bluuebunny/crossref_metadata_2025 huggingface dataset:
812 Prognostic impact of the COAPT inclusion and exclusion criteria in real-world patients with secondary mitral regurgitation undergoing MitraClip implantation
Authors: Serratore Serena , Polimeni Alberto , Mongiardo Annalisa , Spaccarotella Carmen , Sorrentino Sabato , Panuccio Giuseppe , Cacia Michele , Lucchino Alessandro , Scebba Jacopo , Durante Pierfrancesco , Trapuzzano Albino , Ciliberto Federica , De Rosa Salvatore , Indolfi Ciro
Published: December 2021

Aims

The COAPT randomized trial has shown a huge benefit in the survival of patients with s heart failure and functional mitral regurgitation treated with MitraClip. However, patients in COAPT were highly selected and the clinical course in real-world patients with and without fulfilment of the trial inclusion criteria is unclear.

Methods

The present study examined the clinical outcome in consecutive patients with symptomatic moderate-to-severe or severe MR of dominant functional aetiology undergoing MitraClip therapy by the presence of the inclusion criteria of the COAPT trial (left ventricular ejection fraction >20%, left ventricular end-systolic dimension <70 mm, non-commissural primary jet, estimated pulmonary artery systolic pressure <70 mmHg, mitral valve orifice area >4 cm2, no prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve or any prior transcatheter mitral valve procedure).

Results

The composite endpoint of all-cause mortality or heart failure hospitalization and the endpoint of heart failure hospitalization were analysed. Among 118 patients who underwent MitraClip implantation 61% fulfilled the inclusion criteria of COAPT. The composite endpoint was significantly less frequent (P = 0.05) in patients fulfilling the COAPT selection criteria than in those not fulfilling the criteria, with an estimated 1-year event rate of 25% vs. 49%. Heart failure hospitalization was significantly less frequent (P = 0.04) in patients fulfilling COAPT selection criteria than in those who did not, with an estimated 1-year event rate of 19% vs. 36.8%.

Conclusions

In this single centre study the outcome of patients with functional mitral regurgitation undergoing MitraClip therapy was significantly worse in patients not fulfilling COAPT inclusion criteria, indicating that these criteria might help identify futility.
The genome sequence of the avian vampire fly (Philornis downsi), an invasive nest parasite of Darwin’s finches in Galápagos
Authors: Romine Melia G , Knutie Sarah A , Crow Carly M , Vaziri Grace J , Chaves Jaime A , Koop Jennifer A H , Lamichhaney Sangeet
Published: December 2021

The invasive avian vampire fly (Philornis downsi, Diptera: Muscidae) is considered one of the greatest threats to the endemic avifauna of the Galápagos Islands. The fly larvae parasitize nearly every passerine species, including Darwin’s finches. Most P. downsi research to date has focused on the effects of the fly on avian host fitness and mitigation methods. A lag in research related to the genetics of this invasion demonstrates, in part, the need to develop full-scale genomic resources with which to address further questions within this system. In this study, an adult female P. downsi was sequenced to generate a high-quality genome assembly. We examined various features of the genome (e.g., coding regions and noncoding transposable elements) and carried out comparative genomics analysis against other dipteran genomes. We identified lists of gene families that are significantly expanding or contracting in P. downsi that are related to insecticide resistance, detoxification, and counter defense against host immune responses. The P. downsi genome assembly provides an important resource for studying the molecular basis of successful invasion in the Galápagos and the dynamics of its population across multiple islands. The findings of significantly changing gene families associated with insecticide resistance and immune responses highlight the need for further investigations into the role of different gene families in aiding the fly’s successful invasion. Furthermore, this genomic resource provides a necessary tool to better inform future research studies and mitigation strategies aimed at minimizing the fly’s impact on Galápagos birds.
Comparative Immunogenicity and Effectiveness of mRNA-1273, BNT162b2, and Ad26.COV2.S COVID-19 Vaccines
Authors: Naranbhai Vivek , Garcia-Beltran Wilfredo F , Chang Christina C , Berrios Mairena Cristhian , Thierauf Julia C , Kirkpatrick Grace , Onozato Maristela L , Cheng Ju , St Denis Kerri J , Lam Evan C , Kaseke Clarety , Tano-Menka Rhoda , Yang Diane , Pavlovic Maia , Yang Wendy , Kui Alexander , Miller Tyler E , Astudillo Michael G , Cahill Jennifer E , Dighe Anand S , Gregory David J , Poznansky Mark C , Gaiha Gaurav D , Balazs Alejandro B , Iafrate A John
Published: December 2021

Background

Understanding immunogenicity and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is critical to guide rational use.

Methods

We compared the immunogenicity of mRNA-1273, BNT-162b2, and Ad26.COV2.S in healthy ambulatory adults. We performed an inverse-variance meta-analysis of population-level effectiveness from public health reports in > 40 million individuals.

Results

A single dose of either mRNA vaccine yielded comparable antibody and neutralization titers to convalescent individuals. Ad26.COV2.S yielded lower antibody concentrations and frequently undetectable neutralization titers. Bulk and cytotoxic T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients. Regardless of vaccine, <50% of vaccinees demonstrated CD8+ T-cell responses. Antibody concentrations and neutralization titers increased comparably after the first dose of either vaccine, and further in recipients of a second dose. Prior infection was associated with high antibody concentrations and neutralization even after a single dose and regardless of vaccine. Neutralization of Beta, Gamma, and Delta strains were poorer regardless of vaccine. In meta-analysis, relative to mRNA1273 the effectiveness of BNT162b2 was lower against infection and hospitalization, and Ad26COV2.S was lower against infection, hospitalization, and death.

Conclusions

Variation in the immunogenicity correlates with variable effectiveness of the 3 vaccines deployed in the United States.
More Challenging Diets Sustain Feeding Performance: Applications Toward the Captive Rearing of Wildlife
Authors: Mitchell D Rex , Wroe Stephen , Ravosa Matthew J , Menegaz Rachel A
Published: December 2021

Synopsis

The rescue and rehabilitation of young fauna is of substantial importance to conservation. However, it has been suggested that incongruous diets offered in captive environments may alter craniofacial morphology and hinder the success of reintroduced animals. Despite these claims, to what extent dietary variation throughout ontogeny impacts intrapopulation cranial biomechanics has not yet been tested. Here, finite element models were generated from the adult crania of 40 rats (n = 10 per group) that were reared on 4 different diet regimes and stress magnitudes compared during incisor bite simulations. The diets consisted of (1) exclusively hard pellets from weaning, (2) exclusively soft ground pellet meal from weaning, (3) a juvenile switch from pellets to meal, and (4) a juvenile switch from meal to pellets. We hypothesized that a diet of exclusively soft meal would result in the weakest adult skulls, represented by significantly greater stress magnitudes at the muzzle, palate, and zygomatic arch. Our hypothesis was supported at the muzzle and palate, indicating that a diet limited to soft food inhibits bone deposition throughout ontogeny. This finding presents a strong case for a more variable and challenging diet during development. However, rather than the “soft” diet group resulting in the weakest zygomatic arch as predicted, this region instead showed the highest stress among rats that switched as juveniles from hard pellets to soft meal. We attribute this to a potential reduction in number and activity of osteoblasts, as demonstrated in studies of sudden and prolonged disuse of bone. A shift to softer foods in captivity, during rehabilitation after injury in the wild for example, can therefore be detrimental to healthy development of the skull in some growing animals, potentially increasing the risk of injury and impacting the ability to access full ranges of wild foods upon release. We suggest captive diet plans consider not just nutritional requirements but also food mechanical properties when rearing wildlife to adulthood for reintroduction.
The arbitrability of antitrust disputes: a Chinese perspective
Authors: Bu Qingxiu
Published: December 2021

The cornerstone of public policy debate opens the door for arbitral tribunals to deal with antitrust disputes. It has long been a controversial issue whether antitrust disputes related to commercial contracts could be arbitrable, given the lack of clarity under Chinese law. China’s Supreme People’s Court in Shell v Huili has seemingly provided important but paradoxical guidance on non-arbitrability. Arguably, the ruling may be incompatible with the doctrine of international comity in the current transnational dispute resolution mechanism. It is argued that the operation costs for all stakeholders would be considerably reduced if China could integrate into the established international track.
A Survey of YouTube Videos as a Source of Useful/Unuseful Information in the Field of the Prevention and Management of Burn Injuries: A Cross-sectional Analysis of the English Language Content
Authors: Gurbuz Kayhan , Demir Mete , Das Koray
Published: December 2021

The study was designed on whether YouTube videos are useful as an information resource in the field of burn injury prevention and management. Current literature on the educational content and quality of burn-related first-aid videos on YouTube was reported as inadequate and inaccurate. However, the quality of YouTube videos on various medical and clinical topics has been the subject of many previous studies, and there has been increasing evidence that the content ratio of usefulness was higher than that of nonuseful. While hours and even minutes in burn injuries are as precious as gold in terms of outcomes, it would be a significant loss not to use the most popular and easily accessible free social media platform of our time as a tool that can contribute to the prevention of burns and raise awareness. Analysis was conducted with the remaining 96 videos from 240 videos obtained from YouTube, according to possible search terms and exclusion of videos according to predetermined criteria. The Global Quality Score (GQS) and modified DISCERN (m.DISCERN) tools were used to assess the quality and reliability of the videos. Viewer engagement metrics and video properties were also investigated according to the usefulness criteria (eg, video length, duration on YouTube, topic contents, source uploads, reliability, and quality). Finally, it was revealed that nearly 80% of the YouTube videos contained information in the field of the prevention and management of burn injuries deemed useful in this study, comparable to the other medical disciplines’ reports in the literature.
Online or Offline: Does It Matter? A Review of Existing Interpretation Approaches and Their Effect on Screening Mammography Metrics, Patient Satisfaction, and Cost
Authors: Ram Shruthi , Campbell Tyler , Lourenco Ana P
Published: December 2021

The ideal practice routine for screening mammography would optimize performance metrics and minimize costs, while also maximizing patient satisfaction. The main approaches to screening mammography interpretation include batch offline, non-batch offline, interrupted online, and uninterrupted online reading, each of which has its own advantages and drawbacks. This article reviews the current literature on approaches to screening mammography interpretation, potential effects of newer technologies, and promising artificial intelligence resources that could improve workflow efficiency in the future.
Impact of grazing on germination trait selection in an alpine grassland on the Tibet Plateau
Authors: Liu Yang , Liu Kun , Zhang Zhilong , Zhang Shiting , Baskin Carol C , Baskin Jerry M , Liang Ting , Bu Haiyan , Li Shuxia , Zhang Tingting , Cui Xianliang , Xiao Sa
Published: December 2021

Previous studies indicated that grazing can cause significant changes in abiotic and biotic environment in grassland. However, how these changes impact germination trait selection in grassland has not been well studied. Thus, we aimed to explore whether grazing can significantly change germination trait diversity and composition of grasslands community. We measured the germination traits of species in the laboratory, and compared their performance in grazed and nongrazed grasslands. Then, we compared the community-weighted means of germination traits and functional diversity of grazed and nongrazed grasslands based on these germination traits to know whether grazed and nongrazed grasslands differed in their germination trait structures. At the species level, we found that the changes of abundance in grazed and nongrazed grasslands were not related to species’ germination traits. However, at the community level, compared with nongrazed grasslands, species in the grazed grasslands generally exhibited a higher seed germination percentage. Moreover, seed germination response in grazed grasslands was more positively related to alternating temperature than in nongrazed grasslands, and breadth of the germination temperature niche was narrower in grazed than in nongrazed grasslands. Compared with nongrazed grasslands, seed germination trait diversity was increased and germination trait evenness decreased in grazed grasslands. Grazing can change microhabitat conditions, thereby changing germination trait selection by environmental filtering, resulting in a significant difference in germinate trait composition at the community level.
Patterns of grassland community composition and structure along an elevational gradient on the Qinghai–Tibet Plateau
Authors: Wang Xin , Zhu Jiangling , Peng Shitao , Zheng Tianli , Qi Zhaoyu , Hu Jianbo , Ji Chengjun
Published: December 2021

Grasslands in the Qinghai–Tibet Plateau play an important role in preserving ecological security and high biodiversity in this region. However, the distribution of the composition and structure of plant community and the mechanism by which it maintains itself in this region are still poorly understood. Here, we designed 195 grassland plots in 39 grassland sites along an approximately 1700 m elevation gradient on the Northeastern Qinghai–Tibet Plateau. We found that the grassland community height decreased significantly with increasing elevation, whereas community coverage did not significantly change. With increasing elevation, plant species richness (α diversity) increased significantly, but the community variability (β diversity) decreased significantly. The constrained clustering analysis suggested that the α- and β-diversity in the grasslands transformed gradually with elevation, and that three discontinuous points (based on community structure) were observed at elevation of 3640, 4252 and 4333 m. Structural equation modeling (SEM) indicated that the increase in precipitation and the decrease in temperature significantly positively influenced α diversity, which was negatively correlated with β diversity. These results demonstrate a quantitative-to-qualitative change in the community composition and structure along this elevational gradient on the Qinghai–Tibet Plateau.
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

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

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

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

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

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

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

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

Objectives

Gout 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.

Methods

Adult 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.

Results

Twenty-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.

Conclusion

A smartphone app to monitor gout flares was developed and tested, showing high adherence, good acceptability and clinical feasibility for established gout patients.

Trial registration

Netherlands 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

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 < 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 < 0.001) and NAb(18.8% vs 85%, P < 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

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 < 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 < 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

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 (>1 year), significantly reduced the hazard of severe flare (P < 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 < 0.001). Attainment of LLDAS and all remission definitions led to a statistically comparable reduction in the hazards of severe flare (P > 0.05). Attainment of all targets reduced the hazards of new damage (P < 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

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.
Introducing Mass Communications Strategies to Medical Students: A Novel Short Session for Fourth-Year Students
Authors: Krohn Kristina M. , Crichlow Renee , McKinney Zeke J. , Tessier Katelyn M. , Scheurer Johannah M. , Olson Andrew P.J.
Published: December 2021

Problem

The World Health Organization calls on all with quality medical information to share it with the public and combat health misinformation; however, U.S. medical schools do not currently teach students effective communication with lay audiences about health. Most physicians have inadequate training in mass communication strategies.

Approach

In August 2018, a novel 90-minute class at the University of Minnesota Medical School introduced fourth-year medical students to basic skills for communicating with lay audiences through mass media. Instructors were physicians with experience interacting with the general public via radio, op-ed articles, social media, print media, television, and community and legislative advocacy. After a 20-minute lecture and sharing of instructors’ personal experiences, students completed two 30-minute small-group activities. They identified communications objectives and talking points for a health topic, drafting these as Tweets or an op-ed article outline, then presented talking points in a mock press conference with their peers, practicing skills just learned. Pre- and postsurveys documented students’ previous engagement and comfort with future engagement with mass media messaging.

Outcomes

Over 1 week, 142 students participated in 6 separate classes, and 127 completed both pre- and postsurveys. Before the course, only 6% (7/127) of students had comfortably engaged with social media and 14% (18/127) had engaged with traditional media in their professional roles. After the course, students self-reported an increase in their comfort, perceived ability, and likelihood of using specific communications skills to advocate for their patients (all P < .001).

Next Steps

The course will be expanded into a 5-session thread for third- and fourth-year medical students spread over 2 years. This thread will include meeting physicians who engage with lay audiences, identifying best practices for mass health communication, identifying bias and misinformation, “dos and don’ts” of social media, and communication skills for legislative advocacy.
Rising to the Challenge: Strategies to Support Latinas and Other Women of Color in Science and Medicine
Authors: Rodriguez Carolyn I. , Jagsi Reshma , Mangurian Christina
Published: December 2021

Although the number of Hispanic/Latina women earning medical degrees has increased in recent years, the article by Anaya and colleagues in this issue highlights their stark underrepresentation in the U.S. physician workforce. In this Invited Commentary, the authors provide context on proposed drivers of underrepresentation, including bias, discrimination, harassment, and other structural barriers, which are amplified for women with multiple minoritized identities. They summarize the 2020 National Academies of Sciences, Engineering, and Medicine recommendations for supporting women in science, technology, engineering, mathematics, and medicine (STEMM) fields, including committed leadership, dedicated financial and human resources, data-driven accountability, and use of an intersectional approach to address the challenges faced by individuals who encounter multiple forms of bias and discrimination. The authors also provide additional recommendations and highlight innovative new National Institutes of Health funding opportunities to promote diversity in the scientific workforce. They argue that more research is needed to identify and best implement institutional practices that increase representation and retention of Latina women and other women with minoritized identities in STEMM fields.
The Crest Injection Technique for Glabellar Line Correction and the Paracentral Artery
Authors: Tansatit Tanvaa , Uruwan Sukanya , Rungsawang Chalermquan
Published: December 2021

The glabella is a zone that carries a high risk of blindness after performing filler injections. The arteries beneath the glabellar lines were investigated by meticulous dissections in 30 geriatric embalmed cadavers with latex injections into the arterial system. The results showed that the supratrochlear artery, a direct branch of the ophthalmic artery, ascended from the muscular layer of the medial eyebrow along the medial canthal vertical line of the intercanthal vertical zone (53 in 60 hemifaces, or 88%). The dominant single paracentral artery from the radix artery was found within the radix vertical zone (eight out of 30 glabellae, or 27%). Among these, the dominant paracentral artery was near the midline in two cadavers and arose along the radix vertical line in six cadavers. The dominant paracentral artery may be the cause of ocular complications during injections of glabellar lines between the medial eyebrows, especially at the radix vertical lines. The supratrochlear artery might cause ocular complications when an injection is performed close to the medial eyebrows. Pinching to create a skin crest and evert glabellar line for a precise injection is recommended to temporarily occlude the paracentral artery.
Impact of Railway Critical Incidents on Train Drivers and Effectiveness of Critical Incident Management and Support Protocols
Authors: Bardon Cécile , Dargis Luc , Mishara Brian L.
Published: December 2021

Objective:

Train drivers are regularly involved in railway critical incidents (CI) and critical incident management and support protocols (CIMSPs) have been developed to support them. This study describes the impact of CIs and evaluates the effectiveness of CIMSPs.

Methods:

We interviewed 74 train drivers 1 week, 1, 3, and 6 months after a CI. We performed Linear growth model analyses to describe recovery paths and the effect of CIMSPs, considering the effect of CI complexity, proximity to victims, social support, self-assessment of health, use of resources, and attribution of responsibility.

Results:

CIs have a significant negative impact on train drivers. Recovery paths can be explained by the level of implementation of CIMSPs, and other contributing factors.

Conclusions:

CIMSPs are effective in reducing the negative impact of CIs and should be implemented rigorously by employers.
Inter-rater Reliability of the Classification of the J-Sign Is Inadequate Among Experts
Authors: Hiemstra Laurie A. , Sheehan Brendan , Sasyniuk Treny M. , Kerslake Sarah
Published: December 2021

Objective:

The purpose of this study was to determine the inter-rater and intra-rater reliability of the symmetry, classification, and underlying pathoanatomy associated with the J-sign in patients with recurrent lateral patellofemoral instability.

Study design:

Blinded, inter-rater reliability study.

Setting:

N/A.

Participants:

Thirty patellofemoral joint experts.

Interventions:

Thirty clinicians independently assessed 30 video recordings of patients with recurrent lateral patellofemoral instability performing the J-sign test.

Main outcome measures:

Raters documented J-sign symmetry and graded it according to the quadrant and Donell classifications. Raters indicated the most significant underlying pathoanatomy and presence of sagittal plane maltracking. Intra-rater reliability was assessed by 4 raters repeating the assessments. Mean pairwise simple and/or weighted Cohen's kappa were performed to measure inter-rater and intra-rater reliability, as well as calculation of percent agreement.

Results:

J-sign symmetry demonstrated fair inter-rater reliability (k = 0.26), whereas intra-rater reliability was moderate (k = 0.48). Inter-rater reliability for the quadrant and Donell classifications indicated moderate agreement, k = 0.51 and k = 0.49, respectively, whereas intra-rater reliability was k = 0.79 and k = 0.72, indicating substantial agreement. Inter-rater reliability of the foremost underlying pathoanatomy produced only slight agreement (k = 0.20); however, intra-rater reliability was substantial (k = 0.68). Sagittal plane maltracking demonstrated slight inter-rater agreement (k = 0.23) but substantial intra-rater agreement (k = 0.64).

Conclusions:

The symmetry, classification, and underlying pathoanatomy of the J-sign demonstrated fair to moderate inter-rater reliability and moderate to substantial intra-rater reliability among expert reviewers using video recordings of patients with recurrent lateral patellofemoral instability. These findings suggest individual raters have a consistent standard for assessing the J-sign, but that these standards are not reliable between assessors.

Level of evidence:

III.