bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute pancreatitis coincided with multiple arteriolar aneurysms in a patient with polyarteritis nodosa
Authors: Takamatsu Ko , Kusanagi Yasuyoshi , Horikoshi Hideyuki , Nakanishi Takashi , Wada Akinori , Koumoto Shunsuke , Katsurada Yuka , Tsuda Hitoshi , Hokari Ryota , Kimura Fumihiko , Itoh Kenji 
Published: December 2021

ABSTRACT
A 78-year-old man presented to our hospital with a history of 10 kg weight loss within 6 months previously and general fatigue and fever for 2 and 1 months, respectively. On hospitalisation, the patient was diagnosed with polyarteritis nodosa after multiple microaneurysms were observed in the liver, kidney, pancreas, and mesenteries. He achieved remission with the administration of 1000 mg methylprednisolone for 3 days, followed by prednisolone (55 mg/day). Steroids were successfully tapered with no re-elevation in inflammation. Two months after the administration of steroids, the patient complained of acute abdominal pain and developed severe acute pancreatitis. During treatment for pancreatitis, the patient died due to septic shock and disseminated intravascular coagulation. An autopsy revealed necrotising vasculitis in the intrapancreatic arteries and ischaemia of the downstream arterioles resulting in acute pancreatitis.
TIN2 is an architectural protein that facilitates TRF2-mediated trans- and cis-interactions on telomeric DNA
Authors: Kaur Parminder , Barnes Ryan , Pan Hai , Detwiler Ariana C , Liu Ming , Mahn Chelsea , Hall Jonathan , Messenger Zach , You Changjiang , Piehler Jacob , Smart Robert C , Riehn Robert , Opresko Patricia L , Wang Hong 
Published: December 2021

Abstract
The telomere specific shelterin complex, which includes TRF1, TRF2, RAP1, TIN2, TPP1 and POT1, prevents spurious recognition of telomeres as double-strand DNA breaks and regulates telomerase and DNA repair activities at telomeres. TIN2 is a key component of the shelterin complex that directly interacts with TRF1, TRF2 and TPP1. In vivo, the large majority of TRF1 and TRF2 are in complex with TIN2 but without TPP1 and POT1. Since knockdown of TIN2 also removes TRF1 and TRF2 from telomeres, previous cell-based assays only provide information on downstream effects after the loss of TRF1/TRF2 and TIN2. Here, we investigated DNA structures promoted by TRF2–TIN2 using single-molecule imaging platforms, including tracking of compaction of long mouse telomeric DNA using fluorescence imaging, atomic force microscopy (AFM) imaging of protein–DNA structures, and monitoring of DNA–DNA and DNA–RNA bridging using the DNA tightrope assay. These techniques enabled us to uncover previously unknown unique activities of TIN2. TIN2S and TIN2L isoforms facilitate TRF2-mediated telomeric DNA compaction (cis-interactions), dsDNA–dsDNA, dsDNA–ssDNA and dsDNA–ssRNA bridging (trans-interactions). Furthermore, TIN2 facilitates TRF2-mediated T-loop formation. We propose a molecular model in which TIN2 functions as an architectural protein to promote TRF2-mediated trans and cis higher-order nucleic acid structures at telomeres.
Kinetic explanations for the sequence biases observed in the nonenzymatic copying of RNA templates
Authors: Ding Dian , Zhou Lijun , Giurgiu Constantin , Szostak Jack W 
Published: December 2021

Abstract
The identification of nonenzymatic pathways for nucleic acid replication is a key challenge in understanding the origin of life. We have previously shown that nonenzymatic RNA primer extension using 2-aminoimidazole (2AI) activated nucleotides occurs primarily through an imidazolium-bridged dinucleotide intermediate. The reactive nature and preorganized structure of the intermediate increase the efficiency of primer extension but remain insufficient to drive extensive copying of RNA templates containing all four canonical nucleotides. To understand the factors that limit RNA copying, we synthesized all ten 2AI-bridged dinucleotide intermediates and measured the kinetics of primer extension in a model system. The affinities of the ten dinucleotides for the primer/template/helper complexes vary by over 7,000-fold, consistent with nearest neighbor energetic predictions. Surprisingly, the reaction rates at saturating intermediate concentrations still vary by over 15-fold, with the most weakly binding dinucleotides exhibiting a lower maximal reaction rate. Certain noncanonical nucleotides can decrease sequence dependent differences in affinity and primer extension rate, while monomers bridged to short oligonucleotides exhibit enhanced binding and reaction rates. We suggest that more uniform binding and reactivity of imidazolium-bridged intermediates may lead to the ability to copy arbitrary template sequences under prebiotically plausible conditions.
Probing the mechanisms of two exonuclease domain mutators of DNA polymerase ϵ
Authors: Dahl Joseph M , Thomas Natalie , Tracy Maxwell A , Hearn Brady L , Perera Lalith , Kennedy Scott R , Herr Alan J , Kunkel Thomas A 
Published: December 2021

Abstract
We report the properties of two mutations in the exonuclease domain of the Saccharomyces cerevisiae DNA polymerase ϵ. One, pol2-Y473F, increases the mutation rate by about 20-fold, similar to the catalytically dead pol2-D290A/E290A mutant. The other, pol2-N378K, is a stronger mutator. Both retain the ability to excise a nucleotide from double-stranded DNA, but with impaired activity. pol2-Y473F degrades DNA poorly, while pol2-N378K degrades single-stranded DNA at an elevated rate relative to double-stranded DNA. These data suggest that pol2-Y473F reduces the capacity of the enzyme to perform catalysis in the exonuclease active site, while pol2-N378K impairs partitioning to the exonuclease active site. Relative to wild-type Pol ϵ, both variants decrease the dNTP concentration required to elicit a switch between proofreading and polymerization by more than an order of magnitude. While neither mutation appears to alter the sequence specificity of polymerization, the N378K mutation stimulates polymerase activity, increasing the probability of incorporation and extension of a mismatch. Considered together, these data indicate that impairing the primer strand transfer pathway required for proofreading increases the probability of common mutations by Pol ϵ, elucidating the association of homologous mutations in human DNA polymerase ϵ with cancer.
Are sex differences in the outcome of peritoneal dialysis explained by nurse assistance? A cohort study with data from the Registre de Dialyse Péritonéale de Langue Française
Authors: Danneville Isabelle , Beaumier Mathilde , Chatelet Valérie , Boyer Annabel , Lanot Antoine , Bechade Clémence , Lobbedez Thierry 
Published: December 2021

ABSTRACT

Background
We aimed to evaluate sex differences in peritoneal dialysis (PD) outcomes and to explore direct and indirect effects of nurse-assisted PD on outcomes.

Methods
This was a retrospective study using data from the Registre de Dialyse Péritonéale de Langue Française of incident PD patients between 2005 and 2016. Cox proportional hazards modelling was used to analyse transfer to haemodialysis (HD), death, PD failure, peritonitis and renal transplantation. Mediation analyses with a counterfactual approach were carried out to evaluate natural direct and indirect effects of sex on transfer to HD and peritonitis, with nurse-assisted PD as a mediator a priori.

Results
Of the 14 659 patients included, there were 5970 females (41%) and 8689 males (59%). Women were more frequently treated by nurse-assisted PD than men [2926/5970 (49.1%) versus 3357/8689 (38.7%)]. In the multivariable analysis, women had a lower risk of transfer to HD [cause-specific hazard ratio {cs-HR} 0.82 {95% confidence interval (CI) 0.77–0.88}], death [cs-HR 0.90 (95% CI 0.85–0.95)], peritonitis [cs-HR 0.82 (95% CI 0.78–0.87)], PD failure [cs-HR 0.86 (95% CI 0.83–0.90)] and a lower chance of undergoing transplant [cs-HR 0.83 (95% CI 0.77–0.90)] than men. There was a direct effect of sex on the risk of transfer to HD [cs-HR 0.82 (95% CI 0.82–0.83)], with an indirect effect of nurse-assisted PD [cs-HR 0.97 (95% CI 0.96–0.99)]. Nurse-assisted PD had no indirect effect on the risk of peritonitis.

Conclusions
Our results suggest that compared with men, women have a lower risk of both transfer to HD and peritonitis. Mediation analysis showed that nurse assistance was a potential mediator in the causal pathway between sex and transfer to HD.
Associations Between Noticing Nicotine Vaping Product Health Warning Labels, Harm Perceptions, and Use Among Adult Vapers, Current and Former Smokers. Findings From the 2018 ITC Four Country Smoking and Vaping Survey
Authors: Taylor Eve , Aleyan Sarah , East Katherine , Michael Cummings K , Thrasher James F , Fong Geoffrey T , Quah Anne C K , Li Grace , Borland Ron , Hammond David , Hitchman Sara C 
Published: December 2021

Abstract

Background
The number of countries mandating a nicotine addiction warning label (“warnings”) on nicotine vaping products (NVPs) has been increasing. This study examined associations between noticing NVP warnings, perceptions of NVPs, and intentions to use NVPs.

Aim and Methods
Cross-sectional analysis of 12 619 adult NVP users, cigarette smokers, concurrent users of both cigarettes and NVPs, and quitters who participated in the 2018 International Tobacco Control (ITC) Project Four Country Smoking and Vaping Survey (England, Australia, Canada, USA). Logistic regression analyses examined associations between noticing warnings in the past 30 days and perceptions of nicotine harm, NVP harm relative to cigarettes, and NVP addictiveness relative to cigarettes. Associations were also explored between noticing warnings and intentions to use NVPs.

Results
Noticing warnings was higher among NVP users (18.8%) than nonusers (2.1%). Noticing warnings was associated with perceiving nicotine to pose little or no harm to health among NVP users, but there was no association among nonusers. There was little evidence of an association between noticing warnings and perceptions of NVP harms relative to smoking among NVP users and non-users. Noticing warnings was associated with perceiving NVPs as less addictive than cigarettes among nonusers but not NVP users. Among exclusive smokers, noticing warnings was associated with intending to start using NVPs. Among NVP users, there was little evidence of an association between noticing warnings and intentions to continue using/stopping NVPs.

Conclusions
Noticing NVP warnings was not associated with increased NVP and nicotine harm perceptions or decreased intentions to use NVPs among adult smokers and vapers.

Implications
Our findings suggest that noticing NVP warnings may not influence NVP risk perceptions or deter NVP use among adult smokers and vapers. Future research should investigate the impact of warnings on youth and adults who have never smoked or vaped.
Lipid Changes After Switch From TDF to TAF in the OPERA Cohort: LDL Cholesterol and Triglycerides
Authors: Mallon Patrick W G , Brunet Laurence , Fusco Jennifer S , Prajapati Girish , Beyer Andrew , Fusco Gregory P , Wohlfeiler Michael B 
Published: December 2021

Abstract

Background
Increases in lipids have been observed in people with HIV (PWH) switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We assessed changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) following a switch from TDF to TAF.

Methods
Adults with ≥1 lipid measure before and after switch from TDF to TAF were identified in the OPERA cohort. Multivariable linear regression using generalized estimating equations was used to estimate predicted changes in lipids over time on TAF, modeled flexibly with linear splines.

Results
A total of 6451 PWH switched from TDF to TAF, of whom 4328 maintained all other agents. LDL-C increased significantly by 1.40 mg/dL/mo over the first 3 months on TAF, by 0.33 mg/dL/mo between 3 and 9 months and then plateauing beyond 9 months. TG increased significantly by 3.52 mg/dL/mo over the first 3 months of TAF, by 0.91 mg/mL/mo between 3 and 9 months and by 0.72 mg/mL/mo between 9 and 16 months, but decreased thereafter. Similar patterns were observed in analyses restricted to PWH who switched from TDF to TAF but maintained all other agents.

Conclusions
TDF-to-TAF switch was associated with LDL-C and TG increases over the first 9 to 16 months on TAF. The dynamic patterns observed cannot be attributed to changes in other agents.
Tele-monitoring flares using a smartphone app in patients with gout or suspected gout: a feasibility study
Authors: Pouls Bart P H , Bekker Charlotte L , Gaffo Angelo L , van den Bemt Bart J F , Flendrie Marcel 
Published: December 2021

AbstractObjectivesGout flares are painful and disabling. We developed a smartphone application (app) for patients to tele-monitor gout flares surveyed by clinicians. The aim of this study was to assess patient acceptability and technical and clinical feasibility.MethodsAdult patients with either established gout or high suspicion thereof were recruited if they possessed a smartphone and reported a recent arthritis attack. A smartphone application was used to identify gout flares by asking during 90 consecutive days: (1) what is your pain score (0–10); (2) are your joints warm; (3) are your joints swollen; and (4) are you currently experiencing a gout flare? The clinician was alerted via email if a flare occurred. Patient acceptability was assessed using the technology acceptance model. Technical feasibility consisted of reported technical issues and clinical feasibility of actions taken by the clinician regarding gout flare alerts.ResultsTwenty-nine included patients completed the study. The mean age of participants was 57 years, and all but one were male. The adherence rate was 96% (110 of 2910 queries were missed). Patients had a positive attitude toward app use, found the app very easy to use (mean usability score 81 out of 100) and were neutral to positive on its usefulness. There were four minor technical issues. A total of 100 gout flare alerts were generated that led to 18 proactive contacts with patients.ConclusionA smartphone app to monitor gout flares was developed and tested, showing high adherence, good acceptability and clinical feasibility for established gout patients.Trial registrationNetherlands Trial Register, https://www.trialregister.nl, NL6435.
SARS-CoV-2 vaccine in patients with systemic sclerosis: impact of disease subtype and therapy
Authors: Sampaio-Barros Percival Degrava , Medeiros-Ribeiro Ana Cristina , Luppino-Assad Ana Paula , Miossi Renata , da Silva Henrique Carriço , Yuki Emily F V N , Pasoto Sandra G , Saad Carla G S , Silva Clóvis A , Kupa Léonard V K , Deveza Giordano B H , Pedrosa Tatiana N , Aikawa Nádia E , Bonfá Eloisa 
Published: December 2021

Abstract

Objective
To analyse the safety, immunogenicity and factors affecting antibody response to Severe Acute Respiratory Syndrome–Coronavirus–2 (SARS-CoV-2) vaccination in patients with SSc.

Methods
This is a phase 4 prospective study within a larger trial of two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in 51 SSc patients compared with 153 controls. Anti-SARS-CoV-2-IgG and neutralizing antibodies (NAb) were assessed at each vaccine shot (D0/D28) and 6 weeks after the second dose(D69), only in individuals with negative baseline IgG/NAb and those who did not have coronavirus-19(COVID19) during follow-up. Vaccine safety was also assessed in all participants.

Results
Patients and controls had comparable median ages [48(38.5–57) vs 48(38–57) years, P =0.945]. Patients had mostly diffuse SSc (68.6%) and the majority (74.5%) had interstitial lung disease. Most patients were under immunosuppressive therapy (72.5%), mainly MMF (52.9%). After full vaccination (D69), anti-SARS-CoV-2-IgG frequency (64.1% vs 94.2%, P &lt; 0.001) and NAb positivity (53.8% vs 76.9%; P =0.006) were moderate, although lower than controls. The first dose response (D28) was low and comparable for both seroconvertion rates (SC) (P =0.958) and NAb positivity (P =0.537). SSc patients under MMF monotherapy vs other (no therapy/other DMARDs) had lower immunogenicity (SC: 31.3% vs 90%, P &lt; 0.001) and NAb(18.8% vs 85%, P &lt; 0.001). Multiple regression analysis confirmed that MMF use, but not disease subtype, is associated with insufficient seroconversion [odds ratio (OR)=0.056(95% CI: 0.009, 0.034), P =0.002] and NAb positivity [OR = 0.047(95% CI: 0.007, 0.036), P =0.002]. No moderate/severe side-effects were observed.

Conclusion
CoronaVac has an excellent safety profile and moderate response to anti-SARS-CoV-2 vaccine in SSc. Vaccine antibody response is not influenced by disease subtype and is greatly affected by MMF, reinforcing the need for additional strategies to up-modulate vaccine response in this subgroup of patients.

Trial registration
ClinicalTrials.gov, https://clinicaltrials.gov, NCT04754698
Elevated Th17 cells are associated with cardiovascular complications in ankylosing spondylitis
Authors: Ding Tingting , Li Baochen , Su Rui , Su Ronghui , Wang Yanyan , Gao Chong , Li Xiaofeng , Wang Caihong 
Published: December 2021

Abstract

Objective
Patients with ankylosing spondylitis (AS) carry an increased burden of cardiovascular diseases (CVD), but features denoting the development of CVD in AS are unclear. This study aimed to evaluate the percentage and absolute number of lymphocytes and CD4+T cells in AS patients complicated with CVD (AS-CVD) and determine whether circulating T helper 17 (Th17) cells are associated with the development of CVD in AS.

Method
A total of 117 AS patients (46 had CVD and 71 had no CVD) were enrolled in this retrospective study. The percentage and absolute number of lymphocytes and CD4+T cells were determined by flow cytometry. Associations between CVD and clinical markers were analysed using logistic regression.

Results
The ratio of Th17/Treg cells (0.30 vs 0.19, P = 0.014) and the absolute number of Th17 cells (7.27 cells/μL vs 4.34 cells/μL, P &lt; 0.001) was significantly elevated in AS-CVD group compared with AS-no-CVD group. Multivariate logistic regression revealed that elevated Th17 cells (OR = 1.20, P = 0.016) were associated with CVD complications in AS. Receiver operating characteristic (ROC) curves showed a contribution of Th17 cell for distinguishing AS patients with CVD, with the areas under the ROC curve (AUCs) of 0.729 (95% CI: 0.632, 0.825, P &lt; 0.001).

Conclusion
Our findings provide evidence for the association between Th17 cells and increased cardiovascular risk in AS. Th17 cells may contribute to accelerated atherogenesis and increased cardiovascular burden in AS and be valuable for early assessment and management of AS-CVD.
Attainment of low disease activity and remission targets reduces the risk of severe flare and new damage in childhood lupus
Authors: Smith Eve M D , Tharmaratnam Kukatharmini , Al-Abadi Eslam , Armon Kate , Bailey Kathryn , Brennan Mary , Ciurtin Coziana , Gardner-Medwin Janet , Haslam Kirsty E , Hawley Daniel , Leahy Alice , Leone Valentina , Malik Gulshan , McLaren Zoe , Pilkington Clarissa , Ramanan Athimalaipet V , Rangaraj Satyapal , Ratcliffe Annie , Riley Philip , Sen Ethan , Sridhar Arani , Wilkinson Nick , Hedrich Christian M , Jorgensen Andrea , Beresford Michael W 
Published: December 2021

Abstract

Objectives
To assess the achievability and effect of attaining low disease activity (LDA) or remission in childhood-onset SLE (cSLE).

Methods
Attainment of three adult-SLE derived definitions of LDA (LLDAS, LA, Toronto-LDA), and four definitions of remission (clinical-SLEDAI-defined remission on/off treatment, pBILAG-defined remission on/off treatment) was assessed in UK JSLE Cohort Study patients longitudinally. Prentice–Williams–Petersen gap recurrent event models assessed the impact of LDA/remission attainment on severe flare/new damage.

Results
LLDAS, LA and Toronto-LDA targets were reached in 67%, 73% and 32% of patients, after a median of 18, 15 or 17 months, respectively. Cumulatively, LLDAS, LA and Toronto-LDA was attained for a median of 23%, 31% and 19% of total follow-up-time, respectively. Remission on-treatment was more common (61% cSLEDAI-defined, 42% pBILAG-defined) than remission off-treatment (31% cSLEDAI-defined, 21% pBILAG-defined). Attainment of all target states, and disease duration (&gt;1 year), significantly reduced the hazard of severe flare (P &lt; 0.001). As cumulative time in each target increased, hazard of severe flare progressively reduced. LLDAS attainment reduced the hazard of severe flare more than LA or Toronto-LDA (P &lt; 0.001). Attainment of LLDAS and all remission definitions led to a statistically comparable reduction in the hazards of severe flare (P &gt; 0.05). Attainment of all targets reduced the hazards of new damage (P &lt; 0.05).

Conclusions
This is the first study demonstrating that adult-SLE-derived definitions of LDA/remission are achievable in cSLE, significantly reducing risk of severe flare/new damage. Of the LDA definitions, LLDAS performed best, leading to a statistically comparable reduction in the hazards of severe flare to attainment of clinical remission.
Shell features and anatomy of the springsnail genus Radomaniola (Caenogastropoda: Hydrobiidae) show a different pace and mode of evolution over five million years
Authors: Delicado Diana , Hauffe Torsten 
Published: December 2021

Abstract
Shell features are key factors for systematics and evolutionary biology studies of freshwater gastropods. Based mostly on shell morphology, 19 species of the springsnail genus Radomaniola (family Hydrobiidae) have been described. Although the scarce differentiation of various shell dimensions suggests morphological stasis, the evolutionary dynamics of shell and other anatomical structures have not yet been explored fully. By inferring a phylogeny and a time-calibrated species tree from mitochondrial (COI and 16S) and nuclear (28S) sequences of 15 recognized species, we initially examine the species diversity of the Radomaniola dataset and then, through phylogenetic comparative methods, assess the evolutionary correlation, pace and mode of 40 continuous shell and anatomical characters. By synthesizing the results of four species delimitation methods and through morphological examinations, we recognize 21 groups, for which taxonomy is discussed here. Seven new species are described. We reveal a high degree of correlated evolution between characters of the shell, which are constrained by a single morphological optimum, consistent with the morphological stasis model. Anatomical traits diverged rapidly in an unconstrained manner or toward multiple optima. These findings indicate that in order to understand the morphological evolution of springsnails, it is essential to examine different organs in detail.