need not be the entities we directly handle in our deliberations, which undermines the idea that reasons are propositions. In this way, her distinction fails: normative reasons are just normative facts. This implies that the existence of two types of practical warrant, based either on normative facts or reasons, is unfounded.
ggtranscript: an R package for the visualization and interpretation of transcript isoforms usingggplot2
Authors: Gustavsson Emil K , Zhang David , Reynolds Regina H , Garcia-Ruiz Sonia , Ryten Mina
Published: June 2022

Motivation

The advent of long-read sequencing technologies has increased demand for the visualization and interpretation of transcripts. However, tools that perform such visualizations remain inflexible and lack the ability to easily identify differences between transcript structures. Here, we introduce ggtranscript, an R package that provides a fast and flexible method to visualize and compare transcripts. As a ggplot2 extension, ggtranscript inherits the functionality and familiarity of ggplot2 making it easy to use.

Availability and implementation

ggtranscript is an R package available at https://github.com/dzhang32/ggtranscript (DOI: https://doi.org/10.5281/zenodo.6374061) via an open-source MIT licence. Further documentation is available at https://dzhang32.github.io/ggtranscript/.
CancerCellTracker: a brightfield time-lapse microscopy framework for cancer drug sensitivity estimation
Authors: Jiang Qibing , Sudalagunta Praneeth , Silva Maria C , Canevarolo Rafael R , Zhao Xiaohong , Ahmed Khandakar Tanvir , Alugubelli Raghunandan Reddy , DeAvila Gabriel , Tungesvik Alexandre , Perez Lia , Gatenby Robert A , Gillies Robert J , Baz Rachid , Meads Mark B , Shain Kenneth H , Silva Ariosto S , Zhang Wei
Published: June 2022

Motivation

Time-lapse microscopy is a powerful technique that relies on images of live cells cultured ex vivo that are captured at regular intervals of time to describe and quantify their behavior under certain experimental conditions. This imaging method has great potential in advancing the field of precision oncology by quantifying the response of cancer cells to various therapies and identifying the most efficacious treatment for a given patient. Digital image processing algorithms developed so far require high-resolution images involving very few cells originating from homogeneous cell line populations. We propose a novel framework that tracks cancer cells to capture their behavior and quantify cell viability to inform clinical decisions in a high-throughput manner.

Results

The brightfield microscopy images a large number of patient-derived cells in an ex vivo reconstruction of the tumor microenvironment treated with 31 drugs for up to 6 days. We developed a robust and user-friendly pipeline CancerCellTracker that detects cells in co-culture, tracks these cells across time and identifies cell death events using changes in cell attributes. We validated our computational pipeline by comparing the timing of cell death estimates by CancerCellTracker from brightfield images and a fluorescent channel featuring ethidium homodimer. We benchmarked our results using a state-of-the-art algorithm implemented in ImageJ and previously published in the literature. We highlighted CancerCellTracker’s efficiency in estimating the percentage of live cells in the presence of bone marrow stromal cells.

Availability and implementation

https://github.com/compbiolabucf/CancerCellTracker.

Supplementary information

Supplementary data are available at Bioinformatics online.
ClearCNV: CNV calling from NGS panel data in the presence of ambiguity and noise
Authors: May Vinzenz , Koch Leonard , Fischer-Zirnsak Björn , Horn Denise , Gehle Petra , Kornak Uwe , Beule Dieter , Holtgrewe Manuel
Published: June 2022

Motivation

While the identification of small variants in panel sequencing data can be considered a solved problem, the identification of larger, multi-exon copy number variants (CNVs) still poses a considerable challenge. Thus, CNV calling has not been established in all laboratories performing panel sequencing. At the same time, such laboratories have accumulated large datasets and thus have the need to identify CNVs on their data to close the diagnostic gap.

Results

In this article, we present our method clearCNV that addresses this need in two ways. First, it helps laboratories to properly assign datasets to enrichment kits. Based on homogeneous subsets of data, clearCNV identifies CNVs affecting the targeted regions. Using real-world datasets and validation, we show that our method is highly competitive with previous methods and preferable in terms of specificity.

Availability and implementation

The software is available for free under a permissible license at https://github.com/bihealth/clear-cnv.

Supplementary information

Supplementary data are available at Bioinformatics online.
Predicting RNA distance-based contact maps by integrated deep learning on physics-inferred secondary structure and evolutionary-derived mutational coupling
Authors: Singh Jaswinder , Paliwal Kuldip , Litfin Thomas , Singh Jaspreet , Zhou Yaoqi
Published: June 2022

Motivation

Recently, AlphaFold2 achieved high experimental accuracy for the majority of proteins in Critical Assessment of Structure Prediction (CASP 14). This raises the hope that one day, we may achieve the same feat for RNA structure prediction for those structured RNAs, which is as fundamentally and practically important similar to protein structure prediction. One major factor in the recent advancement of protein structure prediction is the highly accurate prediction of distance-based contact maps of proteins.

Results

Here, we showed that by integrated deep learning with physics-inferred secondary structures, co-evolutionary information and multiple sequence-alignment sampling, we can achieve RNA contact-map prediction at a level of accuracy similar to that in protein contact-map prediction. More importantly, highly accurate prediction for top L long-range contacts can be assured for those RNAs with a high effective number of homologous sequences (Neff > 50). The initial use of the predicted contact map as distance-based restraints confirmed its usefulness in 3D structure prediction.

Availability and implementation

SPOT-RNA-2D is available as a web server at https://sparks-lab.org/server/spot-rna-2d/ and as a standalone program at https://github.com/jaswindersingh2/SPOT-RNA-2D.

Supplementary information

Supplementary data are available at Bioinformatics online.
Clinical value of the expression levels of protein tyrosine phosphatase non-receptor type 22.6 mRNA in peripheral blood mononuclear cells in Crohn’s disease
Authors: Hu Mei , Chen Zhitao , Liao Yusheng , Wu Jie , Zheng Dan , Zhang Heng
Published: June 2022

Objective

To explore the relationship between the expression levels of protein tyrosine phosphatase non-receptor type (PTPN) 22.6 mRNA in peripheral blood mononuclear cells (PBMCs) and the disease activity as well as clinical characteristics in Crohn’s disease (CD) patients.

Methods

A total of 480 subjects were enrolled. Data were collected including baseline information, expression levels of PTPN22.6 mRNA in PBMCs for all subjects, C-reactive protein (CRP) levels in serum, clinical characteristics, and disease activity for all patients. Expression levels of PTPN22.6 mRNA in PBMCs, CRP levels in serum, clinical characteristics according to Montreal Classification [8], and Crohn’s disease activity index (CDAI) were the primary observation outcomes.

Results

The expression levels of PTPN22.6 mRNA (P = 0.032) in PBMCs and serum CRP levels (P < 0.001) were significantly higher in active CD patients than in inactive CD patients (P = 0.032). Correlation analysis showed that there was a positive correlation between expression levels of PTPN22.6 mRNA and CDAI value (r = 0.512, P = 0.003), as well as expression levels of PTPN22.6 mRNA and CRP levels in the CD group (r = 0.456, P = 0.006). There were significantly higher expression levels of PTPN22.6 mRNA in PBMCs in patients with structuring behavior than that in patients with non-stricturing and non-penetrating (NSNP) behaviors (P = 0.018) and penetrating behaviors (P = 0.024).

Conclusions

The expression levels of PTPN22.6 mRNA can be used as an indicator to help predict CD diagnosis, disease activity, serum CRP level, and behavior type of CD disease.
The genome of Prunus humilis provides new insights to drought adaption and population diversity
Authors: Wang Yi , Xie Jun , Zhang HongNa , Li Weidong , Wang Zhanjun , Li Huayang , Tong Qian , Qiao Gaixia , Liu Yujuan , Tian Ying , Wei Yong Zan , Li Ping , Wang Rong , Cheng Weiping , Liang Zhengchang , Xu Meilong
Published: June 2022

Prunus humilis (2n = 2x = 16) is a dwarf shrub fruit tree native to China and distributed widely in the cold and arid northern region. In this study, we obtained the whole genome sequences of P. humilis by combining Illumina, PacBio and HiC sequencing technologies. This genome was 254.38 Mb long and encodes 28,301 putative proteins. Phylogenetic analysis indicated that P. humilis shares the same ancestor with Prunus mume and Prunus armeniaca at ∼ 29.03 Mya. Gene expansion analysis implied that the expansion of WAX-related and LEA genes might be associated with high drought tolerance of P. humilis and LTR maybe one of the driver factors for the drought adaption by increase the copy number of LEAs. Population diversity analysis among 20 P. humilis accessions found that the genetic diversity of P. humilis populations was limited, only 1.40% base pairs were different with each other, and more wild resources need to be collected and utilized in the breeding and improvement. This study provides new insights to the drought adaption and population diversity of P. humilis that could be used as a potential model plant for horticultural research.
Chromosome-level genome assembly of the aquatic plant Nymphoides indica reveals transposable element bursts and NBS-LRR gene family expansion shedding light on its invasiveness
Authors: Yang Jing-Shan , Qian Zhi-Hao , Shi Tao , Li Zhi-Zhong , Chen Jin-Ming
Published: June 2022

Nymphoides indica, an aquatic plant, is an invasive species that causes both ecological and economic damage in North America and elsewhere. However, the lack of genomic data of N. indica limits the in-depth analysis of this invasive species. Here, we report a chromosome-level genome assembly of nine pseudochromosomes of N. indica with a total size of ∼ 520 Mb. More than half of the N. indica genome consists of transposable elements (TEs), and a higher density of TEs around genes may play a significant role in response to an ever-changing environment by regulating the nearby gene. Additionally, our analysis revealed that N. indica only experienced a gamma (γ) whole-genome triplication event. Functional enrichment of the N. indica-specific and expanded gene families highlighted genes involved in the responses to hypoxia and plant–pathogen interactions, which may strengthen the ability to adapt to external challenges and improve ecological fitness. Furthermore, we identified 160 members of the nucleotide-binding site and leucine-rich repeat gene family, which may be linked to the defence response. Collectively, the high-quality N. indica genome reported here opens a novel avenue to understand the evolution and rapid invasion of Nymphoides spp.
Environmental Inequality in Four European Cities: A Study Combining Household Survey and Geo-Referenced Data
Authors: Diekmann Andreas , Bruderer Enzler Heidi , Hartmann Jörg , Kurz Karin , Liebe Ulf , Preisendörfer Peter
Published: June 2022

Combining individual-level survey data and geo-referenced administrative noise data for four European cities (Bern, Zurich, Hanover, and Mainz; n = 7,450), we test the social gradient hypothesis, which states that exposure to residential noise is higher for households in a lower socioeconomic position (measured by income and migration background). In addition, we introduce and test the ‘environmental shielding hypothesis’, which states that, given environmental ‘bads’ in the neighbourhood, privileged social groups have better opportunities to shield themselves against them. Our results show that, for many residents of the four cities, observed road traffic and aircraft noise levels are above World Health Organization limits. Estimates of spatial error regression models only partly support the social gradient hypothesis. While we find significant but relatively small income effects and somewhat stronger effects of having a (non-Western) migration background, these effects are not significant in all cities. However, especially high-income households are more capable of avoiding exposure to indoor noise. Due to their residence characteristics and having the resources to maintain high standards of noise protection, these households have more capabilities to shield themselves against environmental bads in their neighbourhood. This supports the environmental shielding hypothesis.
Rivaroxaban and aspirin vs. aspirin alone in Asian compared with non-Asian patients with chronic coronary artery disease or peripheral arterial disease: the COMPASS trial
Authors: Hori Masatsugu , Zhu Jun , Liang Yan , Bhatt Deepak L , Bosch Jackie , Connolly Stuart J , Fox Keith A A , Maggioni Aldo , Yusuf Salim , Eikelboom John W
Published: June 2022

Aims

It is unknown whether Asian and non-Asian patients with atherosclerotic vascular disease derive similar benefits from long-term antithrombotic therapy.

Methods and results

In patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in The Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, the effects of rivaroxaban 2.5 mg b.i.d. plus aspirin 100 mg o.d. were compared with those of aspirin 100 mg o.d. in Asian vs. non-Asian patients (race was self-identified). Asians (n = 4269) vs. non-Asians (n = 23 126) had similar rates of major adverse cardiovascular events (MACEs) (4.85% vs. 4.83%, P = 0.30) and modified International Society on Thrombosis and Haemostasis (ISTH) major bleeding (2.72% vs. 2.58%, P = 0.22), but higher rates of intracranial haemorrhage (ICH) (0.63% vs. 0.29%, P = 0.01) and minor bleeding (13.61% vs. 6.49%, P < 0.001). In Asians vs. non-Asians, the combination of rivaroxaban and aspirin compared with aspirin alone produced consistent reductions in MACE [Asians: hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.45–0.90; non-Asians: HR: 0.78, 95% CI: 0.67–0.90; P(heterogeneity) = 0.29], increases in modified ISTH major bleeding (Asians: HR 2.24, 95% CI: 1.40–3.58; non-Asians: HR: 1.60, 95% CI: 1.30–1.97; P = 0.20), and net clinical outcome (Asians: HR: 0.77, 95% CI: 0.56–1.05; non-Asians: HR: 0.81, 95% CI: 0.70–0.93, P = 0.78), but borderline higher rates of ICH (Asians: HR: 3.50, 95% CI: 0.98–12.56; non-Asians: HR: 0.81, 95% CI: 0.43, 1.53; P = 0.04).

Conclusion

Asian compared with non-Asian patients with chronic CAD and/or PAD have higher rates of ICH and minor bleeding. The combination of rivaroxaban and aspirin vs. aspirin alone produces similar effects for MACE, modified ISTH major bleeding, and net clinical outcome but may be associated with higher rates of ICH in Asian patients.
Polygenic risk score for ACE-inhibitor-associated cough based on the discovery of new genetic loci
Authors: Ghouse Jonas , Tragante Vinicius , Muhammad Ayesha , Ahlberg Gustav , Skov Morten W , Roden Dan M , Jonsdottir Ingileif , Andreasen Laura , Lundegaard Pia Rengtved , Trudsø Linea C , Banasik Karina , Brunak Søren , Ostrowski Sisse R ,   eMERGE consortium, Torp-Pedersen Christian , Pedersen Ole V , Sørensen Erik , Køber Lars , Iversen Kasper , Thorsteinsdottir Unnur , Thorgeirsson Gudmundur , Ullum Henrik , Gudbjartsson Daniel F , Mosley Jonathan D , Holm Hilma , Stefansson Kari , Bundgaard Henning , Olesen Morten Salling
Published: June 2022

Aims

To search for sequence variants associated with ACEi discontinuation and to test their association with ACEi-associated adverse drug reactions (ADRs).

Methods and results

A genome-wide association study (GWAS) on ACEi discontinuation was conducted, including 33 959 ACEi-discontinuers and 44 041 controls. Cases were defined as persons who switched from an ACEi treatment to an angiotensin receptor blocker. Controls were defined as persons who continued ACEi treatment for at least 1 year. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed for ACEi discontinuation risk by mixed model regression analysis. Summary statistics from the individual cohorts were meta-analyzed with a fixed-effects model. To test for association with specific ACEi-associated ADRs, any genome-wide significant (P < 5 × 10-8) ACEi discontinuation variants was tested for association with ACEi-associated cough and angioedema. A polygenetic risk score (PRS) based on ACEi discontinuation GWAS data was constructed and tested for association with ACEi-associated cough and angioedema in two population-based samples. In total, seven genetic genome-wide loci were identified, of which six were previously unreported. The strongest association with ACEi discontinuation was at 20q13.3 (NTSR1; OR: 1.21; 95% CI: 1.17–1.24; P = 2.1 × 10–34). Five of seven lead variants were associated with ACEi-associated cough, whereas none were associated with ACEi-associated angioedema. The ACEi discontinuation PRS was associated with ACEi-associated cough in a dose–response manner but not with ACEi-associated angioedema. ACEi discontinuation was genetically correlated with important causes for cough, including gastro-esophageal reflux disease, allergic rhinitis, hay fever, and asthma, which indicates partly shared genetic underpinning between these traits.

Conclusion

This study showed the advantage of using prescription patterns to discover genetic links with ADRs. In total, seven genetic loci that associated with ACEi discontinuation were identified. There was evidence of a strong association between our ADR phenotype and ACEi-associated cough. Taken together, these findings increase insight into the pathophysiological processes that underlie ACEi-associated ADRs.
Identification of occupations susceptible to high exposure and risk associated with multiple toxicants in an observational study: National Health and Nutrition Examination Survey 1999–2014
Authors: Nguyen Vy Kim , Colacino Justin , Patel Chirag J , Sartor Maureen , Jolliet Olivier
Published: June 2022

Occupational exposures to toxicants are estimated to cause over 370 000 premature deaths annually. The risks due to multiple workplace chemical exposures and those occupations most susceptible to the resulting health effects remain poorly characterized. The aim of this study is to identify occupations with elevated toxicant biomarker concentrations and increased health risk associated with toxicant exposures in a diverse working US population. For this observational study of 51 008 participants, we used data from the 1999–2014 National Health and Nutrition Examination Survey. We characterized differences in chemical exposures by occupational group for 131 chemicals by applying a series of generalized linear models with the outcome as biomarker concentrations and the main predictor as the occupational groups, adjusting for age, sex, race/ethnicity, poverty income ratio, study period, and biomarker of tobacco use. For each occupational group, we calculated percentages of participants with chemical biomarker levels exceeding acceptable health-based guidelines. Blue-collar workers from “Construction,” “Professional, Scientific, Technical Services,” “Real Estate, Rental, Leasing,” “Manufacturing,” and “Wholesale Trade” have higher biomarker levels of toxicants such as several heavy metals, acrylamide, glycideamide, and several volatile organic compounds (VOCs) compared with their white-collar counterparts. Moreover, blue-collar workers from these industries have toxicant concentrations exceeding acceptable levels: arsenic (16%–58%), lead (1%–3%), cadmium (1%–11%), glycideamide (3%–6%), and VOCs (1%–33%). Blue-collar workers have higher toxicant levels relative to their white-collar counterparts, often exceeding acceptable levels associated with noncancer effects. Our findings identify multiple occupations to prioritize for targeted interventions and health policies to monitor and reduce toxicant exposures.
A chromosome-level genome assembly of the orange wheat blossom midge,Sitodiplosis mosellanaGéhin (Diptera: Cecidomyiidae) provides insights into the evolution of a detoxification system
Authors: Gong Zhongjun , Li Tong , Miao Jin , Duan Yun , Jiang Yueli , Li Huiling , Guo Pei , Wang Xueqin , Zhang Jing , Wu Yuqing
Published: June 2022

The orange wheat blossom midge Sitodiplosis mosellana Géhin (Diptera: Cecidomyiidae), an economically important pest, has caused serious yield losses in most wheat-growing areas worldwide in the past half-century. A high-quality chromosome-level genome for S. mosellana was assembled using PacBio long read, Illumina short read, and Hi-C sequencing technologies. The final genome assembly was 180.69 Mb, with contig and scaffold N50 sizes of 998.71 kb and 44.56 Mb, respectively. Hi-C scaffolding reliably anchored 4 pseudochromosomes, accounting for 99.67% of the assembled genome. In total, 12,269 protein-coding genes were predicted, of which 91% were functionally annotated. Phylogenetic analysis indicated that S. mosellana and its close relative, the swede midge Contarinia nasturtii, diverged about 32.7 MYA. The S. mosellana genome showed high chromosomal synteny with the genome of Drosophila melanogaster and Anopheles gambiae. The key gene families involved in the detoxification of plant secondary chemistry were analyzed. The high-quality S. mosellana genome data will provide an invaluable resource for research in a broad range of areas, including the biology, ecology, genetics, and evolution of midges, as well as insect–plant interactions and coevolution.
The Impact of a Virtual Art Tour Intervention on the Emotional Well-Being of Older Adults
Authors: Averbach Julie , Monin Joan
Published: June 2022

Background and Objectives

Based on empirical support for the public health value of art-viewing, the present study examines the impact of a novel virtual art tour intervention on the emotional well-being of older adults.

Research Design and Methods

We used a pre–post quantitative survey design to evaluate an art tour intervention delivered to older adults (N = 155) directly in their homes and community centers. Emotion was measured using the modified Differential Emotions Scale, and life satisfaction was measured with the Satisfaction with Life Scale. To gain insight into participants’ experiences during the tours, we also conducted qualitative interviews with program coordinators at partnering organizations who viewed the tours with participants.

Results

Following the art tours, participants reported significant improvements in positive emotions (especially awe) and life satisfaction. There were no significant effects on negative emotions. Program coordinators provided feedback that the tour was engaging, intellectually stimulating, and enjoyable for participants.

Discussion and Implications

Findings support the beneficial mental health potential of virtual art-viewing experiences for older adults. Technology may provide an effective platform to deliver wellness-oriented cultural enrichment programming while addressing accessibility barriers linked to in-person arts engagement.
Surgical Management of Enterovesical Fistula in Crohn’s Disease in the Biologic Era
Authors: McKenna Nicholas P , Kelley Scott R , Bews Katherine A , Behm Kevin T , Mathis Kellie L
Published: June 2022

Lay Summary

Enterovesical fistula in Crohn’s disease that require surgery may be managed safely laparoscopically with similar morbidity to open repair and a shorter length of stay. Preoperative biologic exposure does not affect surgical morbidity.
Association between urinary polycyclic aromatic hydrocarbon metabolites and diabetes mellitus among the US population: a cross-sectional study
Authors: Mallah Manthar Ali , Basnet Til Bahadur , Ali Mukhtiar , Xie Fuwei , Li Xiang , Feng Feifei , Wang Wei , Shang Pingping , Zhang Qiao
Published: June 2022

Background

The primary aim of this study is to examine the association between urinary polycyclic aromatic hydrocarbons (PAHs) and diabetes mellitus (DM) among the US population.

Methods

We used data from the National Health and Nutritional Examination Survey 2003–16, which is a nationally representative population-based survey of the US non-institutionalized population. Logistic regression analysis was performed to evaluate the association between urinary PAHs and the prevalence of DM using odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The study sample including 13 792 individuals ≥18 y of age. The average ages of the three PAH tertiles were 42.56±19.67, 42.21±19.51 and 43.39±17.99 y. An increased risk of DM was found with increased odds for the second (OR 1.56 [95% CI 1.36 to 1.79]) and third tertile (OR 1.79 [95% CI 1.55 to 2.06)] of urinary PAH as compared with the first tertile. Similarly, higher chances of DM were observed in the second (men: OR 1.42 [95% CI 1.18 to 1.71]; women: OR 1.76 [95% CI 1.44 to 2.14]) and third tertile (men: OR 1.69 [95% CI 1.38 to 2.08]; women: OR 1.79 [95% CI 1.46 to 2.19]) of urinary PAHs as compared with the first tertile in both men and women.

Conclusions

A population-based cross-sectional study found a positive association between urinary PAHs and DM in the US population.
Impact of artificial intelligence on pathologists’ decisions: an experiment
Authors: Meyer Julien , Khademi April , Têtu Bernard , Han Wencui , Nippak Pria , Remisch David
Published: June 2022

Objective

The accuracy of artificial intelligence (AI) in medicine and in pathology in particular has made major progress but little is known on how much these algorithms will influence pathologists’ decisions in practice. The objective of this paper is to determine the reliance of pathologists on AI and to investigate whether providing information on AI impacts this reliance.

Materials and Methods

The experiment using an online survey design. Under 3 conditions, 116 pathologists and pathology students were tasked with assessing the Gleason grade for a series of 12 prostate biopsies: (1) without AI recommendations, (2) with AI recommendations, and (3) with AI recommendations accompanied by information about the algorithm itself, specifically algorithm accuracy rate and algorithm decision-making process.

Results

Participant responses were significantly more accurate with the AI decision aids than without (92% vs 87%, odds ratio 13.30, P < .01). Unexpectedly, the provision of information on the algorithm made no significant difference compared to AI without information. The reliance on AI correlated with general beliefs on AI’s usefulness but not with particular assessments of the AI tool offered. Decisions were made faster when AI was provided.

Discussion

These results suggest that pathologists are willing to rely on AI regardless of accuracy or explanations. Generalization beyond the specific tasks and explanations provided will require further studies.

Conclusion

This study suggests that the factors that influence the reliance on AI differ in practice from beliefs expressed by clinicians in surveys. Implementation of AI in prospective settings should take individual behaviors into account.
Predicting COVID-19 county-level case number trend by combining demographic characteristics and social distancing policies
Authors: Li Megan Mun , Pham Anh , Kuo Tsung-Ting
Published: June 2022

Objective

Predicting daily trends in the Coronavirus Disease 2019 (COVID-19) case number is important to support individual decisions in taking preventative measures. This study aims to use COVID-19 case number history, demographic characteristics, and social distancing policies both independently/interdependently to predict the daily trend in the rise or fall of county-level cases.

Materials and Methods

We extracted 2093 features (5 from the US COVID-19 case number history, 1824 from the demographic characteristics independently/interdependently, and 264 from the social distancing policies independently/interdependently) for 3142 US counties. Using the top selected 200 features, we built 4 machine learning models: Logistic Regression, Naïve Bayes, Multi-Layer Perceptron, and Random Forest, along with 4 Ensemble methods: Average, Product, Minimum, and Maximum, and compared their performances.

Results

The Ensemble Average method had the highest area-under the receiver operator characteristic curve (AUC) of 0.692. The top ranked features were all interdependent features.

Conclusion

The findings of this study suggest the predictive power of diverse features, especially when combined, in predicting county-level trends of COVID-19 cases and can be helpful to individuals in making their daily decisions. Our results may guide future studies to consider more features interdependently from conventionally distinct data sources in county-level predictive models. Our code is available at: https://doi.org/10.5281/zenodo.6332944.
Impact of increasing standardized ileal digestible valine: lysine in diets containing 30% dried distiller grains with solubles on growing pig performance
Authors: Clizer David A , Tostenson Blair J , Tauer Sam K , Samuel Ryan S , Cline Paul M
Published: June 2022

A total of 2,430 pigs (DNA 600 × Topigs Norsvin 70, initially 39.4 kg) were used in a 28-d trial to determine the standardized ileal digestible (SID) Val:Lys requirement for pigs fed with diets containing 30% DDGS. Treatments included five diets containing 30% DDGS with SID Val:Lys ratios of 60%, 65%, 70%, 75%, and 80%, plus a corn soybean meal (SBM) diet, for a total of six dietary treatments. Diets were formulated to be isocaloric through the inclusion of fat and to contain equal amounts of SID Lys within phase. Pens were assigned to dietary treatment in a randomized complete block design with initial body weight (BW) as the random blocking factor. Each dietary treatment was replicated 15 times and pens contained 27 pigs, balanced for sex. Increasing the SID Val:Lys ratio in diets containing 30% DDGS increased (Quadratic; P ≤ 0.007) 14-d BW, final BW, average daily gain (ADG), average daily feed intake (ADFI), and gain:feed (G:F) for all periods. Providing an SID Val:Lys ratio of 75% resulted in the heaviest 14-d BW and final BW as well as greater ADG and ADFI of pigs fed with 30% DDGS for all periods. The G:F response was maximized when an SID Val:Lys ratio of 70% was provided from day 0 to 14 while an SID Val:Lys ratio of 75% maximized G:F from day 14 to 28 and for the cumulative period. The SID Val:Lys requirement was estimated at 66.6% (95% CI [65.9, 67.4]), 65.7 (95% CI: [64.8, 66.5]), and 68.4% (95% CI [66.0, 70.8]) for ADG, ADFI, and G:F, respectively, using the straight broken line (SBL) method and 69.9% (95% CI [68.2, 71.5]), 67.6 (95% CI [65.4, 69.8]), and 72.8% (95% CI [69.8, 75.8]) for the quadratic broken line (QBL) method. Pigs fed the corn–SBM diet had heavier 14-d BW, final BW, and greater ADG, ADFI, G:F (P ≤ 0.032) compared to pigs fed diets containing 30% DDGS, except for cumulative ADFI compared to pigs receiving 75% SID Val:Lys (P = 0.167). In conclusion, these results suggest that when feeding 30% DDGS during the growing period, an SID Val:Lys ratio of 68% would yield more than 99% and 97% of the maximum ADG and G:F response for the 39 to 68 kg pigs. However, growth performance of pigs fed diets containing 30% DDGS did not equate to pigs consuming the corn–SBM diet regardless of the SID Val:Lys ratio.
Globularia arabicaMethanolic Leaf Extract Has Higher Efficacy on Burn Wound Healing in Diabetic Rats Compared toMalva slyvestriesMethanolic Leaf Extract
Authors: Alsarayreh Ahmad Z , Khleifat Khaled M , Al-Dalain Sa’ed M , Al-Saraireh Yousef M , Al Qaisi Yaseen T , Alfarrayeh Ibrahim I , AL-Qaraleh Samer Y
Published: June 2022

This study aimed to see how effective Globularia arabica and Malva slyvestries-based cream formulations were at healing scald burn wounds in rats. Depending on ointment, preparations of 1%, 5%, and 10% w/w were created. For comparison, an ointment base and a regular burn cream composed soframycine were utilized. Rats introduced a burn by solidifying equipment at 100°C on a 14-mm2 shaved dorsal region. A deep second-degree burn was created, and the percentage of wound contraction was measured over the next 15 days. The rats were euthanized on days 8 and 15, and histological slides were prepared using hematoxylin and eosin staining. Compared to the control group, there was a substantial increase in wound contraction and a significant decrease in the duration of epithelialization in the based ointment-treated groups. However, as paralleled to Globularia arabica, significant (P < .05) results were observed with 10% Globularia arabica cream, whereas Malva slyverstries indicate minimal healing. Soframycine causes a substantial increase in wound contraction (P < .05). Soframycine cream with 10% Globularia arabica therapy resulted in practically complete re-epithelialization and re-structuring of wound tissue on histological examination, whereas Malva slyversries treatment resulted in low epithelization during treatment days. The findings suggest that Globularia arabica-based cream has the wound-healing capability.
Olfactory Bulb Amyloid-β Correlates With Brain Thal Amyloid Phase and Severity of Cognitive Impairment
Authors: Tremblay Cécilia , Serrano Geidy E , Intorcia Anthony J , Mariner Monica R , Sue Lucia I , Arce Richard A , Atri Alireza , Adler Charles H , Belden Christine M , Shill Holly A , Driver-Dunckley Erika , Mehta Shyamal H , Beach Thomas G
Published: June 2022

The Alzheimer disease (AD) neuropathological hallmarks amyloid β (Aβ) and tau neurofibrillary (NF) pathology have been reported in the olfactory bulb (OB) in aging and in different neurodegenerative diseases, which coincides with frequently reported olfactory dysfunction in these conditions. To better understand when the OB is affected in relation to the hierarchical progression of Aβ throughout the brain and whether OB pathology might be an indicator of AD severity, we assessed the presence of OB Aβ and tau NF pathology in an autopsy cohort of 158 non demented control and 173 AD dementia cases. OB Aβ was found in less than 5% of cases in lower Thal phases 0 and 1, in 20% of cases in phase 2, in 60% of cases in phase 3 and in more than 80% of cases in higher Thal phases 4 and 5. OB Aβ and tau pathology significantly predicted a Thal phase greater than 3, a Braak NF stage greater than 4, and an MMSE score lower than 24. While OB tau pathology is almost universal in the elderly and therefore is not a good predictor of AD severity, OB Aβ pathology coincides with clinically-manifest AD and might prove to be a useful biomarker of the extent of brain spread of both amyloid and tau pathology.