bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Histo-endoscopic Remission but not Endoscopic Healing Alone in Ulcerative Colitis is Associated with a Mucosal Transcriptional Profile Resembling Healthy Mucosa
Authors: Hernández-Rocha Cristian , Nayeri Shadi , Turpin Williams , Steel Mike , Borowski Krzysztof , Stempak Joanne M , Conner James , Silverberg Mark S 
Published: January 2022

Abstract

Background and Aims
A composite endpoint of histological and endoscopic remission is proposed to be the most complete measure of mucosal healing in ulcerative colitis [UC]. We aim to establish the prognosis, and transcriptional and microbial features of histo-endoscopic remission and activity.

Methods
A cross-sectional endoscopic rectosigmoid colon sample collection from UC patients and healthy controls [HC] was performed for histopathology and host genome-wide RNA-sequencing. Histo-endoscopic remission and histo-endoscopic activity were defined as Mayo endoscopic subscore [MES] 0–1 with and without histological activity, respectively. UC relapse, defined as symptomatic and endoscopic worsening, was retrospectively recorded for survival analysis. Unsupervised and differential gene expression analyses were performed, and the interaction between transcriptomics and mucosal gut microbiota was analysed based on the 16S rRNA gene sequencing profile.

Results
UC patients with histo-endoscopic remission showed a significantly lower risk of relapse compared to histo-endoscopic activity. Unsupervised analysis of the transcriptomic profile showed that histo-endoscopic remission and histo-endoscopic activity samples clustered with HC and MES 2–3 samples, respectively. A total of 452 host genes enriched for humoral immune response, antimicrobial defence, chemokine and TH17 signalling pathway were upregulated in histo-endoscopic activity compared to histo-endoscopic remission. A set of host genes with antimicrobial properties showed significant associations with mucosal microbiota.

Conclusions
The rectosigmoid mucosa transcriptional profile of UC patients in histo-endoscopic remission resembles that of HC mucosa and confers a lower risk of relapse. These data support that the combination of histo-endoscopic remission could be the most appropriate definition of mucosal healing in UC.
Acute lower respiratory infections: real-world evidence of antibiotic prescription pattern and costs from a large administrative Italian database
Authors: Calabria Silvia , Dondi Letizia , Ronconi Giulia , Piccinni Carlo , Pedrini Antonella , Esposito Immacolata , Addesi Alice , Maggioni Aldo Pietro , Martini Nello 
Published: January 2022

Abstract

Objective
This observational retrospective analysis aimed to describe antibiotic prescription pattern in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and community-acquired pneumonia (CAP) and their costs, from the Italian National Health Service perspective.

Methods
From the ReS database, a cross-linkage of Italian healthcare administrative databases through a unique anonymous code allowed to select subjects aged ≥12 years, supplied with at least an antibacterial for systemic use (ATC code: J01) from 01/01/2017 to 12/31/2017 and evaluable until the end of 2018. Prescriptions of different antibiotics on the same date were excluded. The prescription pattern was assessed for patients with an AECOPD (aged ≥50) or a CAP event (aged ≥12) in 2017. A 30-day cost analysis after the antibacterial supply and according to absence/presence (15 days before/after the supply) of AECOPD/CAP hospitalization was performed.

Results
In 2017, among patients aged ≥12 (~5 million), 1,845,268 were supplied with ≥1 antibacterial (37.2%). Antibacterial prescriptions potentially related to AECOPD were 39,940 and 4,059 to CAP: quinolones were the most prescribed (37.2% and 39.0%, respectively), followed by third-generation cephalosporins (25.5%; 27.5%), penicillins (15.4%; 14.9%), and macrolides (14.4%; 11.3%); the 30-day mean cost was €709 and €2,889. An association AECOPD/CAP-antibacterial supply costed more when the hospitalization occurred 15 days after the antibiotic supply (€5,006 and €4,966, respectively).

Conclusions
Findings confirmed the very high use of antimicrobials in Italy and highlighted the urgent need of improving current prescribing practices and developing new molecules, to stop the incessant spread of antimicrobial resistance and related socioeconomic impacts.
Automatic measurement and quality control of S3KS-SKKS differential traveltimes and the influence of mantle heterogeneity
Authors: Ji Qing , Zhao Li 
Published: January 2022

SUMMARY
The velocity structure of the uppermost part of the outer core can be investigated seismologically based on the differential traveltimes between the SKKS and S3KS waves (S3KS-SKKS). We develop a procedure for the automatic measurement and quality assessment of the S3KS-SKKS differential traveltime measurements. Four criteria with empirically determined thresholds are used to quantify the quality of the measurements in our automatic algorithm, which greatly simplifies the data quality control. Measurements obtained in the epicentral distance range of 120–140° display positive residuals relative to PREM with no obvious spatial dependency. Waveform simulations in both PREM and S40RTS models show that neither finite-frequency effects nor large-scale mantle heterogeneities can fully explain the magnitude of the observed residuals. Mantle heterogeneities have a significant contribution to the data uncertainty, but do not have sufficient effect on the mean finite-frequency correction. We thus conclude that the observed residuals in the S3KS-SKKS differential traveltimes after finite-frequency correction are mainly caused by the velocity structure in the uppermost outer core.
2-D joint inversion of semi-airborne CSEM and LOTEM data in eastern Thuringia, Germany
Authors: Cai Ji , Yogeshwar Pritam , Mörbe Wiebke , Smirnova Maria , Haroon Amir , Becken Michael , Tezkan Bülent 
Published: January 2022

SUMMARY
Various electromagnetic (EM) techniques have been developed for exploring natural resources. The novel frequency-domain semi-airborne controlled source electromagnetic (semi-AEM) method takes advantages of both ground and airborne techniques. It combines ground-based high-power electrical dipole sources with large-scale and spatially densely covered magnetic fields measured via airborne receivers. The method can survey the subsurface down to approximately 1000 m and is particularly sensitive towards conductive bodies (e.g. mineralized bodies) in a more resistive host environment. However, the signal-to-noise ratio of semi-AEM is lower than that of ground-based methods such as long-offset transient electromagnetics (LOTEM), mainly due to the limited stacking time and motion-induced noise. As a result, the semi-AEM often has reduced depth of investigation in comparison to LOTEM. One solution to overcome these flaws is to analyse and interpret semi-AEM data together with information from other EM methods using a joint inversion. Since our study shows that LOTEM and semi-AEM data have complementary subsurface resolution capabilities, we present a 2-D joint inversion algorithm to simultaneously interpret frequency-domain semi-AEM data and transient electric fields using extended dipole sources. The algorithm has been applied to the field data acquired in a former mining area in eastern Thuringia, Germany. The 2-D joint inversion combines the complementary information and provides a meaningful 2-D resistivity model. Nevertheless, obvious discrepancies appear between the individual and joint inversion results. Consequent synthetic modelling studies illustrate that the discrepancies occur because of (i) differences in lateral and depth resolution between the semi-AEM and LOTEM data caused by different measuring configurations, (ii) different measured EM components and (iii) differences in the error weighting of the individual data sets. Additionally, our synthetic study suggests that more flexible land-based configurations with sparse receiver locations are possible in combination with semi-AEM without a significant loss of target resolution, which is promising for accelerating data acquisition and for survey planning and logistics, particularly when measuring in inaccessible areas.
Secular variation signals in magnetic field gradient tensor elements derived from satellite-based geomagnetic virtual observatories
Authors: Hammer Magnus D , Finlay Christopher C , Olsen Nils 
Published: January 2022

SUMMARYWe present local time-series of the magnetic field gradient tensor elements at satellite altitude derived using a Geomagnetic Virtual Observatory (GVO) approach. Gradient element time-series are computed in 4-monthly bins on an approximately equal-area distributed worldwide network. This enables global investigations of spatio-temporal variations in the gradient tensor elements. Series are derived from data collected by the Swarm and CHAMP satellite missions, using vector field measurements and their along-track and east–west differences, when available. We find evidence for a regional secular variation impulse (jerk) event in 2017 in the first time derivative of the gradient tensor elements. This event is located at low latitudes in the Pacific region. It has a similar profile and amplitude regardless of the adopted data selection criteria and is well fit by an internal potential field. Spherical harmonic models of the internal magnetic field built from the GVO gradient series show lower scatter in near-zonal harmonics compared with models built using standard GVO vector field series. The GVO gradient element series are an effective means of compressing the spatio-temporal information gathered by low-Earth orbit satellites on geomagnetic field variations, which may prove useful for core flow inversions and in geodynamo data assimilation studies.
The impact of vent geometry on the growth of lava domes
Authors: Mériaux Catherine A , May Dave A , Jaupart Claude 
Published: January 2022

SUMMARY
Thick lava flows that are a feature of many volcanic fields on the Earth and Venus vary from sheet-like to nearly perfect axisymmetric domes. Here, we investigate how these geometrical characteristics depend on the shape of the feeder vent. We study the gravitational spreading of viscous lava erupting from elliptical vents onto a flat surface using 3-D numerical models. The aspect ratio of the vent, defined to be the major to minor axes ratio, varies between 1 and 25. In the limit of an aspect ratio of one, the vent is circular and spreading is axisymmetric. In the limit where the ratio is large, the vent behaves as a fissure. The numerical models rely on an isoviscous lava rheology and a constant volumetric eruption rate. In all cases, the initial phase of the dome’s evolution is in a lava-discharge dominated regime such that spreading is insignificant and the height of the dome increases at a constant rate over the vent area. For vent aspect ratios greater than five, three successive regimes of spreading are identified: 2-D spreading in the direction perpendicular to the major axis of the vent, a transient phase such that the dome shape evolves towards that of a circular dome and a late axisymmetric spreading phase that does not depend on the vent shape. These regimes are delimited by the times required for the flow thickness above the vent to reach a given height and for the flow to spread axisymmetrically up to a length equal to the semi-major axis of the vent. Numerical results for the flow height and runout length tend towards the similarity solutions in the 2-D and axisymmetric regimes. Two main implications for highly viscous (rhyolitic) fissure eruptions can be drawn. First, the fissure length determines the flow regimes. The longer the vent fissure length, the longer the early lava discharge regime and 2-D spreading perpendicular to the length of the fissure. Second, the aspect ratio of fissure-fed lava flows can be used as an indicator of the fissure length and the duration of lava discharge. The ellipticity of some terrestrial fissure-fed flows provides evidence for viscous gravity-driven spreading terminated before the onset of the axisymmetric regime. On the other hand, the circular domes on Venus appear to be the result of fissure-fed eruptions sustained enough for the spreading to reach the axisymmetric regime. We propose relationships providing estimates of the fissure length and the duration of lava discharge based on fossil dome dimensions.
Pathogenic SLC25A26 variants impair SAH transport activity causing mitochondrial disease
Authors: Rosenberger Florian A , Tang Jia Xin , Sergeant Kate , Moedas Marco F , Zierz Charlotte M , Moore David , Smith Conrad , Lewis David , Guha Nishan , Hopton Sila , Falkous Gavin , Lam Amanda , Pyle Angela , Poulton Joanna , Gorman Gráinne S , Taylor Robert W , Freyer Christoph , Wredenberg Anna 
Published: January 2022

Abstract
The SLC25A26 gene encodes a mitochondrial inner membrane carrier that transports S-adenosylmethionine (SAM) into the mitochondrial matrix in exchange for S-adenosylhomocysteine (SAH). SAM is the predominant methyl-group donor for most cellular methylation processes, of which SAH is produced as a by-product. Pathogenic, biallelic SLC25A26 variants are a recognized cause of mitochondrial disease in children, with a severe neonatal onset caused by decreased SAM transport activity. Here, we describe two, unrelated adult cases, one of whom presented with recurrent episodes of severe abdominal pain and metabolic decompensation with lactic acidosis. Both patients had exercise intolerance and mitochondrial myopathy associated with biallelic variants in SLC25A26, which led to marked respiratory chain deficiencies and mitochondrial histopathological abnormalities in skeletal muscle that are comparable to those previously described in early-onset cases. We demonstrate using both mouse and fruit fly models that impairment of SAH, rather than SAM, transport across the mitochondrial membrane is likely the cause of this milder, late-onset phenotype. Our findings associate a novel pathomechanism with a known disease-causing protein and highlight the quests of precision medicine in optimizing diagnosis, therapeutic intervention and prognosis.
Ancestry- and sex-specific effects underlying inguinal hernia susceptibility identified in a multiethnic genome-wide association study meta-analysis
Authors: Choquet Hélène , Li Weiyu , Yin Jie , Bradley Rachael , Hoffmann Thomas J , Nandakumar Priyanka ,   23 and Me Research Team, Mostaedi Rouzbeh , Tian Chao , Ahituv Nadav , Jorgenson Eric 
Published: January 2022

Abstract
Inguinal hernias are some of the most frequently diagnosed conditions in clinical practice and inguinal hernia repair is the most common procedure performed by general surgeons. Studies of inguinal hernias in non-European populations are lacking, though it is expected that such studies could identify novel loci. Further, the cumulative lifetime incidence of inguinal hernia is nine times greater in men than women, however, it is not clear why this difference exists. We conducted a genome-wide association meta-analysis of inguinal hernia risk across 513 120 individuals (35 774 cases and 477 346 controls) of Hispanic/Latino, African, Asian and European descent, with replication in 728 418 participants (33 491 cases and 694 927 controls) from the 23andMe, Inc dataset. We identified 63 genome-wide significant loci (P &lt; 5 × 10−8), including 41 novel. Ancestry-specific analyses identified two loci (LYPLAL1-AS1/SLC30A10 and STXBP6-NOVA1) in African ancestry individuals. Sex-stratified analyses identified two loci (MYO1D and ZBTB7C) that are specific to women, and four (EBF2, EMX2/RAB11FIP2, VCL and FAM9A/FAM9B) that are specific to men. Functional experiments demonstrated that several of the associated regions (EFEMP1 and LYPLAL1-SLC30A10) function as enhancers and show differential activity between risk and reference alleles. Our study highlights the importance of large-scale genomic studies in ancestrally diverse populations for identifying ancestry-specific inguinal hernia susceptibility loci and provides novel biological insights into inguinal hernia etiology.
Hsa-miR223-3p circulating level is upregulated in Friedreich’s ataxia and inversely associated with HCLS1 associated protein X-1, HAX-1
Authors: Quatrana Andrea , Morini Elena , Tiano Francesca , Vancheri Chiara , Panarello Luca , Romano Silvia , Marcotulli Christian , Casali Carlo , Mariotti Caterina , Mongelli Alessia , Fichera Mario , Rufini Alessandra , Condò Ivano , Novelli Giuseppe , Testi Roberto , Amati Francesca , Malisan Florence 
Published: January 2022

Abstract
Frataxin (FXN) deficiency is responsible for Friedreich’s ataxia (FRDA) in which, besides the characteristic features of spinocerebellar ataxia, two thirds of patients develop hypertrophic cardiomyopathy that often progresses to heart failure and premature death. Different mechanisms might underlie FRDA pathogenesis. Among them, the role of miRNAs deserves investigations. We carried out an miRNA PCR-array analysis of plasma samples of early-, intermediate- and late-onset FRDA groups, defining a set of 30 differentially expressed miRNAs. Hsa-miR223-3p is the only miRNA shared between the three patient groups and appears upregulated in all of them. The up-regulation of hsa-miR223-3p was further validated in all enrolled patients (n = 37, Fc = +2.3; P &lt; 0.0001). Using a receiver operating characteristic curve analysis, we quantified the predictive value of circulating hsa-miR223-3p for FRDA, obtaining an area under the ROC curve value of 0.835 (P &lt; 0.0001) for all patients. Interestingly, we found a significant positive correlation between hsa-miR223-3p expression and cardiac parameters in typical FRDA patients (onset &lt; 25 years). Moreover, a significant negative correlation between hsa-miR223-3p expression and HAX-1 (HCLS1-associated protein X-1) at mRNA and protein level was observed in all FRDA patients. In silico analyses suggested HAX-1 as a target gene of hsa-miR223-3p. Accordingly, we report that HAX-1 is negatively regulated by hsa-miR223-3p in cardiomyocytes (AC16) and neurons (SH-SY5Y), which are critically affected cell types in FRDA. This study describes for the first time the association between hsa-miR223-3p and HAX-1 expression in FRDA, thus supporting a potential role of this microRNA as non-invasive epigenetic biomarker for FRDA.
Relationship Between Dissociation and Antidepressant Effects of Esketamine Nasal Spray in Patients With Treatment-Resistant Depression
Authors: Chen Guang , Chen Li , Zhang Yun , Li Xiang , Lane Rosanne , Lim Pilar , Daly Ella J , Furey Maura L , Fedgchin Maggie , Popova Vanina , Singh Jaskaran B , Drevets Wayne C 
Published: January 2022

Abstract

Background
In this post-hoc analysis, data from 2 positive, pivotal, phase 3 trials of esketamine nasal spray (ESK) in treatment-resistant depression (TRD)—short-term study (TRANSFORM-2) and maintenance study (SUSTAIN-1)—were analyzed to evaluate the relationship between dissociation and antidepressant effects of ESK.

Methods
Analysis by responder status, correlation analysis, and mediation analysis were performed to assess the relationships between peak Clinician Administered Dissociative States Scale (CADSS) scores after first (day 1) and last (day 25) ESK dose and change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores at the first (day 2) and last assessments (day 28) in TRANSFORM-2 and peak CADSS after first maintenance ESK dose and time to relapse in SUSTAIN-1 (only for mediation analysis).

Results
In TRANSFORM-2, the percentage of responders (&gt;50% reduction in MADRS) at day 2 and day 28 did not significantly differ between patients who did vs did not manifest significant dissociation (peak CADSS scores &gt;4 or ≤4, respectively) following the first ESK dose. Spearman correlation coefficients between dissociation and depression improvement were nonsignificant and close to zero. CADSS scores did not significantly mediate the reduction in MADRS at day 2 or 28 in TRANSFORM-2 or the time to depression relapse in SUSTAIN-1. The mean difference in MADRS between ESK and active-control arms persisted beyond day 2 without significant change across time, although the mean peak CADSS scores significantly decreased across consecutive doses and fewer patients experienced significant dissociation after the last ESK dose compared with the first.

Conclusion
Within the dose range tested, the dissociative and antidepressant effects of ESK were not significantly correlated.

Trial registration
NCT02417064 (TRANSFORM-1); NCT02418585(TRANSFORM-2); NCT02493868 (SUSTAIN-1)
Serotonin 1A Receptor Binding of [11C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response
Authors: Lan Martin J , Zanderigo Francesca , Pantazatos Spiro P , Sublette M Elizabeth , Miller Jeffrey , Ogden R Todd , Mann J John 
Published: January 2022

Abstract

Background
The pathophysiology of bipolar disorder (BD) remains largely unknown despite it causing significant disability and suicide risk. Serotonin signaling may play a role in the pathophysiology, but direct evidence for this is lacking. Treatment of the depressed phase of the disorder is limited. Previous studies have indicated that positron emission tomography (PET) imaging of the serotonin 1A receptor (5HT1AR) may predict antidepressant response.

Methods
A total of 20 participants with BD in a current major depressive episode and 16 healthy volunteers had PET imaging with [11C]CUMI-101, employing a metabolite-corrected input function for quantification of binding potential to the 5HT1AR. Bipolar participants then received an open-labeled, 6-week clinical trial with a selective serotonin reuptake inhibitor (SSRI) in addition to their mood stabilizer. Clinical ratings were obtained at baseline and during SSRI treatment.

Results
Pretreatment binding potential (BPF) of [11C]CUMI-101 was associated with a number of pretreatment clinical variables within BD participants. Within the raphe nucleus, it was inversely associated with the baseline Montgomery Åsberg Rating Scale (P = .026), the Beck Depression Inventory score (P = .0023), and the Buss Durkee Hostility Index (P = .0058), a measure of lifetime aggression. A secondary analysis found [11C]CUMI-101 BPF was higher in bipolar participants compared with healthy volunteers (P = .00275). [11C]CUMI-101 BPF did not differ between SSRI responders and non-responders (P = .907) to treatment and did not predict antidepressant response (P = .580). Voxel-wise analyses confirmed the results obtained in regions of interest analyses.

Conclusions
A disturbance of serotonin system function is associated with both the diagnosis of BD and its severity of depression. Pretreatment 5HT1AR binding did not predict SSRI antidepressant outcome.
The study was listed on clinicaltrials.gov with identifier NCT02473250.
Cohomological Blowups of Graded Artinian Gorenstein Algebras along Surjective Maps
Authors: Iarrobino Anthony , Macias Marques Pedro , McDaniel Chris , Seceleanu Alexandra , Watanabe Junzo 
Published: January 2022

Abstract
We introduce the cohomological blowup of a graded Artinian Gorenstein algebra along a surjective map, which we term BUG (blowup Gorenstein) for short. This is intended to translate to an algebraic context the cohomology ring of a blowup of a projective manifold along a projective submanifold. We show, among other things, that a BUG is a connected sum, that it is the general fiber in a flat family of algebras, and that it preserves the strong Lefschetz property. We also show that standard graded compressed algebras are rarely BUGs, and we classify those BUGs that are complete intersections. We have included many examples throughout this manuscript.