bluuebunny/crossref_metadata_2025 huggingface dataset:
B-375 Mer-idpcr: A Method for Sequence-specific Measurement of Small RNA Expression and Methylation in Liquid Biopsies
Authors: Horos R , Daniel-Moreno A , Bieg-Salazar C , Skottke J , Ceiler J , Sanchez-Delgado M , Sikosek T , Rajakumar T , Steinkraus B R
Published: September 2023

Background

Small RNAs are an important class of biomarkers in liquid biopsy for cancer diagnostics. New discoveries in the field of “epitranscriptomics” have uncovered further functional layers of tumor biology that are ignored by standard gene expression measurement methods. Therefore, there is a pressing need for sequence specific methods that can detect methylation stoichiometry on small RNAs purified from liquid biopsies in a diagnostic setting.

Methods

To detect small RNAs specifically, we designed structured oligonucleotide adapters that bear reverse complementary overhangs to both the 5′ and 3′ end of target RNAs. After nick-based ligation, reverse transcription under limiting dNTP conditions enables the differential processing of methylated vs unmethylated species. Finally, target specific TaqMan probes are used on a digital PCR based platform for final quantification and calculation of methylation stoichiometry.

Results

We show that mer-idPCR can detect target RNAs in a sequence-specific manner using synthetic cognate RNA oligos and specificity controls, such as nucleotide variants or non-target miRNAs. Detected RNA is quantified in a linear range with a limit of detection at 40 copies/µL of cDNA. Concurrently, the method can detect 2′-o-methylation in 0%–100% range with a resolution of 10%. mer-idPCR can be applied to RNA extracted from various sources including serum, plasma or whole blood stabilizing tubes.

Conclusion

mer-idPCR can enable the high resolution, sequence specific quantification of target small RNA species, in addition to the measurement of 2′-o-methylation site status, in small RNAs extracted from peripheral blood. We show the adapter design requirements and discuss optimizations of adapter design and reverse transcription conditions that led to improved specificity, reproducibility, and linearity of this method. mer-idPCR enables the validation and discovery of novel biomarkers for cancer detection in liquid biopsies.
B-378 Cell-free Plasma Preparation Workflow Solution
Authors: Manley L , Lopez S , Kothandaramaswamy L , Saunders H , Cheng A
Published: September 2023

Background

Liquid biopsy for the study and monitoring of various cancers has become a growing area of study, pre-analytical sample handling can impact the quality and profile of the circulating tumor nucleic acid. Preparing samples like cell-free plasma for downstream assays is imperative to maintaining quality in downstream applications for clinical research in oncology. To obtain cell-free plasma, blood samples must undergo centrifugation at 2000g for 10 min at 4C followed by a second spin for 30 min at 4C. This two-step spin process presents an issue with labs that don’t have a refrigerated centrifuge suitable for higher speeds.

Methods

Here, we perform a series of studies to investigate the impact of various spin conditions on cell-free nucleic acid recovery and quality. Four plasma centrifugation methods encompassing variables attributing to speed, temperature, and number of centrifugations steps, were evaluated from whole blood tubes obtained from six donors in K2EDTA upfront of nucleic acid isolation with MagMAX™ cell-free TNA nucleic acid isolation chemistry on a KingFisher™ magnetic particle processor. Yield, quality, and functional performance was evaluated from the extracted cell-free nucleic acid and compared across all plasma spin-down methods.

Result

Study results indicated that centrifugation of plasma at lower speeds for a shorter period at room temperature had no negative impact to nucleic acid recovery and integrity.

Conclusion

Here, we offer a plasma spin workflow solution to mid- to high- throughput clinical research labs to allow versatility within the laboratory setup. Reducing the need for refrigerated centrifugation allows clinical researchers to obtain high-quality cfNA suitable for their downstream applications in clinical oncology and genomics research.
Percutaneous closure of ‘complex’ multi-fenestrated atrial septal aneurysm in visceral situs inversus using a multi-device approach: a case report
Authors: Scalera Silvia , Pizzuto Alessandra , Marchese Pietro , Santoro Giuseppe
Published: September 2023

Background

Percutaneous closure is nowadays still deemed challenging in patent forame ovale (PFO) associated to multi-fenestrated atrial septal aneurysm (ASA). This anatomic arrangement is still considered a significant risk factor for recurrence of paradoxical embolism. Theoretically, transcatheter approach could be theoretically even more complex in the case of dextrocardia and visceral situs inversus.

Case summary

A 59-year-old man with history of migraine with aura and multiple cryptogenic strokes was referred for percutaneous closure of a PFO with associated ASA. He had been previously submitted to repeat attempt of percutaneous closure with not self-centering and self-centering devices that failed due to unfavorable anatomic characteristics (dextrocardia with situs viscerum inversus, huge ASA, multiple fenestrations, large PFO). Based on this “complex” anatomy, a sequential 2-step interventional approach aiming to reduce size and mobility of the atrial septal aneurysm with a suture-based approach (Noblestich™ EL, HeartStitch, Fountain Valley, CA, USA) and to close any eventual accessory fenestrations with a not self-centering occluding device was planned. At the end of the procedure, the ASA completely disappeared and no residual shunt was imaged at TEE bubble test.

Discussion

We describe a very rare case of symptomatic ASA-PFO in dextrocardia with situs viscerum inversus as well as an innovative approach to treat such complex anatomic setting by using the suture-based closure of a PFO to reduce size and mobility of an ASA in order to deploy dedicated not-self-centering occluding devices.
Magnetic resonance detection of advanced atrial cardiomyopathy increases the risk for atypical atrial flutter occurrence following atrial fibrillation ablation
Authors: Ferró Elisenda , Pérez Núria , Althoff Till , Guasch Eduard , Prat Susana , Doltra Adelina , Borrás Roger , Tolosana José María , Arbelo Elena , Sitges Marta , Porta-Sánchez Andreu , Roca-Luque Ivo , Mont Lluís , Guichard Jean-Baptiste
Published: September 2023

Aims

Recurrence of arrhythmia after catheter ablation of atrial fibrillation (AF) in the form of atypical atrial flutter (AFL) is common among a significant number of patients and often requires redo ablation with limited success rates. Identifying patients at high risk of AFL after AF ablation could aid in patient selection and personalized ablation approach. The study aims to assess the relationship between pre-existing atrial cardiomyopathy and the occurrence of AFL following AF ablation.

Methods and results

We analysed a cohort of 1007 consecutive AF patients who underwent catheter ablation and were included in a prospective registry. Patients who did not have baseline cardiac magnetic resonance imaging and late gadolinium enhancement (LGE-CMR) or did not experience any recurrences were excluded. A total of 166 patients were included gathering 56 patients who underwent re-ablation due to AFL recurrences and 110 patients who underwent re-ablation due to AF recurrences (P = 0.11). A multiparametric assessment of atrial cardiomyopathy was based on basal LGE-CMR, including left atrial (LA) volume, LA sphericity, and global and segmental LA fibrosis using semiautomated post-processing software. Out of the initial cohort of 1007 patients, AFL and AF occurred in 56 and 110 patients, respectively. An age higher than 65 [odds ratio (OR) = 5.6, 95% confidence interval (CI): 2.2–14.4], the number of previous ablations (OR = 3.0, 95% CI: 1.2–7.8), and the management of ablation lines in the index procedure (OR = 2.5, 95% CI: 1.0–6.3) were independently associated with AFL occurrence. Furthermore, several characteristics assessed by LGE-CMR were identified as independent predictors of AFL recurrence after the index ablation for AF, such as enhanced LA sphericity (OR = 1.3, 95% CI: 1.1–1.6), LA global fibrosis (OR = 1.03, 95% CI: 1.01–1.07), and increased fibrosis in the lateral wall (OR = 1.03, 95% CI: 1.01–1.04).

Conclusion

Advanced atrial cardiomyopathy assessed by LGE-CMR, such as increased LA sphericity, global LA fibrosis, and fibrosis in the lateral wall, is independently associated with arrhythmia recurrence in the form of AFL following AF ablation.
Is use of a long-term proton pump inhibitor or histamine-2 receptor antagonist a risk factor for iron-deficiency anaemia in Taiwan? A neglected clinical drug-drug interaction
Authors: Wu Yi-Ting , Lu Ya-Ting , Chu Chao-Yu , Chao Horng-Jiun , Kuo Li-Na , Cheng Kuei-Ju , Chen Hsiang-Yin
Published: September 2023

Background

Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists change the gastric pH and reduce the intestinal absorption of nonheme iron. Case reports and case-control studies have demonstrated that absorption of iron is affected by gastric acidity, but the clinical importance of these drug-drug interactions has remained uncertain.

Objectives

The present case-control study employed 2 million longitudinal claims in 2011–2018 in the Taiwan National Health Insurance Research Database to investigate the impact of PPIs/H2 antagonists on the occurrence of iron-deficiency anaemia (IDA).

Methods

The present study retrospectively compared exposure to PPIs/H2 antagonists for 1 year among 5,326 cases with IDA and 21,304 matched controls. The postdiagnosis prescribing pattern was also calculated to understand current practice.

Results

Long-term (≥2 month) use of PPIs/H2 antagonists resulted in a higher risk of developing IDA than noncontinuous use/nonuse of those drugs (adjusted odds ratio [aOR] = 2.36, 95% confidence interval [CI] = 1.94–2.86, P < 0.001). There were significant changes in the postdiagnosis prescribing patterns of PPIs/H2 antagonists. The risk of developing IDA remained significant in the female subgroup (aOR = 2.16, 95% CI = 1.73–2.70, P < 0.001) and was even more prominent in those aged ≥ 50 years (aOR = 2.68, 95% CI = 1.94–3.70, P < 0.05).

Conclusions

This study found that long-term use of PPIs/H2 antagonists increased the risk of developing IDA, and there was strong evidence of prescription pattern adjustments postdiagnosis. Physicians and pharmacists should be aware of this risk when patients are expected to take or have been taking PPIs/H2 antagonists for the long term.
Assessing large-scale mantle compositional heterogeneity from machine learning analysis of 28 global P- and S-wave tomography models
Authors: Rahimzadeh Bajgiran Moloud , Colli Lorenzo , Wu Jonny
Published: September 2023

Differences between P- and S-wave models have been frequently used as evidence for the presence of large-scale compositional heterogeneity in the Earth's mantle. Our two-step machine learning (ML) analysis of 28 P- and S-wave global tomographic models reveals that, on a global scale, such differences are for the most part not intrinsic and could be reduced by changing the models in their respective null spaces. In other words, P- and S-wave images of mantle structure are not necessarily distinct from each other. Thus, a purely thermal explanation for large-scale seismic structure is sufficient at present; significant mantle compositional heterogeneities do not need to be invoked. We analyse 28 widely used tomographic models based on various theoretical approximations ranging from ray theory (e.g. UU-P07 and MIT-P08), Born scattering (e.g. DETOX) and full-waveform techniques (e.g. CSEM and GLAD). We apply Varimax principal component analysis to reduce tomography model dimensionality by 83 percent, while preserving relevant information (94 percent of the original variance), followed by hierarchical clustering (HC) analysis using Ward's method to quantitatively categorize all models into hierarchical groups based on similarities. We found two main tomography model clusters: Cluster 1, which we called ‘Pure P wave’, is composed of six P-wave models that only use longitudinal body wave phases (e.g. P, PP and Pdiff); and Cluster 2, which we called ‘Mixed’, includes both P- and S-wave models. P-wave models in the ‘Mixed’ cluster use inversion methods that include inputs from other geophysical and geological data sources, and this causes them to be more similar to S-wave models than Pure P-wave models without significant loss of fitness to P-wave data. Given that inclusion of new data classes and seismic phases in more recent tomographic models significantly changes imaged seismic structure, our ML assessment of global tomography model similarity may improve selection of appropriate P- and S-wave models for future global tomography comparative studies.
Prevalence of parental supply of alcohol to minors: a systematic review
Authors: van der Kruk Shannen , Harrison Nathan J , Bartram Ashlea , Newton Skye , Miller Caroline , Room Robin , Olver Ian , Bowden Jacqueline
Published: September 2023

Parental supply of alcohol to minors (i.e. those under the legal drinking age) is often perceived by parents as protective against harms from drinking, despite evidence linking it with adverse alcohol-related outcomes. This systematic review describes the prevalence of parental supply of alcohol, as reported in the international literature. The review was registered with PROSPERO (CRD42020218754). We searched seven online databases (Medline, Embase, PsycINFO, CINAHL, Scopus, Web of Science and Public Health Database) and grey literature from January 2011 to December 2022 and assessed the risk of bias with the JBI Critical Appraisal Checklist. Among 58 articles included in narrative synthesis from 29 unique datasets, there was substantial variation in the definition and measurement of parental supply of alcohol. Overall prevalence rates ranged from 7.0 to 60.0% for minor-report samples, and from 24.0 to 48.0% for parent-report samples. Data indicate that parental supply prevalence is generally proportionately higher for older minors or later-stage students, for girls, and has increased over time among minors who report drinking. Literature on the prevalence of parental supply of alcohol is robust in quantity but inconsistent in quality and reported prevalence. Greater consistency in defining and measuring parental supply is needed to better inform health promotion initiatives aimed at increasing parents’ awareness.
Spatiotemporal miRNA and transcriptomic network dynamically regulate the developmental and senescence processes of poplar leaves
Authors: Du Kang , Jiang Shenxiu , Chen Hao , Xia Yufei , Guo Ruihua , Ling Aoyu , Liao Ting , Wu Wenqi , Kang Xiangyang
Published: September 2023

Poplar is an important afforestation and urban greening species. Poplar leaf development occurs in stages, from young to mature and then from mature to senescent; these are accompanied by various phenotypic and physiological changes. However, the associated transcriptional regulatory network is relatively unexplored. We first used principal component analysis to classify poplar leaves at different leaf positions into two stages: developmental maturity (the stage of maximum photosynthetic capacity); and the stage when photosynthetic capacity started to decline and gradually changed to senescence. The two stages were then further subdivided into five intervals by gene expression clustering analysis: young leaves, the period of cell genesis and functional differentiation (L1); young leaves, the period of development and initial formation of photosynthetic capacity (L3–L7); the period of maximum photosynthetic capacity of functional leaves (L9–L13); the period of decreasing photosynthetic capacity of functional leaves (L15–L27); and the period of senescent leaves (L29). Using a weighted co-expression gene network analysis of regulatory genes, high-resolution spatiotemporal transcriptional regulatory networks were constructed to reveal the core regulators that regulate leaf development. Spatiotemporal transcriptome data of poplar leaves revealed dynamic changes in genes and miRNAs during leaf development and identified several core regulators of leaf development, such as GRF5 and MYB5. This in-depth analysis of transcriptional regulation during leaf development provides a theoretical basis for exploring the biological basis of the transcriptional regulation of leaf development and the molecular design of breeding for delaying leaf senescence.
Development and validation of a bioanalytical assay for the measurement of total and unbound teicoplanin in human serum
Authors: Mouton J W A , Raaijmakers J , Botterblom M , Toonen M , ter Heine R , Smeets R L , Brüggemann R J M , te Brake L , Jager N G L
Published: September 2023

Background

The glycopeptide teicoplanin is considered first-line treatment for severe infections caused by Gram-positive bacteria. Individualized treatment of teicoplanin is gaining interest. As only protein-unbound drug is pharmacologically active, a sensitive assay measuring unbound and total teicoplanin is indispensable for pharmacological research and dose optimization.

Objectives

To develop and validate a UPLC-MS/MS method to quantify unbound and total teicoplanin in human serum.

Methods

The developed assay was validated according to the ICH guideline M10 on Bioanalytical Method Validation and study sample analysis. Unbound teicoplanin was obtained by ultrafiltration. The assay was cross-validated with a quantitative microsphere (QMS) immunoassay in a side-by-side comparison using 40 patient samples.

Results

With the developed and validated method, all main teicoplanin components (A2-1, A2-2/A2-3, A2-4/A2-5 and A3-1) can be quantified. Total run time was 5.5 min. Concentration range was 2.5–150 mg/L for total and 0.1–25 mg/L for unbound teicoplanin. Precision (coefficient of variation) and accuracy (bias) of total teicoplanin were 5.97% and 107%, respectively, and 7.17% and 108%, respectively, for unbound teicoplanin.

Bland–Altman analysis showed total concentrations measured with the UPLC-MS/MS method were equivalent to the results of the QMS immunoassay. A total of 188 samples from 30 patients admitted to the ICU and haematology department were measured; total concentrations ranged between 2.92 and 98.5 mg/L, and unbound concentrations ranged between 0.37 and 30.7 mg/L.

Conclusions

The developed method provided rapid, precise and accurate measurement of unbound and total teicoplanin. The developed method is now routinely applied in pharmacological research and clinical practice.
Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair
Authors: Estep Katrina N , Tobias John W , Fernandez Rafael J , Beveridge Brinley M , Johnson F Brad
Published: September 2023

Although mechanisms of telomere protection are well-defined in differentiated cells, how stem cells sense and respond to telomere dysfunction, in particular telomeric double-strand breaks (DSBs), is poorly characterized. Here, we report the DNA damage signaling, cell cycle, and transcriptome changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineer human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response, which leads to p53-independent cell cycle arrest in G2. Using CRISPR–Cas9 to cripple the catalytic domain of telomerase reverse transcriptase, we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres, which instead are effectively repaired by robust homologous recombination (HR). In contrast to HR-based telomere maintenance in mouse embryonic stem cells, where HR causes ZSCAN4-dependent extension of telomeres beyond their initial lengths, HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length, which is compatible with sustained survival of the cells over several days of TRF1-FokI induction. Our findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DNA damage.
Comparison of the Standard E TB-Feron ELISA and QuantiFERON-TB Gold PLUS assays: the advantageous use of whole recombinant protein antigens for latent tuberculosis diagnosis
Authors: Lee Da-Gyum , Kang Jihye , Jung Jihee , Kim Taeyoon , Kim Jiyeon , Lee Hyunjin , Lee Junghee , Won Youngsub , Ryoo Sungweon
Published: September 2023

The laboratory diagnosis of latent tuberculosis is often performed using interferon-gamma release assays. Here, we compared two enzyme-linked immunosorbent assay-based interferon-gamma release assays, namely, the newly developed Standard E TB-Feron enzyme-linked immunosorbent assay (STFE) and the QuantiFERON-TB Gold PLUS assay (QFT-GP), using samples from 155 participants. The STFE is based on using whole EAST6 and CFP10 recombinant antigens for latent tuberculosis diagnosis. The participants were classified into four groups and screened using both assays per the manufacturers’ instructions. Thereafter, two statistical analyses were conducted to compare the obtained results. First, the STFE results were compared with the QTF-GP results (used as the gold standard) to calculate the total concordance, sensitivity, and specificity of STFE. Second, positivity and negativity concordances were calculated to differentiate healthy participants from participants with tuberculosis. The STFE showed 97% and 94% sensitivity and specificity, respectively. Furthermore, its positivity and negativity concordances were 91% and 98%, respectively. These results indicate the coordinated clinical performance of STFE in detecting latent tuberculosis and its improved performance in targeting tuberculosis-infected participants. Based on the comparison of the latent tuberculosis diagnostic abilities of STFE and QFT-GP, we establish the suitability and superior performance of STFE as a diagnostic tool.
A biomarker framework for cardiac aging: the Aging Biomarker Consortium consensus statement
Authors:   Aging Biomarker Consortium, Zhang Weiwei , Che Yang , Tang Xiaoqiang , Chen Siqi , Song Moshi , Wang Li , Sun Ai-Jun , Chen Hou-Zao , Xu Ming , Wang Miao , Pu Jun , Li Zijian , Xiao Junjie , Cao Chun-Mei , Zhang Yan , Lu Yao , Zhao Yingxin , Wang Yan-Jiang , Zhang Cuntai , Shen Tao , Zhang Weiqi , Tao Ling , Qu Jing , Tang Yi-Da , Liu Guang-Hui , Pei Gang , Li Jian , Cao Feng
Published: September 2023

Cardiac aging constitutes a significant risk factor for cardiovascular diseases prevalent among the elderly population. Urgent attention is required to prioritize preventive and management strategies for age-related cardiovascular conditions to safeguard the well-being of elderly individuals. In response to this critical challenge, the Aging Biomarker Consortium (ABC) of China has formulated an expert consensus on cardiac aging biomarkers. This consensus draws upon the latest scientific literature and clinical expertise to provide a comprehensive assessment of biomarkers associated with cardiac aging. Furthermore, it presents a standardized methodology for characterizing biomarkers across three dimensions: functional, structural, and humoral. The functional dimension encompasses a broad spectrum of markers that reflect diastolic and systolic functions, sinus node pacing, neuroendocrine secretion, coronary microcirculation, and cardiac metabolism. The structural domain emphasizes imaging markers relevant to concentric cardiac remodeling, coronary artery calcification, and epicardial fat deposition. The humoral aspect underscores various systemic (N) and heart-specific (X) markers, including endocrine hormones, cytokines, and other plasma metabolites. The ABC’s primary objective is to establish a robust foundation for assessing cardiac aging, thereby furnishing a dependable reference for clinical applications and future research endeavors. This aims to contribute significantly to the enhancement of cardiovascular health and overall well-being among elderly individuals.
Secondary gas in debris discs released following the decay of long-lived radioactive nuclides, catastrophic, or resurfacing collisions
Authors: Bonsor Amy , Wyatt Mark C , Marino Sebastian , Davidsson Björn J R , Kral Quentin , Thebault Philippe
Published: September 2023

Kuiper-like belts of planetesimals orbiting stars other than the Sun are most commonly detected from the thermal emission of small dust produced in collisions. Emission from gas, most notably CO, highlights the cometary nature of these planetesimals. Here, we present models for the release of gas from comet-like bodies in these belts, both due to their thermophysical evolution, most notably the decay of long-lived radioactive nuclides, and collisional evolution, including catastrophic and gentler resurfacing collisions. We show that the rate of gas release is not proportional to the rate of dust release, if non-catastrophic collisions or thermal evolution dominate the release of CO gas. In this case, care must be taken when inferring the composition of comets. Non-catastrophic collisions dominate the gas production at earlier times than catastrophic collisions, depending on the properties of the planetesimal belt. We highlight the importance of the thermal evolution of comets, including crucially the decay of long-lived radioactive nuclides, as a source of CO gas around young (<50 Myr) planetary systems, if large (10–100 km) planetesimals are present.
Compact and quiescent circumgalactic medium and Ly α haloes around extremely red quasars
Authors: Gillette Jarred , Lau Marie Wingyee , Hamann Fred , Perrotta Serena , Rupke David S N , Wylezalek Dominika , Zakamska Nadia L , Vayner Andrey
Published: September 2023

Red quasars may represent a young stage of galaxy evolution that provide important feedback to their host galaxies. We are studying a population of extremely red quasars (ERQs) with exceptionally fast and powerful outflows, at median redshift z = 2.6. We present Keck/Keck Cosmic Web Imager integral field spectra of 11 ERQs, which have median colour i–W3 = 5.9 mag, median 〈 Lbol 〉 ≈ 5 × 1047 erg s−1, Ly α halo luminosity 〈 Lhalo 〉 = 5 × 1043 erg s−1, and maximum linear size >128 kpc. The ERQ haloes are generally similar to blue quasar haloes, following known trends with Lbol in halo properties. ERQs have halo symmetries similar to Type-I blue quasars, suggesting Type-I spatial orientations. ERQ 〈 Lhalo 〉 is ∼2-dex below blue quasars, which is marginal due to scatter, but consistent with obscuration lowering photon escape fractions. ERQ haloes tend to have more compact and circularly symmetric inner regions than blue quasars, with median exponential scale lengths ∼9 kpc, compared with ∼16 kpc for blue quasars. When we include the central regions not available in blue quasar studies (due to point spread function problems), the true median ERQ halo scale length is just ∼6 kpc. ERQ haloes are kinematically quiet, with median velocity dispersion 293 km s−1, consistent with expected virial speeds. Overall, we find no evidence for feedback on circumgalactic scales, and the current episode of quasar activity (perhaps due to long outflow travel times) has not been around long enough to affect the circumgalactic medium. We confirm the narrow Ly α-emission spikes found in ERQ aperture spectra are halo features, and are useful for systemic redshifts and measuring outflow speeds in other features.
Bridging the gap in the mass–size relation of compact galaxies with MaNGA
Authors: Grèbol-Tomàs P , Ferré-Mateu A , Domínguez-Sánchez H
Published: September 2023

We present the analysis of the full Mapping Nearby Galaxies at APO (MaNGA) DR17 sample to characterize its population of compact galaxies. We focus on galaxies that fill the stellar mass (M⋆) gap between compact elliptical galaxies (cEs; 8 ≲ log (M⋆/M⊙) ≲ 10) and compact massive galaxies (CMGs; 10 ≲ log (M⋆/M⊙)). We study their stellar populations and kinematics to reveal how their properties depend on stellar mass. We select compact galaxies in the MaNGA DR17 sample according to their effective radius (Re) and stellar mass. 37 galaxies fulfill our selection criteria in the bridging region between cEs and CMGs. We derive their kinematics and stellar population parameters from the stacked spectra at 1 Re using a full spectral fitting routine. We then classify the selected compact galaxies in three main groups based on their stellar population properties. One of the groups shows characteristics compatible with relic galaxies, i.e. galaxies that have remained mostly unchanged since their early formation epoch (z ∼ 2). Another group shows more extended and continuous star formation histories (SFHs). The third group shows a low star-forming rate at initial times, which increases at around ∼4 Gyr. We compare the derived properties of the selected galaxies with those of previously studied compact galaxies at different mass ranges. The selected galaxies successfully fill the mass gap between cEs and CMGs. Their properties are compatible with the assumption that the scaling relations of compact galaxies at different mass ranges are related, although galaxies in the first group are clear outliers in the fundamental plane, suggesting different formation mechanisms for this relic population.
Watching ion-driven kinetics of ribozyme folding and misfolding caused by energetic and topological frustration one molecule at a time
Authors: Hori Naoto , Thirumalai D
Published: September 2023

Folding of ribozymes into well-defined tertiary structures usually requires divalent cations. How Mg2+ ions direct the folding kinetics has been a long-standing unsolved problem because experiments cannot detect the positions and dynamics of ions. To address this problem, we used molecular simulations to dissect the folding kinetics of the Azoarcus ribozyme by monitoring the path each molecule takes to reach the folded state. We quantitatively establish that Mg2+ binding to specific sites, coupled with counter-ion release of monovalent cations, stimulate the formation of secondary and tertiary structures, leading to diverse pathways that include direct rapid folding and trapping in misfolded structures. In some molecules, key tertiary structural elements form when Mg2+ ions bind to specific RNA sites at the earliest stages of the folding, leading to specific collapse and rapid folding. In others, the formation of non-native base pairs, whose rearrangement is needed to reach the folded state, is the rate-limiting step. Escape from energetic traps, driven by thermal fluctuations, occurs readily. In contrast, the transition to the native state from long-lived topologically trapped native-like metastable states is extremely slow. Specific collapse and formation of energetically or topologically frustrated states occur early in the assembly process.
cfOmics: a cell-free multi-Omics database for diseases
Authors: Li Mingyang , Zhou Tianxiu , Han Mingfei , Wang Hongke , Bao Pengfei , Tao Yuhuan , Chen Xiaoqing , Wu Guansheng , Liu Tianyou , Wang Xiaojuan , Lu Qian , Zhu Yunping , Lu Zhi John
Published: September 2023

Liquid biopsy has emerged as a promising non-invasive approach for detecting, monitoring diseases, and predicting their recurrence. However, the effective utilization of liquid biopsy data to identify reliable biomarkers for various cancers and other diseases requires further exploration. Here, we present cfOmics, a web-accessible database (https://cfomics.ncRNAlab.org/) that integrates comprehensive multi-omics liquid biopsy data, including cfDNA, cfRNA based on next-generation sequencing, and proteome, metabolome based on mass-spectrometry data. As the first multi-omics database in the field, cfOmics encompasses a total of 17 distinct data types and 13 specimen variations across 69 disease conditions, with a collection of 11345 samples. Moreover, cfOmics includes reported potential biomarkers for reference. To facilitate effective analysis and visualization of multi-omics data, cfOmics offers powerful functionalities to its users. These functionalities include browsing, profile visualization, the Integrative Genomic Viewer, and correlation analysis, all centered around genes, microbes, or end-motifs. The primary objective of cfOmics is to assist researchers in the field of liquid biopsy by providing comprehensive multi-omics data. This enables them to explore cell-free data and extract profound insights that can significantly impact disease diagnosis, treatment monitoring, and management.
Childhood, adolescent, and adult primary brain and central nervous system tumor statistics for practicing healthcare providers in neuro-oncology, CBTRUS 2015–2019
Authors: Price Mackenzie , Ryan Katherine , Shoaf Madison L , Neff Corey , Iorgulescu J Bryan , Landi Daniel B , Cioffi Gino , Waite Kristin A , Kruchko Carol , Barnholtz-Sloan Jill S , Ostrom Quinn T
Published: September 2023

Background

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI), is the largest aggregation of histopathology-specific population-based data for primary brain and other central nervous system (CNS) in the US. CBTRUS publishes an annual statistical report which provides critical reference data for the broad neuro-oncology community. Here, we summarize the key findings from the 2022 CBTRUS annual statistical report for healthcare providers.

Methods

Incidence data were obtained from the CDC’s National Program of Cancer Registries (NPCR) and NCI’s Surveillance, Epidemiology, and End Results Program for 52 central cancer registries (CCRs). Survival data were obtained from 42 NPCR CCRs. All rates are per 100 000 and age-adjusted using the 2000 US standard population. Overall median survival was estimated using Kaplan–Meier models. Survival data for selected molecularly defined histopathologies are from the National Cancer Database. Mortality data are from the National Vital Statistics System.

Results

The average annual age-adjusted incidence rate of all primary brain and other CNS tumors was 24.25/100 000. Incidence was higher in females and non-Hispanics. The most commonly occurring malignant and predominately non-malignant tumors was glioblastoma (14% of all primary brain tumors) and meningioma (39% of all primary brain tumors), respectively. Mortality rates and overall median survival varied by age, sex, and histopathology.

Conclusions

This summary describes the most up-to-date population-based incidence, mortality, and survival, of primary brain and other CNS tumors in the US and aims to serve as a concise resource for neuro-oncology providers.
Torsade de pointes during an oral surgery caused by a combination of herbal medicine-induced pseudoaldosteronism and trigeminocardiac reflex
Authors: Kawatani Yohei , Hoshi Kentaro , Yamada Hitoshi , Hori Takaki
Published: September 2023

Licorice can cause pseudoaldosteronism and QT prolongation as its side effect. Trigeminal nerve stimulation, including surgical intervention involving the face, can cause transient bradycardia, known as the trigeminocardiac reflex. Although rare, a combination of these two etiologies can cause ventricular tachycardia. A 50-year-old female patient with a history of hypertension and intake of an herbal drug containing licorice underwent impacted wisdom tooth extraction under general anesthesia. Immediately after placing a month-long prop for visualization in the oral cavity, sinus bradycardia occurred, followed by ventricular tachycardia and torsade de pointes. Mouth prop was removed and cardiopulmonary resuscitation was initiated, and the arrhythmia was resolved. Hypokalemia, metabolic alkalosis and normal aldosterone levels were observed. An inverted T wave and a prominent U-wave were observed on the electrocardiogram. Potassium excretion in urine was normal, although hypokalemia was present. The patient was treated with potassium correction.
Anti-neutrophil cytoplasmic antibody associated vasculitis of the brain and oral cavity: a case report
Authors: Bontempo D , Frydrych A M , Kujan O , Gebauer D , Fallon M , Panegyres P K
Published: September 2023

We report a patient with a novel presentation of anti-neutrophil cytoplasmic antibody positive (ANCA+) vasculitis of the brain and oral mucosa. ANCA+ vasculitis of the brain is usually associated with pachymeningitis and hypophysitis, and there are no cases reported with simultaneous brain and oral mucosal involvement. A 35-year-old African Zambian man presented with headache and bleeding swollen gingiva. He was myeloperoxidase (MPO) antibody positive with cytoplasmic staining. His MRI showed stable small callosal, periventricular and subcortical white matter non-enhancing lesions, without change over 15 months—compatible with vasculitis. His gingival biopsy was consistent with vasculitis. His headache and oral lesions responded to oral corticosteroids and intravenous immunoglobulin which have induced clinical remission. Our patient expands the clinical syndrome of ANCA+ MPO+ C-type vasculitis of the central nervous system with headaches complicating cerebral vasculitis and oral mucosal involvement.
Genome-wide association studies identify loci controlling specialized seed metabolites in Arabidopsis
Authors: Naake Thomas , Zhu Feng , Alseekh Saleh , Scossa Federico , Perez de Souza Leonardo , Borghi Monica , Brotman Yariv , Mori Tetsuya , Nakabayashi Ryo , Tohge Takayuki , Fernie Alisdair R
Published: September 2023

Plants synthesize specialized metabolites to facilitate environmental and ecological interactions. During evolution, plants diversified in their potential to synthesize these metabolites. Quantitative differences in metabolite levels of natural Arabidopsis (Arabidopsis thaliana) accessions can be employed to unravel the genetic basis for metabolic traits using genome-wide association studies (GWAS). Here, we performed metabolic GWAS on seeds of a panel of 315 A. thaliana natural accessions, including the reference genotypes C24 and Col-0, for polar and semi-polar seed metabolites using untargeted ultra-performance liquid chromatography-mass spectrometry. As a complementary approach, we performed quantitative trait locus (QTL) mapping of near-isogenic introgression lines between C24 and Col-0 for specific seed specialized metabolites. Besides common QTL between seeds and leaves, GWAS revealed seed-specific QTL for specialized metabolites, indicating differences in the genetic architecture of seeds and leaves. In seeds, aliphatic methylsulfinylalkyl and methylthioalkyl glucosinolates associated with the ALKENYL HYDROXYALKYL PRODUCING loci (GS-ALK and GS-OHP) on chromosome 4 containing alkenyl hydroxyalkyl producing 2 (AOP2) and 3 (AOP3) or with the GS-ELONG locus on chromosome 5 containing methylthioalkyl malate synthase (MAM1) and MAM3. We detected two unknown sulfur-containing compounds that were also mapped to these loci. In GWAS, some of the annotated flavonoids (kaempferol 3-O-rhamnoside-7-O-rhamnoside, quercetin 3-O-rhamnoside-7-O-rhamnoside) were mapped to transparent testa 7 (AT5G07990), encoding a cytochrome P450 75B1 monooxygenase. Three additional mass signals corresponding to quercetin-containing flavonols were mapped to UGT78D2 (AT5G17050). The association of the loci and associating metabolic features were functionally verified in knockdown mutant lines. By performing GWAS and QTL mapping, we were able to leverage variation of natural populations and parental lines to study seed specialized metabolism. The GWAS data set generated here is a high-quality resource that can be investigated in further studies.
Cell cycle status of male and female gametes during Arabidopsis reproduction
Authors: Voichek Yoav , Hurieva Bohdana , Michaud Caroline , Schmücker Anna , Vergara Zaida , Desvoyes Bénédicte , Gutierrez Crisanto , Nizhynska Viktoria , Jaegle Benjamin , Borg Michael , Berger Frédéric , Nordborg Magnus , Ingouff Mathieu
Published: September 2023

Fertilization in Arabidopsis (Arabidopsis thaliana) is a highly coordinated process that begins with a pollen tube delivering the 2 sperm cells into the embryo sac. Each sperm cell can then fertilize either the egg or the central cell to initiate embryo or endosperm development, respectively. The success of this double fertilization process requires a tight cell cycle synchrony between the male and female gametes to allow karyogamy (nuclei fusion). However, the cell cycle status of the male and female gametes during fertilization remains elusive as DNA quantification and DNA replication assays have given conflicting results. Here, to reconcile these results, we quantified the DNA replication state by DNA sequencing and performed microscopic analyses of fluorescent markers covering all phases of the cell cycle. We show that male and female Arabidopsis gametes are both arrested prior to DNA replication at maturity and initiate their DNA replication only during fertilization.
When tainted money should fund public goods: fundraising professional and public moral preferences
Authors: Rahwan Zoe , Leuker Christina
Published: September 2023

Philanthropy is essential to public goods such as education and research, arts and culture, and the provision of services to those in need. Providers of public goods commonly struggle with the dilemma of whether to accept donations from morally tainted donors. Ethicists also disagree on how to manage tainted donations. Forgoing such donations reduces opportunities for societal well-being and advancement; however, accepting them can damage institutional and individual reputations. Half of professional fundraisers have faced tainted donors, but only around a third of their institutions had relevant policies (n = 52). Here, we draw on two large samples of US laypeople (ns = 2,019; 2,566) and a unique sample of experts (professional fundraisers, n = 694) to provide empirical insights into various aspects of tainted donations that affect moral acceptability: the nature of the moral taint (criminal or morally ambiguous behavior), donation size, anonymity, and institution type. We find interesting patterns of convergence (rejecting criminal donations), divergence (professionals’ aversion to large tainted donations), and indifference (marginal role of anonymity) across the samples. Laypeople also applied slightly higher standards to universities and museums than to charities. Our results provide evidence of how complex moral trade-offs are resolved differentially, and can thus motivate and inform policy development for institutions dealing with controversial donors.
Evaluation of serious infections, including Mycobacterium tuberculosis, during treatment with biologic disease-modifying anti-rheumatic drugs: does line of therapy matter?
Authors: Lauper Kim , Kearsley-Fleet Lianne , Galloway James B , Watson Kath D ,   BSRBR-RA Contributors Group, Hyrich Kimme L , Lunt Mark
Published: September 2023

Objectives

This study aimed to evaluate if and how the incidence of serious infection (SI) and active tuberculosis (TB) differ among seven biologic DMARDs (bDMARDs) in patients with RA considering the line of therapy.

Methods

Patients with RA from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) cohort who initiated etanercept, certolizumab, infliximab, adalimumab, abatacept, rituximab or tocilizumab from the first to fifth line of therapy were included. Follow-up extended up to 3 years. The primary outcome was SI and the secondary outcome was TB. Event rates were calculated and compared using Cox proportional hazards models, controlling for confounding with inverse probability of treatment weights. Comparisons were made overall and stratified by line of therapy. Sensitivity analysis was restricted to all treatment courses from 2009 (tocilizumab availability) until the end of the study (2018).

Results

Among 33 897 treatment courses (62 513 patient-years) the incidence of SI was 4.4/100 patient-years (95% CI 4.2, 4.5). After adjustment, hazards ratios (HRs) of SI were slightly higher with adalimumab and infliximab compared with etanercept. However, no clear pattern was observed when stratifying by line of therapy in terms of incidence rate or HR. Sensitivity analyses showed similar HRs among these treatments. Regarding TB, all 49 cases occurred during the first three lines of treatment and rarely since 2009.

Conclusion

The risk of serious infections does not appear to be influenced by the line of therapy in patients with RA. However, the risk of TB seems to be more frequent during the initial lines of treatment or prior to 2009.
Persisting mortality gap in systemic lupus erythematosus; a population-based study on juvenile- and adult-onset SLE in Norway 1999–2022
Authors: Moe Sigrid Reppe , Haukeland Hilde , Brunborg Cathrine , Botea Antonela , Damjanic Nenad , Wivestad Gro Årthun , Øvreås Heidi , Bøe Thea , Orre Anniken , Garen Torhild , Lilleby Vibke , Provan Sella A , Molberg Øyvind , Lerang Karoline
Published: September 2023

Objective

To estimate mortality and survival rates of SLE in a contemporary, population-based setting and assess potential influences by time, sex, ethnicity, classification criteria and age at diagnosis.

Methods

We assessed mortality and survival in the Nor-SLE cohort, which includes all chart review–confirmed SLE cases resident in Southeast Norway (population 2.9 million) 1999–2017. Study end was at death, emigration or 1 October 2022. We defined juvenile SLE by age <16 years at diagnosis. For standardized mortality rate (SMR) estimates, we applied 15 population controls per case, all matched for age, sex, residency and ethnicity. We analysed survival by Kaplan–Meier and risk factors by Cox regression.

Results

The Nor-SLE cohort included 1558 SLE cases, of whom 749 were incident and met the 2019 EULAR and ACR (2019-EA) classification criteria. SMR was increased to 1.8 (95% CI 1.6–2.2) in incident adult-onset SLE but did not differ between females and males. Survival rates at 5, 10, 15 and 20 years were lower in incident adult-onset SLE than in matched controls. In multivariable analysis, LN associated with decreased survival, while sex did not. Separate, long-term mortality analyses in the total Nor-SLE cohort showed that SMR peaked at 7.2 (95% CI 3.3–14) in juvenile-onset SLE (n = 93) and fell gradually by increasing age at SLE diagnosis.

Conclusion

This study shows persistence of a mortality gap between adult-onset SLE and controls at population level and provides indications of worryingly high mortality in juvenile-onset SLE.