bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of Prevalent Versus Incident Dementia Cases in Epidemiologic Studies
Authors: Nichols Emma , Ng Derek K , James Bryan D , Deal Jennifer A , Gross Alden L 
Published: November 2022

Abstract
Because dementia is progressive, incident cases are on average milder than prevalent cases, affecting the performance of cognitive tests and questions on functional limitations (i.e., cognition/functional limitation items) used for dementia assessment. Longitudinal studies assess incident cases, while cross-sectional studies assess prevalent cases, but differences are not typically considered when researchers select items to include in studies. We used longitudinal data from the Religious Orders Study and Memory and Aging Project (ROSMAP) (n = 3,446) collected between 1994 and 2021 to characterize differences in associations between items (cognition: 35 items; functional limitations: 14 items) and incident or prevalent dementia using multinomial regression models with generalized estimating equations, controlling for ROSMAP cohort (Religious Orders Study or Memory and Aging Project), age, sex, race, and education. The association between a given item and incident dementia was significantly weaker than the association between the same item and prevalent dementia for 46 of 49 items. However, there was variability, with larger differences for some items, including naming a pencil (prevalence odds ratio = 0.02 (95% confidence interval: 0.02, 0.03); incidence odds ratio = 0.10 (95% confidence interval: 0.06, 0.17); P for difference &lt; 0.001). Important differences exist in the performance of cognition/functional limitation items for measurement of incident versus prevalent dementia. Differences can inform the choice of items for cross-sectional studies of prevalent cases or longitudinal studies of incident cases, leading to reduced misclassification and increased statistical power.
e-TSN: an interactive visual exploration platform for target–disease knowledge mapping from literature
Authors: Feng Ziyan , Shen Zihao , Li Honglin , Li Shiliang 
Published: November 2022

Abstract
Target discovery and identification processes are driven by the increasing amount of biomedical data. The vast numbers of unstructured texts of biomedical publications provide a rich source of knowledge for drug target discovery research and demand the development of specific algorithms or tools to facilitate finding disease genes and proteins. Text mining is a method that can automatically mine helpful information related to drug target discovery from massive biomedical literature. However, there is a substantial lag between biomedical publications and the subsequent abstraction of information extracted by text mining to databases. The knowledge graph is introduced to integrate heterogeneous biomedical data. Here, we describe e-TSN (Target significance and novelty explorer, http://www.lilab-ecust.cn/etsn/), a knowledge visualization web server integrating the largest database of associations between targets and diseases from the full scientific literature by constructing significance and novelty scoring methods based on bibliometric statistics. The platform aims to visualize target–disease knowledge graphs to assist in prioritizing candidate disease-related proteins. Approved drugs and associated bioactivities for each interested target are also provided to facilitate the visualization of drug–target relationships. In summary, e-TSN is a fast and customizable visualization resource for investigating and analyzing the intricate target–disease networks, which could help researchers understand the mechanisms underlying complex disease phenotypes and improve the drug discovery and development efficiency, especially for the unexpected outbreak of infectious disease pandemics like COVID-19.
Defining near-complete response following (chemo)radiotherapy for rectal cancer: systematic review
Authors: Custers Petra A , Geubels Barbara M , Beets Geerard L , Lambregts Doenja M J , van Leerdam Monique E , van Triest Baukelien , Maas Monique 
Published: November 2022

Abstract

Background
A uniform definition of a clinical near-complete response (near-CR) after neoadjuvant (chemo)radiotherapy for rectal cancer is lacking. A clear definition is necessary for uniformity in clinical practice and trial enrolment for organ-preserving treatments. This review aimed to provide an overview of the terminology, criteria, and features used in the literature to define a near-CR.

Methods
A systematic review was performed based on the PRISMA statement. PubMed and Embase were searched up to May 2021 to identify the terminology, criteria, and features used to define a near-CR after (chemo)radiotherapy for rectal cancer. Studies with no clear cut-off point between a cCR and near-CR, studies using Response Evaluation Criteria In Solid Tumours, and studies including only complete responders were excluded.

Results
A total of 1876 articles were found, of which 23 were included. Patients were managed by watchful waiting and/or additional local treatment in 11 and 17 of 23 studies respectively. Response evaluation included digital rectal examination (DRE) and/or endoscopy with MRI in 18 studies. The majority of studies used the term ‘near-complete response’. In most studies, minor irregularities or a smooth induration with DRE and a small flat ulcer on endoscopy were considered to indicate a near-CR. On MRI, five studies used features (obvious downstaging with or without heterogeneous/irregular fibrosis on T2-weighted MRI or small spot of high signal on diffusion-weighted imaging), five studies used TNM criteria (ycT2), and four used magnetic resonance tumour regression grade (mrTRG) (mrTRG1–2/mrTRG2) to describe a near-CR.

Conclusion
The terminology, criteria, and features used to describe a near-CR vary substantially, which can partly be explained by the different treatment strategies patients are selected for (watchful waiting or additional local treatment). A reproducible definition of near-CR is required.
Genome-wide contribution of common short-tandem repeats to Parkinson’s disease genetic risk
Authors: Bustos Bernabe I , Billingsley Kimberley , Blauwendraat Cornelis , Gibbs J Raphael , Gan-Or Ziv , Krainc Dimitri , Singleton Andrew B , Lubbe Steven J ,   International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: November 2022

Abstract
Parkinson’s disease is a complex neurodegenerative disorder with a strong genetic component, for which most known disease-associated variants are single nucleotide polymorphisms (SNPs) and small insertions and deletions (indels). DNA repetitive elements account for &gt;50% of the human genome; however, little is known of their contribution to Parkinson’s disease aetiology. While select short tandem repeats (STRs) within candidate genes have been studied in Parkinson’s disease, their genome-wide contribution remains unknown. Here we present the first genome-wide association study of STRs in Parkinson’s disease. Through a meta-analysis of 16 imputed genome-wide association study cohorts from the International Parkinson’s Disease Genomic Consortium (IPDGC), totalling 39 087 individuals (16 642 cases and 22 445 controls of European ancestry), we identified 34 genome-wide significant STR loci (P &lt; 5.34 × 10−6), with the strongest signal located in KANSL1 [chr17:44 205 351:[T]11, P = 3 × 10−39, odds ratio = 1.31 (95% confidence interval = 1.26–1.36)]. Conditional-joint analyses suggested that four significant STRs mapping nearby NDUFAF2, TRIML2, MIRNA-129–1 and NCOR1 were independent from known risk SNPs. Including STRs in heritability estimates increased the variance explained by SNPs alone. Gene expression analysis of STRs (eSTRs) in RNA sequencing data from 13 brain regions identified significant associations of STRs influencing the expression of multiple genes, including known Parkinson’s disease genes. Further functional annotation of candidate STRs revealed that significant eSTRs within NUDFAF2 and ZSWIM7 overlap with regulatory features and are associated with change in the expression levels of nearby genes. Here, we show that STRs at known and novel candidate loci contribute to Parkinson’s disease risk and have functional effects in disease-relevant tissues and pathways, supporting previously reported disease-associated genes and giving further evidence for their functional prioritization. These data represent a valuable resource for researchers currently dissecting Parkinson’s disease risk loci.
Transthyretin attenuates TDP-43 proteinopathy by autophagy activation via ATF4 in FTLD-TDP
Authors: Chu Yuan-Ping , Jin Lee-Way , Wang Liang-Chao , Ho Pei-Chuan , Wei Wei-Yen , Tsai Kuen-Jer 
Published: November 2022

Abstract
TAR DNA-binding protein-43 (TDP-43) proteinopathies are accompanied by the pathological hallmark of cytoplasmic inclusions in the neurodegenerative diseases, including frontal temporal lobar degeneration-TDP and amyotrophic lateral sclerosis. We found that transthyretin accumulates with TDP-43 cytoplasmic inclusions in frontal temporal lobar degeneration-TDP human patients and transgenic mice, in which transthyretin exhibits dramatic expression decline in elderly mice. The upregulation of transthyretin expression was demonstrated to facilitate the clearance of cytoplasmic TDP-43 inclusions through autophagy, in which transthyretin induces autophagy upregulation via ATF4. Of interest, transthyretin upregulated ATF4 expression and promoted ATF4 nuclear import, presenting physical interaction. Neuronal expression of transthyretin in frontal temporal lobar degeneration-TDP mice restored autophagy function and facilitated early soluble TDP-43 aggregates for autophagosome targeting, ameliorating neuropathology and behavioural deficits. Thus, transthyretin conducted two-way regulations by either inducing autophagy activation or escorting TDP-43 aggregates targeted autophagosomes, suggesting that transthyretin is a potential modulator therapy for neurological disorders caused by TDP-43 proteinopathy.
Maternal Antibody Response and Transplacental Transfer Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection or Vaccination in Pregnancy
Authors: Otero Sebastian , Miller Emily S , Sunderraj Ashwin , Shanes Elisheva D , Sakowicz Allie , Goldstein Jeffery A , Mithal Leena B 
Published: November 2022

AbstractBackgroundPregnant persons are at increased risk of severe coronavirus disease 2019 (COVID-19) and adverse obstetric outcomes. Understanding maternal antibody response, duration, and transplacental transfer after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccination is important to inform public health recommendations.MethodsThis prospective observational cohort study included 351 pregnant people who had SARS-CoV-2 infection or COVID-19 vaccination during pregnancy. Immunoglobulin (Ig) G and IgM to SARS-CoV-2 S1 receptor binding domain were measured in maternal and cord blood. Antibody levels and transplacental transfer ratios were compared across (1) disease severity for those with SARS-CoV-2 infection and (2) infection versus vaccination.ResultsThere were 252 individuals with SARS-CoV-2 infection and 99 who received COVID-19 vaccination during pregnancy. Birthing people with more severe SARS-CoV-2 infection had higher maternal and cord blood IgG levels (P = .0001, P = .0001). Median IgG transfer ratio was 0.87–1.2. Maternal and cord blood IgG were higher after vaccination than infection (P = .001, P = .001). Transfer ratio was higher after 90 days in the vaccinated group (P &lt; .001). Modeling showed higher amplitude and half-life of maternal IgG following vaccination (P &lt; .0001). There were no significant differences by fetal sex.ConclusionsCOVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG levels, higher cord blood IgG, and higher transfer ratio after 90 days compared with SARS-CoV-2 infection. Greater infection severity leads to higher maternal and cord blood antibodies. Maternal IgG decreases over time following both vaccination and infection, reinforcing the importance of vaccination, even after infection, and vaccine boosters for pregnant patients.
Omicron Subvariants: Clinical, Laboratory, and Cell Culture Characterization
Authors: Morris C Paul , Eldesouki Raghda E , Sachithanandham Jaiprasath , Fall Amary , Norton Julie M , Abdullah Omar , Gallagher Nicholas , Li Maggie , Pekosz Andrew , Klein Eili Y , Mostafa Heba H 
Published: November 2022

AbstractBackgroundThe variant of concern Omicron has become the sole circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant for the past several months. Omicron subvariants BA.1, BA.2, BA.3, BA.4, and BA.5 evolved over the time, with BA.1 causing the largest wave of infections globally in December 2021–January 2022. This study compared the clinical outcomes in patients infected with different Omicron subvariants and the relative viral loads and recovery of infectious virus from upper respiratory specimens.MethodsSARS-CoV-2–positive remnant clinical specimens, diagnosed at the Johns Hopkins Microbiology Laboratory between December 2021 and July 2022, were used for whole-genome sequencing. The clinical outcomes of infections with Omicron subvariants were compared with infections with BA.1. Cycle threshold (Ct) values and the recovery of infectious virus on the VeroTMPRSS2 cell line from clinical specimens were compared.ResultsBA.1 was associated with the largest increase in SARS-CoV-2 positivity rate and coronavirus disease 2019 (COVID-19)–related hospitalizations at the Johns Hopkins system. After a peak in January, cases decreased in the spring, but the emergence of BA.2.12.1 followed by BA.5 in May 2022 led to an increase in case positivity and admissions. BA.1 infections had a lower mean Ct value when compared with other Omicron subvariants. BA.5 samples had a greater likelihood of having infectious virus at Ct values &lt;20.ConclusionsOmicron subvariants continue to be associated with a relatively high rate of polymerase chain reaction (PCR) positivity and hospital admissions. The BA.5 infections are more while BA.2 infections are less likely to have infectious virus, suggesting potential differences in infectibility during the Omicron waves.
Implementation of a method for sperm cryopreservation in sceloporine lizards
Authors: Sánchez-Rivera Uriel Á , Medrano Alfredo , Cruz-Cano Norma B , Alcántar-Rodríguez Alicia , Dávila-Govantes Rodrigo , Castro-Camacho Yabín J , Martínez-Torres Martín 
Published: November 2022

Abstract
Actual loss of lizard biodiversity continues, even with the implementation of conventional conservation programs. An approach including assisted reproductive techniques such as sperm cryopreservation may contribute to the management of endangered species. We developed a method for sperm cryopreservation in sceloporine lizards and compared the response among the studied species. Prior to the mating season, we obtained semen from adult males of Sceloporus aeneus (n = 21), Sceloporus grammicus (n = 20) and Sceloporus torquatus (n = 21) via pressure of the genital papilla. Volume and sperm concentration were measured before semen dilution in a Tris–egg yolk (TEY) medium to evaluate progressive motility, sperm viability, morphology, plasma membrane and acrosome integrity. Then, we cooled the remaining volumes to 5°C at a rate of 0.1°C per minute to incorporate glycerol (8% v/v) in two fractions. Immediately afterwards, we placed 40 μl of the mix on solid CO2 to form pellets and immersed them in liquid nitrogen for storage. We thawed the pellets at 29°C for 3 minutes and diluted them 1:1 (v/v) in TEY medium to assess sperm quality. We found a positive relationship between body weight and seminal volume in S. grammicus and S. torquatus and a negative correlation with sperm concentration in S. grammicus (P &lt; 0.05). Moreover, we observed that the freezing–thawing process decreased sperm quality in the three species, mostly affecting motility and viability. However, S. torquatus and S. aeneus showed a higher sperm tolerance than S. grammicus.
Combined atrial fibrillation ablation and left atrial appendage occlusion procedure in the United States: a propensity score matched analysis from 2016–2019 national readmission database
Authors: Pasupula Deepak Kumar , Siddappa Malleshappa Sudeep K , Munir Muhammad B , Bhat Anusha Ganapati , Anandaraj Antony , Jakkoju Avaneesh , Spooner Michael , Koranne Ketan , Hsu Jonathan C , Olshansky Brian , Camm A John 
Published: November 2022

AbstractAimsThe safety and feasibility of combining percutaneous catheter ablation (CA) for atrial fibrillation with left atrial appendage occlusion (LAAO) as a single procedure in the USA have not been investigated. We analyzed the US National Readmission Database (NRD) to investigate the incidence of combined LAAO + CA and compare major adverse cardiovascular events (MACEs) with matched LAAO-only and CA-only patients.Methods and resultsIn this retrospective study from NRD data, we identified patients undergoing combined LAAO and CA procedures on the same day in the USA from 2016 to 2019. A 1:1 propensity score match was performed to identify patients undergoing LAAO-only and CA-only procedures. The number of LAAO + CA procedures increased from 28 (2016) to 119 (2019). LAAO + CA patients (n = 375, mean age 74 ± 9.2 years, 53.4% were males) had non-significant higher MACE (8.1%) when compared with LAAO-only (n = 407, 5.3%) or CA-only patients (n = 406, 7.4%), which was primarily driven by higher rate of pericardial effusion (4.3%). All-cause 30-day readmission rates among LAAO + CA patients (10.7%) were similar when compared with LAAO-only (12.7%) or CA-only (17.5%) patients. The most frequent primary reason for readmissions among LAAO + CA and LAAO-only cohorts was heart failure (24.6 and 31.5%, respectively), while among the CA-only cohort, it was paroxysmal atrial fibrillation (25.7%).ConclusionWe report an 63% annual growth (from 28 procedures) in combined LAAO and CA procedures in the USA. There were no significant difference in MACE and all-cause 30-day readmission rates among LAAO + CA patients compared with matched LAAO-only or CA-only patients.
Atrial fibrillation onset before heart failure or vice versa: what is worst? A nationwide register study
Authors: Pallisgaard Jannik , Greve Anders M , Lock-Hansen Morten , Thune Jens Jakob , Fosboel Emil Loldrup , Devereux Richard B , Okin Peter M , Gislason Gunnar H , Torp-Pedersen Christian , Bang Casper N 
Published: November 2022

AbstractAimsAtrial fibrillation (AF) and heart failure (HF) often coexist. However, whether AF onset before HF or vice versa is associated with the worst outcome remains unclear. A consensus of large studies can guide future research and preventive strategies to better target high-risk patients.Methods and resultsWe included all Danish cases with the coexistence of AF and HF (2005–17) using nationwide registries. Patients were divided into three separate groups (i) AF before HF, (ii) HF before AF, or (iii) AF and HF diagnosed concurrently (±30 days). Adjusting landmark Cox analyses (index date was the time of the latter diagnosis of AF or HF) were used for evaluating the association of the three groups with a composite outcome of ischaemic stroke or death. Among a total of 49 042 patients included, 40% had AF before HF, 27% had HF before AF, and 33% had AF and HF diagnosed concurrently. The composite endpoint accrued more often in patients with HF before AF compared to the two other groups (&lt;0.001), and this remained significant in the adjusted analyses with hazard ratios (95% confidence intervals) of 1.26 (1.22–1.30) compared to AF before HF. Finally, antihypertensive treatment, oral anticoagulants, amiodarone, statins, and AF ablation were associated with a lower hazard ratio of the composite endpoint (all &lt; 0.001).ConclusionsIn this large Danish national cohort, diagnosis of HF before AF was associated with an increased absolute risk of death compared to AF before HF and AF and HF diagnosed concurrently. Antihypertensive treatment, oral anticoagulants, amiodarone, statins, and AF ablation may improve prognosis.
Quantitative assessment of transmural fibrosis profile in the human atrium: evidence for a three-dimensional arrhythmic substrate by slice-to-slice histology
Authors: Ravelli Flavia , Masè Michela , Cristoforetti Alessandro , Avogaro Laura , D’Amato Elvira , Tessarolo Francesco , Piccoli Federico , Graffigna Angelo 
Published: November 2022

AbstractAimsIntramural fibrosis represents a crucial factor in the formation of a three-dimensional (3D) substrate for atrial fibrillation (AF). However, the transmural distribution of fibrosis and its relationship with atrial overload remain largely unknown. The aim of this study is to quantify the transmural profile of atrial fibrosis in patients with different degrees of atrial dilatation and arrhythmic profiles by a high-resolution 3D histology method.Methods and resultsSerial microtome-cut tissue slices, sampling the entire atrial wall thickness at 5 µm spatial resolution, were obtained from right atrial appendage specimens in 23 cardiac surgery patients. Atrial slices were picrosirius red stained, imaged by polarized light microscopy, and analysed by a custom-made segmentation algorithm. In all patients, the intramural fibrosis content displayed a progressive decrease alongside tissue depth, passing from 68.6 ± 11.6% in the subepicardium to 10–13% in the subendocardium. Distinct transmural fibrotic profiles were observed in patients with atrial dilatation with respect to control patients, where the first showed a slower decrease of fibrosis along tissue depth (exponential decay constant: 171.2 ± 54.5 vs. 80.9 ± 24.4 µm, P &lt; 0.005). Similar slow fibrotic profiles were observed in patients with AF (142.8 ± 41.7 µm). Subepicardial and midwall levels of fibrosis correlated with the degree of atrial dilatation (ρ = 0.72, P &lt; 0.001), while no correlation was found in subendocardial layers.ConclusionsQuantification of fibrosis transmural profile at high resolution is feasible by slice-to-slice histology. Deeper penetration of fibrosis in subepicardial and midwall layers in dilated atria may concur to the formation of a 3D arrhythmic substrate.
The bacteriome of the halophyte Atriplex nummularia (old man saltbush) in salt-affected soils - an ecological model
Authors: Alfradique Monteiro Douglas , Fazolato Carolline Silva Barbosa , Martins Luiz Fernando , Tavora Coelho da Costa Rachid Caio 
Published: November 2022

Abstract
Halophytes, plants capable of growing under saline conditions, are an important source of bacteria with biotechnological potential for plant growth under extreme conditions. In this study, we evaluated the halophyte Atriplex nummularia bacteriome assemblage from three different salinized sites in northeastern Brazil with different edaphoclimatic characteristics, understanding the participation of the plant in the assembly of its microbiome. We sampled 30 specimens, from which the leaves, roots, and rhizospheric soil were subjected to 16S rRNA gene sequencing, bringing forth patterns of alpha and beta diversity, taxonomical composition, co-occurrence network, and the core microbiome of each compartment. Overall, this species harbors a very restricted set of endophytic microbes, and communities showed an increasing gradient of complexity (soil &gt; root &gt; leaf), reflecting a change in the main selective pressure being active over the microbial community. Although the leaf bacteriome was influenced basically by host factors, the soil community was modulated by the environment, and the root bacteriome was structured by both factors. These results help us understand how plant–microbe interactions occur in saline environments. As these plants shelter microbes that potentially alleviate abiotic stresses, we discuss how culture-independent methods could contribute to the prospection of plant growth promoting bacteria in plants.