bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic Insights into Genetic Diploidization in the Homosporous Fern Adiantum nelumboides
Authors: Zhong Yan , Liu Yongbo , Wu Wei , Chen Jingfang , Sun Chenyu , Liu Hongmei , Shu Jiangping , Ebihara Atsushi , Yan Yuehong , Zhou Renchao , Schneider Harald 
Published: August 2022

Abstract
Whole-genome duplication has been recognized as a major process in speciation of land plants, especially in ferns. Whereas genome downsizing contributes greatly to the post-genome shock responses of polyploid flowering plants, diploidization of polyploid ferns diverges by maintaining most of the duplicated DNA and is thus expected to be dominated by genic processes. As a consequence, fern genomes provide excellent opportunities to study ecological speciation enforced by expansion of protein families via polyploidy. To test the key predictions of this hypothesis, we reported the de novo genome sequence of Adiantum nelumboides, a tetraploid homosporous fern. The obtained draft genome had a size of 6.27 Gb assembled into 11,767 scaffolds with the contig N50 of 1.37 Mb. Repetitive DNA sequences contributed with about 81.7%, a remarkably high proportion of the genome. With 69,568, the number of predicted protein-coding genes exceeded those reported in most other land plant genomes. Intragenomic synteny analyses recovered 443 blocks with the average block size of 1.29 Mb and the average gene content of 16 genes. The results are consistent with the hypothesis of high ancestral chromosome number, lack of substantial genome downsizing, and dominance of genic diploidization. As expected in the calciphilous plants, a notable number of detected genes were involved in calcium uptake and transport. In summary, the genome sequence of a tetraploid homosporous fern not only provides access to a genomic resource of a derived fern, but also supports the hypothesis of maintenance of high chromosome numbers and duplicated DNA in young polyploid ferns.
Diploid-associated adaptation to chronic low-dose UV irradiation requires homologous recombination in Saccharomyces cerevisiae
Authors: Shibata Mana , Keyamura Kenji , Shioiri Takuya , Noda Shunsuke , Akanuma Genki , Hishida Takashi 
Published: August 2022

Abstract
Ultraviolet-induced DNA lesions impede DNA replication and transcription and are therefore a potential source of genome instability. Here, we performed serial transfer experiments on nucleotide excision repair-deficient (rad14Δ) yeast cells in the presence of chronic low-dose ultraviolet irradiation, focusing on the mechanisms underlying adaptive responses to chronic low-dose ultraviolet irradiation. Our results show that the entire haploid rad14Δ population rapidly becomes diploid during chronic low-dose ultraviolet exposure, and the evolved diploid rad14Δ cells were more chronic low-dose ultraviolet-resistant than haploid cells. Strikingly, single-stranded DNA, but not pyrimidine dimer, accumulation is associated with diploid-dependent fitness in response to chronic low-dose ultraviolet stress, suggesting that efficient repair of single-stranded DNA tracts is beneficial for chronic low-dose ultraviolet tolerance. Consistent with this hypothesis, homologous recombination is essential for the rapid evolutionary adaptation of diploidy, and rad14Δ cells lacking Rad51 recombinase, a key player in homologous recombination, exhibited abnormal cell morphology characterized by multiple RPA–yellow fluorescent protein foci after chronic low-dose ultraviolet exposure. Furthermore, interhomolog recombination is increased in chronic low-dose ultraviolet-exposed rad14Δ diploids, which causes frequent loss of heterozygosity. Thus, our results highlight the importance of homologous recombination in the survival and genomic stability of cells with unrepaired lesions.
Benchmarking ultra-high molecular weight DNA preservation methods for long-read and long-range sequencing
Authors: Dahn Hollis A , Mountcastle Jacquelyn , Balacco Jennifer , Winkler Sylke , Bista Iliana , Schmitt Anthony D , Pettersson Olga Vinnere , Formenti Giulio , Oliver Karen , Smith Michelle , Tan Wenhua , Kraus Anne , Mac Stephen , Komoroske Lisa M , Lama Tanya , Crawford Andrew J , Murphy Robert W , Brown Samara , Scott Alan F , Morin Phillip A , Jarvis Erich D , Fedrigo Olivier 
Published: August 2022

Abstract

Background
Studies in vertebrate genomics require sampling from a broad range of tissue types, taxa, and localities. Recent advancements in long-read and long-range genome sequencing have made it possible to produce high-quality chromosome-level genome assemblies for almost any organism. However, adequate tissue preservation for the requisite ultra-high molecular weight DNA (uHMW DNA) remains a major challenge. Here we present a comparative study of preservation methods for field and laboratory tissue sampling, across vertebrate classes and different tissue types.

Results
We find that storage temperature was the strongest predictor of uHMW fragment lengths. While immediate flash-freezing remains the sample preservation gold standard, samples preserved in 95% EtOH or 20–25% DMSO-EDTA showed little fragment length degradation when stored at 4°C for 6 hours. Samples in 95% EtOH or 20–25% DMSO-EDTA kept at 4°C for 1 week after dissection still yielded adequate amounts of uHMW DNA for most applications. Tissue type was a significant predictor of total DNA yield but not fragment length. Preservation solution had a smaller but significant influence on both fragment length and DNA yield.

Conclusion
We provide sample preservation guidelines that ensure sufficient DNA integrity and amount required for use with long-read and long-range sequencing technologies across vertebrates. Our best practices generated the uHMW DNA needed for the high-quality reference genomes for phase 1 of the Vertebrate Genomes Project, whose ultimate mission is to generate chromosome-level reference genome assemblies of all ∼70,000 extant vertebrate species.
Stardust: improving spatial transcriptomics data analysis through space-aware modularity optimization-based clustering
Authors: Avesani Simone , Viesi Eva , Alessandrì Luca , Motterle Giovanni , Bonnici Vincenzo , Beccuti Marco , Calogero Raffaele , Giugno Rosalba 
Published: August 2022

Abstract

Background
Spatial transcriptomics (ST) combines stained tissue images with spatially resolved high-throughput RNA sequencing. The spatial transcriptomic analysis includes challenging tasks like clustering, where a partition among data points (spots) is defined by means of a similarity measure. Improving clustering results is a key factor as clustering affects subsequent downstream analysis. State-of-the-art approaches group data by taking into account transcriptional similarity and some by exploiting spatial information as well. However, it is not yet clear how much the spatial information combined with transcriptomics improves the clustering result.

Results
We propose a new clustering method, Stardust, that easily exploits the combination of space and transcriptomic information in the clustering procedure through a manual or fully automatic tuning of algorithm parameters. Moreover, a parameter-free version of the method is also provided where the spatial contribution depends dynamically on the expression distances distribution in the space. We evaluated the proposed methods results by analyzing ST data sets available on the 10x Genomics website and comparing clustering performances with state-of-the-art approaches by measuring the spots' stability in the clusters and their biological coherence. Stability is defined by the tendency of each point to remain clustered with the same neighbors when perturbations are applied.

Conclusions
Stardust is an easy-to-use methodology allowing to define how much spatial information should influence clustering on different tissues and achieving more stable results than state-of-the-art approaches.
Thoracoscopic resection of pulmonary sequestration with carbon dioxide insufflation and indocyanine green
Authors: Koike Sachie , Miyazawa Masahisa , Kobayashi Nobutaka 
Published: August 2022

Abstract
We encountered a rare case of pulmonary sequestration supplied from the right renal artery, which was resected by video-assisted thoracic surgery with carbon dioxide insufflation and indocyanine green-guided technique. A 41-year-old woman with intralobar pulmonary sequestration supplied from the right renal artery was referred to our department. At the time of surgery, we used carbon dioxide insufflation to improve the manoeuvrable workspace for shutting off aberrant arteries and indocyanine green fluorescence guidance to differentiate the boundary of the sequestered lung from the normal lung. These procedures helped in the efficient resection of the lesion.
Comparison of intergenerational instrumental variable analyses of body mass index and mortality in UK Biobank
Authors: Barry Ciarrah-Jane , Carslake David , Wade Kaitlin H , Sanderson Eleanor , Davey Smith George 
Published: August 2022

Abstract

Background
An increasing proportion of people have a body mass index (BMI) classified as overweight or obese and published studies disagree whether this will be beneficial or detrimental to health. We applied and evaluated two intergenerational instrumental variable methods to estimate the average causal effect of BMI on mortality in a cohort with many deaths: the parents of UK Biobank participants.

Methods
In Cox regression models, parental BMI was instrumented by offspring BMI using an ‘offspring as instrument’ (OAI) estimation and by offspring BMI-related genetic variants in a ‘proxy-genotype Mendelian randomization’ (PGMR) estimation.

Results
Complete-case analyses were performed in parents of 233 361 UK Biobank participants with full phenotypic, genotypic and covariate data. The PGMR method suggested that higher BMI increased mortality with hazard ratios per kg/m2 of 1.02 (95% CI: 1.01, 1.04) for mothers and 1.04 (95% CI: 1.02, 1.05) for fathers. The OAI method gave considerably higher estimates, which varied according to the parent–offspring pairing between 1.08 (95% CI: 1.06, 1.10; mother–son) and 1.23 (95% CI: 1.16, 1.29; father–daughter).

Conclusion
Both methods supported a causal role of higher BMI increasing mortality, although caution is required regarding the immediate causal interpretation of these exact values. Evidence of instrument invalidity from measured covariates was limited for the OAI method and minimal for the PGMR method. The methods are complementary for interrogating the average putative causal effects because the biases are expected to differ between them.
Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker
Authors: Weigand Anne , Gärtner Matti , Scheidegger Milan , Wyss Patrik O , Henning Anke , Seifritz Erich , Stippl Anna , Herrera-Melendez Ana , Bajbouj Malek , Aust Sabine , Grimm Simone 
Published: August 2022

Abstract

Background
Growing evidence underscores the utility of ketamine as an effective and rapid-acting treatment option for major depressive disorder (MDD). However, clinical outcomes vary between patients. Predicting successful response may enable personalized treatment decisions and increase clinical efficacy.

Methods
We here explored the potential of pregenual anterior cingulate cortex (pgACC) activity to predict antidepressant effects of ketamine in relation to ketamine-induced changes in glutamatergic metabolism. Prior to a single i.v. infusion of ketamine, 24 patients with MDD underwent functional magnetic resonance imaging during an emotional picture-viewing task and magnetic resonance spectroscopy. Changes in depressive symptoms were evaluated using the Beck Depression Inventory measured 24 hours pre- and post-intervention. A subsample of 17 patients underwent a follow-up magnetic resonance spectroscopy scan.

Results
Antidepressant efficacy of ketamine was predicted by pgACC activity during emotional stimulation. In addition, pgACC activity was associated with glutamate increase 24 hours after the ketamine infusion, which was in turn related to better clinical outcome.

Conclusions
Our results add to the growing literature implicating a key role of the pgACC in mediating antidepressant effects and highlighting its potential as a multimodal neuroimaging biomarker of early treatment response to ketamine.
Expired medications and disposal practices in Arab households
Authors: Ghemrawi Rose , Kharaba Zelal , Aldulaymi Raghad , AlBataineh Nezar , Alghaly Fady , Qasem Naji , Khair Mostafa 
Published: August 2022

Abstract

Objectives
Over the past few decades, the accumulation of expired and unused medications in households has become a concern. Most people are unaware of how to properly dispose of unused and/or expired medicines. Our objective was to inspect the extent of expired medications within Arab households in United Arab Emirates (UAE), to determine which therapeutic groups yield greater amounts of unused medications, and evaluate drugs’ disposal practices.

Methods
This descriptive study was written in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for cross-sectional studies. It was conducted among Arab households in UAE (n = 503) using an online questionnaire between November 2020 and January 2021. Questions were related to participants’ socio-demographics, the prevalence of expired medications in households and their disposal.

Key findings
Around 58% of the respondents had expired medications in their houses and 74% had drugs that were never used. The most common medicines left unused were analgesics (34%) followed by cosmetics (27%) and antibiotics (26%). More than 42% of expired medications were in solid dosage forms, 28% were semisolid and 24% were liquid dosage forms. The predominant disposal method among the surveyed participants was throwing medications into the garbage (86%).

Conclusions
Large quantities of expired medications in Arab households exist with a high prevalence of analgesics, antibiotics and cosmetics. Arab households are unaware of the proper drug disposal procedures. Therefore, community pharmacists are recommended to offer training on proper medication disposal practices and to encourage the public to return medications to pharmacies.
Describing the impact of community pharmacy organisation type on emergency hormonal contraception services in England
Authors: Thayer Nick , White Simon , Frisher Martin 
Published: August 2022

Abstract

Objectives
In England, non-dispensing pharmacy services are commissioned either nationally or locally. For the national service Medicines Use Reviews (MURs), large multiple/chain pharmacies provide more consultations than independents. This study aimed to examine the relationship between community pharmacy organisation type and a local service, Emergency Hormonal Contraception (EHC). It also aimed to explore the influence of deprivation.

Methods
Freedom of information requests was sent to all 147 local authorities in England. Data included the number of EHC consultations by individual pharmacies across England (2017/18). Public data were used to identify pharmacies, match with MUR data, and group by organisation type. Bivariate correlations and ANOVA described the relationship between service provision, organisation type and deprivation.

Key findings
Pharmacy data were obtained from 76 (52%) local authorities. Following removal of unidentifiable pharmacies, 3069 were analysed – 56% of the estimated 5461 commissioned pharmacies in England. Bivariate correlations indicated a significant negative correlation between EHC provision and Index of Multiple Deprivation score. Greater deprivation correlated to greater EHC provision. A One-way ANOVA demonstrated significant differences between organisation types for MUR provision (larger organisations providing greater volumes). EHC provision demonstrated significant differences between groups and a U-shaped association; large multiple and independent organisations had higher levels than medium and small chains. A two-way ANOVA showed no significant interaction between deprivation and organisation type.

Conclusions
EHC provision does not increase linearly with organisation type. Deprivation appears a more reliable indicator of EHC provision. Provision is likely influenced by local factors but could increase with a nationally commissioned service.
Risk factors associated with cardiovascular mortality among gastric cancer patients: a population-based analysis
Authors: Wang Jing , Wang Qi , Du Xinyu , Zhu Xiaojie , Nie Chuang , Han Xu , Tian Wenjing , Li He , Zhou Haibo 
Published: August 2022

Abstract

Background
Cancer patients were found at a high risk of death from cardiovascular disease. This study aims to assess cardiovascular mortality risk and identify the potential risk factors associated with cardiovascular mortality among gastric cancer patients.

Methods
Gastric cancer patients were collected from the Surveillance Epidemiology and End Results database during 1975–2016. Standardized mortality ratios were calculated to compare cardiovascular mortality rates between gastric cancer patients and the general US population. Univariable Cox analysis and multivariable stepwise Cox analysis were adopted to identify the potential risk factors for cardiovascular disease death after gastric cancer diagnosis.

Results
There were 10 886 cardiovascular disease deaths identified among 165 433 individuals with gastric cancer observed for 410207.20 person-years. Gastric cancer patients were at a higher cardiovascular disease mortality risk (standardized mortality ratio = 3.35, 95% confidence interval: 3.24–3.47, P &lt; 0.05). The study showed that older age at diagnosis (&gt;80 years vs. 0–69 years, hazard ratio = 7.05, 95% confidence interval: 6.66–7.46, P &lt; 0.001; 70–80 years vs. 0–69 years, hazard ratio = 3.35, 95% confidence interval: 3.19–3.53, P &lt; 0.001), male sex (vs. female, hazard ratio = 1.39, 95% confidence interval: 1.33–1.45, P &lt; 0.001), black race (vs. white, hazard ratio = 1.31, 95% confidence interval: 1.24–1.38, P &lt; 0.001), without a partner (divorced/separated vs. married/partnered, hazard ratio = 1.35, 95% confidence interval: 1.25–1.45, P &lt; 0.001; single vs. married/partnered, hazard ratio = 1.20, 95% confidence interval: 1.12–1.29, P &lt; 0.001; widowed vs. married/partnered, hazard ratio = 1.41, 95% confidence interval: 1.34–1.48, P &lt; 0.001), living in the northern plains (vs. pacific coast, hazard ratio = 1.23, 95% confidence interval: 1.16–1.29, P &lt; 0.001) and surgery not performed (vs. performed, hazard ratio = 1.70, 95% confidence interval: 1.61–1.79, P &lt; 0.001) were significantly associated with increased risk of cardiovascular disease death. Compared with patients with localized stage, distant staged patients were less likely to die of cardiovascular disease (hazard ratio = 0.88, 95% confidence interval: 0.83–0.94, P &lt; 0.001).

Conclusions
Gastric cancer patients were at an increased risk of cardiovascular disease death. Older age at diagnosis, male sex, black race, without a partner, living in the northern plains and surgery not performed were significantly associated with cardiovascular disease death after gastric cancer diagnosis.
Transoral Robotic Surgery for Recurrent Tumors of the Upper Aerodigestive Tract (RECUT): An International Cohort Study
Authors: Hardman John C , Holsinger F Chris , Brady Grainne C , Beharry Avinash , Bonifer Alec T , D’Andréa Gregoire , Dabas Surender K , de Almeida John R , Duvvuri Umamaheswar , Floros Peter , Ghanem Tamer A , Gorphe Philippe , Gross Neil D , Hamilton David , Kurukulasuriya Chareeni , Larsen Mikkel Hjordt Holm , Lin Daniel J , Magnuson J Scott , Meulemans Jeroen , Miles Brett A , Moore Eric J , Pantvaidya Gouri , Roof Scott , Rubek Niclas , Simon Christian , Subash Anand , Topf Michael C , Van Abel Kathryn M , Vander Poorten Vincent , Walgama Evan S , Greenlay Emily , Potts Laura , Balaji Arun , Starmer Heather M , Stephen Sarah , Roe Justin , Harrington Kevin , Paleri Vinidh 
Published: August 2022

Abstract

Background
Transoral robotic surgery (TORS) is an emerging minimally invasive surgical treatment for residual, recurrent, and new primary head and neck cancers in previously irradiated fields, with limited evidence for its oncological effectiveness.

Methods
A retrospective observational cohort study of consecutive cases performed in 16 high-volume international centers before August 2018 was conducted (registered at clinicaltrials.gov [NCT04673929] as the RECUT study). Overall survival (OS), disease-free survival, disease-specific survivals (DSS), and local control (LC) were calculated using Kaplan-Meier estimates, with subgroups compared using log-rank tests and Cox proportional hazards modeling for multivariable analysis. Maximally selected rank statistics determined the cut point for closest surgical resection margin based on LC.

Results
Data for 278 eligible patients were analyzed, with median follow-up of 38.5 months. Two-year and 5-year outcomes were 69.0% and 62.2% for LC, 71.8% and 49.8% for OS, 47.2% and 35.7% for disease-free survival, and 78.7% and 59.1% for disease-specific survivals. The most discriminating margin cut point was 1.0 mm; the 2-year LC was 80.9% above and 54.2% below or equal to 1.0 mm. Increasing age, current smoking, primary tumor classification, and narrow surgical margins (≤1.0 mm) were statistically significantly associated with lower OS. Hemorrhage with return to theater was seen in 8.1% (n = 22 of 272), and 30-day mortality was 1.8% (n = 5 of 272). At 1 year, 10.8% (n = 21 of 195) used tracheostomies, 33.8% (n = 66 of 195) used gastrostomies, and 66.3% (n = 53 of 80) had maintained or improved normalcy of diet scores.

Conclusions
Data from international centers show TORS to treat head and neck cancers in previously irradiated fields yields favorable outcomes for LC and survival. Where feasible, TORS should be considered the preferred surgical treatment in the salvage setting.
Chronic Traumatic Encephalopathy in a Routine Neuropathology Service in Australia
Authors: Suter Catherine M , Affleck Andrew J , Lee Maggie , Davies Danielle , Burns Arran L , Sy Joanne , I’Ons Bernard , Buckland Michael E 
Published: August 2022

Abstract
Chronic traumatic encephalopathy (CTE) is a neuropathological diagnosis defined by a unique pattern of hyperphosphorylated tau (p-tau) accumulation that begins in neocortical regions of the brain. It is associated with a range of neuropsychological symptoms, but a definitive diagnosis can only be made by postmortem brain examination. In 2018, we instituted CTE screening for all autopsy brains as part of our routine departmental protocol by performing p-tau immunohistochemistry on a restricted set of 3 neocortical blocks (frontal, temporal, and parietal). This strategy allowed us to identify 4 cases of low-stage CTE from 180 consecutive autopsies. Two of the 4 cases had a documented history of brain injury; for the remaining 2 cases, there was a long history of treatment-resistant tonic/clonic epilepsy suggesting that undocumented brain injuries may have occurred. Our experience indicates that 3-block CTE screening is useful in identifying CTE in routine practice. The results of this study further support the association between prior head injuries and CTE and demonstrate that, albeit uncommon, CTE does occur in the general population. Our findings suggest that p-tau screening should be routinely pursued in brain autopsy, particularly where there is a documented or likely history of traumatic brain injury.