bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal stromal cells in the regeneration of radiation-induced organ sequelae: will they make the difference?
Authors: Benderitter M , Herrera-Reyes E , Tamarat R
Published: May 2022

Mesenchymal stromal cells (MSCs) are a stem cell product with good safety that demonstrate significant clinical efficacy in the treatment of different pathologies, including radiation diseases (e.g. radiological burns, pelvic radiation disease). While the first results for some first human applications for the treatment of radiation disease suggest benefit, larger trials with clinically important endpoints are needed before definitive conclusions can be drawn. However, the supply and cost of MSCs remain the two main limitations for this innovative therapeutic product. Exosomes (EXOs), a stem cell product associated with MSC therapy, have shown promising efficacy and safety in humans. MSC-EXO therapeutics represent a promising next-generation approach for treating radiation diseases involving a primary (major) inflammatory component. Provided that conditions for MSC-EXO production and bio-banking are agreed in the near future, the transition to industrial production of MSC-EXOs will be possible, and this is required to initiate well-controlled clinical trials for approval by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA).
Enhanced voltage response in TiO2 nanoparticle-embedded piezoelectric nanogenerator
Authors: Bhatta Sheetal , Mitra Rahul , Ramadoss Ananthakumar , Manju Unnikrishnan
Published: May 2022

Poly (vinylidene fluoride) (PVDF) and its copolymers have piqued a substantial amount of research interest for its use in modern flexible electronics. The piezoelectric β-phase of the polymers can be augmented with the addition of suitable fillers that promote β-phase nucleation. In this work, we report an improved output voltage response of poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) with the incorporation of 10 wt.% Titanium (IV) oxide nanoparticles into the polymer matrix. The nano-filler was dispersed in the polymer matrix to form nanocomposite films via the solution casting technique. X-ray Diffraction and Scanning Electron Microscopy measurements were performed to verify the structure and morphology of the films. Fourier Transform Infrared Spectroscopy revealed enhancement in the β-phase nucleation from ∼15% to ∼36% with the addition of 10 wt.% titania nanoparticles. Thermogravimetric analysis and Differential Scanning Calorimetry results show improved thermal stability of the nanocomposite film, up to 345 °C, as compared to pristine PVDF-HFP. We also demonstrate a facile method for the fabrication of a piezoelectric nanogenerator with β-PVDF-HFP/TiO2 nanocomposite as an active layer. The outputs from the fabricated nanogenerator reached up to 8.89 V through human finger tapping motions, paving way for its potential use in the field of sensors, actuators, and self-sustaining flexible devices.
Experiments for students with built-in theory: ‘PUMA: Spannungslabor’ – an augmented reality app for studying electricity
Authors: Stolzenberger Christoph , Frank Florian , Trefzger Thomas
Published: May 2022

With the help of augmented reality apps objects and text can be added virtually to the physical world (e.g. physical experiments) in real time. The augmented reality (AR) app ‘PUMA: Spannungslabor’ enhances simple electric circuits experiments for students with virtual representations based on the electron gas analogy including visualisations of interior processes in various components such as lamps and resistors. This opens up new possibilities for connecting theory and experiment in secondary school physics teaching. While using the AR app students are enabled to acquire qualitative and semi-quantitative knowledge about the basic concepts of current, voltage, potential, and resistance as well as the laws of series and parallel circuits easier and more directly. This holistic approach of learning through experiments can facilitate a deeper and more interconnected understanding of the topics covered in physics lessons.
Accelerated Gaussian quantum state transfer between two remote mechanical resonators
Authors: Rezaei M , Javidan K , Abdi M
Published: May 2022

The main challenge in deterministic quantum state transfer (QST) between remote mechanical resonators is the local decoherence and the transmission losses in the communication channel. In the path of overcoming this limitation, here we employ a shortcut to adiabatic passage protocol to devise a fast and reliable evolution path between two remote mechanical modes in separate optomechanical systems (OMSs). A QST between the two nodes is conceived by engineering their coupling to an intermediate fiber optical channel. The coupling pulses are operated such that the dark eigenmode of the system is decoupled from the fiber modes and transitions to the bright modes are compensated for by counterdiabatic drives. We show that one obtains a QST with high fidelity for various Gaussian states. The efficiency is compared to that of adiabatic passage (AP) protocol in the presence of losses and noises. Our results show that while the AP protocol is very sensitive to the decoherence, the shortcut to adiabaticity provides a robust and fast QST even for small values of the coupling strength. The performance of both protocols are also investigated for the case of multimode fiber through numerical and an effective single-model model which is found by the elimination of off-resonant fiber modes. Our findings may pave the way for using OMSs in the realization of continuous-variable Gaussian QST.
Color-kinematics duality for Sudakov form factor in non-supersymmetric pure Yang–Mills theory
Authors: Li Zeyu , Yang Gang , Zhang Jinxuan
Published: May 2022

We study the duality between color and kinematics for the Sudakov form factors oftr(F2)in non-supersymmetric pure Yang-Mills theory. We construct the integrands that manifest the color-kinematics duality up to two loops. The resulting numerators are given in terms of Lorentz products of momenta and polarization vectors, which have the same powers of loop momenta as that from the Feynman rules. The integrands are checked byd-dimensional unitarity cuts and are valid in any dimension. We find that massless-bubble and tadpole topologies are needed at two loops to realize the color-kinematics duality. Interestingly, the two-loop solution contains a large number of free parameters suggesting the duality may hold at higher loop orders.
Percolation of hyperspheres in dimensions 3 to 5: from discrete to continuous
Authors: Brzeski Piotr , Kondrat Grzegorz
Published: May 2022

We study the onset of percolation of overlapping discrete hyperspheres on hypercubic lattices in dimension D = 3, 4, 5. Taking the continuum limit of the thresholds for discrete hyperspheres we obtain the values of percolation thresholds for continuous hyperspheres. In D = 3 we improved the value of the correlation length exponent: ν = 0.8762(7). In D = 4 and 5 we obtained the continuous percolation thresholds of hyperspheres with much better quality than previously known (the uncertainties reduced by the factor of 230 and 10 respectively). We discuss the hypothesis of constant exponent governing the rate of convergence of discrete models to the continuous one for hyperspheres.
Future population exposure to Australian heatwaves
Authors: Nishant Nidhi , Ji Fei , Guo Yuming , Herold Nicholas , Green Donna , Di Virgilio Giovanni , Beyer Kathleen , Riley Matthew L , Perkins-Kirkpatrick Sarah
Published: May 2022

Heatwaves are Australia’s deadliest natural hazard. Anthropogenic climate change has increased the intensity, frequency and duration of heatwaves over Australia in the past several decades and these trends are projected to worsen in the future. Despite the strong knowledge of heatwave characteristics and their projected changes, there remains a gap in understanding how the Australian population will be exposed to future heatwaves. This study estimates changes in future exposure to heatwaves over Australia. We find that both for continental Australia and its capital cities, the trends in exposure are not projected to increase, but accelerate in the future. For RCP4.5-SSP2 and RCP8.5-SSP5 scenarios, the mean exposure to heatwaves in Australia is projected to increase by ∼29 and ∼42 times by the end of 21st century. Sydney, Melbourne, and Adelaide are the major cities where the population is most exposed to future heatwaves, with this exposure projected to increase by 52, 61, and 56 times respectively under the RCP8.5-SSP5 scenario. The results demonstrate that anthropogenic climate change is the key contributor (over 95%) in enhancing future heatwave exposure and population change on its own plays a relatively minor role (less than 5%). The results of this study are crucial for planning where adaptation measures might be necessary to protect large group of vulnerable Australians to future heatwave exposure.
Response of rice phenology to climate warming weakened across China during 1981–2018: did climatic or anthropogenic factors play a role?
Authors: Zhang Liangliang , Zhang Zhao , Zhang Jing , Luo Yuchuan , Tao Fulu
Published: May 2022

Climate warming has substantially shifted plant phenology, which alters the length of growing season and consequently affects plant productivity. Recent studies showed a stalled or reversed impact of climate change on vegetation phenology since 1998, as well as an asymmetric warming effect. However, how field crop phenology responded to the recent climate warming and the asymmetric warming remains unknown. In addition, the relative roles of climate change, sowing date and cultivars shifts in the spatiotemporal changes of crop phenology at different regions need to be better understood. Here, using the latest 9,393 phenological records at 249 agro-meteorological stations across China over 1981–2018, we critically investigated the spatiotemporal dynamics of rice phenology and disentangled the effects of different drivers by exploiting the physiological relationship between crop phenology and thermal accumulation. The results showed that length of growing period (GP) increased by 3.24 ± 0.15 days/decade for single rice, 1.90 ± 0.22 days/decade for early rice and 0.47 ± 0.14 days/decade for late rice. Although climate warming during rice GP did not slow down, the trends in rice GP and the correlations between GP and temperature decreased generally from 1981–1999 to 2000–2018. The weakened phenological response to climate change was mainly caused by agronomic managements, especially cultivar shifts. Climate warming shortened GP by 0.84 ± 1.80, 1.23 ± 0.77, and 1.29 ± 1.24 days/decade for single rice, early rice and late rice, respectively. However, cultivar shifts prolonged it respectively by 3.28 ± 3.68, 2.15 ± 2.38, and 2.31 ± 3.36 days/decade, totally offsetting the negative effects of climate warming. Rice responded to daytime and night-time warming differently with night-time temperature affecting GPs more. Our study provided new insights that rice phenology responded to night-time warming more than daytime warming across China however the response to climate warming weakened, and cultivar shifts outweighed climate change in affecting rice phenology.
Evaluation of site-specific methylation of the CMV promoter and its role in CHO cell productivity of a recombinant monoclonal antibody
Authors: Dahodwala Hussain , Amenyah Sophia D , Nicoletti Sarah , Henry Matthew N , Lees-Murdock Diane J , Sharfstein Susan T
Published: May 2022

We previously demonstrated that increased monoclonal antibody productivity in dihydrofolate reductase (DHFR)-amplified CHO cells correlates with phosphorylated transcription factor-cytomegalovirus (CMV) promoter interactions. In this article, we extend the characterization to include CMV promoter methylation and its influence on NFκB and CREB1 transcription factor binding to the CMV promoter in two families of DHFR-amplified CHO cell lines. CMV promoter methylation was determined using bisulfite sequencing. To overcome Sanger-sequencing limitations due to high CG bias and multiple transgenes copies, pyrosequencing was used to determine the frequency of methylated cytosines in regions proximal to and containing the NFκB and CREB1 transcription-factor consensus binding sites. Chromatin immunoprecipitation was performed to interrogate transcription factor–DNA interactions. Antibodies to CREB1 and NFκB were used to immunoprecipitate formaldehyde-crosslinked protein-DNA fractions, followed by reverse transcription quantitative real-time polymerase chain reaction to quantitate the number of copies of CMV-promoter DNA bound to the various transcription factors. The relative unmethylated fraction at the CREB1 and NFκB consensus binding sites determined by pyrosequencing was correlated with transcription factor binding as determined by chromatin immunoprecipitation. Azacytidine treatment reduced methylation in all treated samples, though not at all methylation sites, while increasing transcription. Distinct promoter methylation patterns arise upon clonal selection in different families of cell lines. In both cell line families, increased methylation was observed upon amplification. In one family, the NFκB binding-site methylation was accompanied by increased CREB1 interaction with the promoter. In the other cell line family, lower methylation frequency at the NFκB consensus binding site was accompanied by more NFκB recruitment to the promoter region.
Assessing the Development of L2 Speaking Skills in Inside-School and Outside-School Settings Through Growth Modelling
Authors: Vandommele Goedele , Van Gorp Koen , Van den Branden Kris , De Maeyer Sven
Published: May 2022

This study investigates the differential effects of a task-based inside-school intervention and an outside-school project intervention on the development of speaking skills of 56 beginner second language (L2)-learners. The study extends previous research by looking at development across multiple occasions instead of two (i.e., a pretest and posttest), and by assessing speaking development by means of a non-intrusive task eliciting an informal conversation, rather than a formal test. To measure students’ development of Dutch speaking skills, syntactic complexity, lexical diversity, accuracy, fluency, and communicative effectiveness were assessed. Multilevel analyses revealed differential effects for both interventions. The task-based intervention inside school led to significant positive development of communicative effectiveness and syntactic complexity measured by length and subordination, but also to more breakdowns in fluency. The outside-school project intervention, however, did not result in any significant speaking development. The findings demonstrate the learning potential of a task-based inside-school intervention for developing various aspects of informal speaking skills, except for fluency. From a methodological perspective, this study illustrates the complexity of test and measure selection when assessing L2 speaking development.
International Prosecutors Acting before National Courts?: The Rome Statute System and the Ultimate Approach to Positive Complementarity
Authors: Wierczyńska Karolina
Published: May 2022

The paper discusses whether it is possible to install an international prosecutor before domestic courts to prosecute international crimes. As the “future of international law is domestic” the paper analyzes the question of possible development of the international criminal justice system, suggesting the ultimate approach to positive complementarity which includes international prosecutors acting before national courts. It begins with analyzing the concept of positive complementarity and its possible interpretations, arguing that there are no compelling policy reasons against reinterpreting the idea in order to allow an international prosecutor to act before national courts. Subsequently it briefly presents the first installments of such institutions and focuses on the challenges connected with providing such a scenario in a future.
Ensemble of opinion dynamics models to understand the role of the undecided about vaccines
Authors: Lenti Jacopo , Ruffo Giancarlo
Published: May 2022

In the last years, vaccines debate has attracted the attention of all the social media, with an outstanding increase during COVID-19 vaccination campaigns. The topic has created at least two opposing factions, pro- and anti-vaccines, that have conflicting and incompatible narratives. However, a not negligible fraction of the population has an unclear position, as many citizens feel confused by the vast amount of information coming from both sides in the online social network. The engagement of the undecided population by the two parties has a key role in the success of the vaccination campaigns. In this article, we present three models used to describe the recruitment of the undecided population by pro-vax and no-vax factions in a three-states context. Starting from real-world data of Facebook pages previously labelled as pro-, anti-vaccines or neutral, we describe and compare three opinion dynamics models that catch different behaviours of the undecided population. The first one is a variation of the SIS model, where undecided position is considered an indifferent position, including users not interested in the discussion. Neutrals can be ‘infected’ by one of the two extreme factions, joining their side, and they ‘recover’ when they lose interest in the debate and go back to neutrality. The second model studied is a Voters model with three parties: neutral pages represent a centrist position. They lean on their original ideas, that are different from both the other parties. The last is the Bilingual model adapted to the vaccination debate: it describes a context where neutral individuals are in agreement with both pro- and anti-vax factions, with a position of compromise between the extremes (‘bilingualism’). If they have a one-sided neighbourhood, the necessity (or the convenience) to agree with both parties comes out, and bi-linguists can become mono-linguists. Our results depicts an agreement between the three models: anti-vax opinion propagates more than pro-vax, thanks to an initial strategic position in the online social network (even if they start with a smaller population). While most of the pro-vaccines nodes are segregated in their own communities, no-vaccines ones are entangled at the core of the network, where the majority of the undecided population is located. In the last section, we propose and compare some policies that could be applied to the network to prevent anti-vax overcome: they lead us to conclude that censoring strategies are not effective, as well as segregating scenarios based on unfollowing decisions, while the addition of links in the network favours the containment of the pro-vax domain, reducing the distance between pro-vaxxers and undecided population.
An antiplatelet response gene expression signature is associated with bleeding
Authors: Friede Kevin A , Myers Rachel A , Gales Jordan , Zhbannikov Ilya , Ortel Thomas L , Shah Svati H , Kraus William E , Ginsburg Geoffrey S , Voora Deepak
Published: May 2022

Aims

Gene expression biosignatures may hold promise to individualize antiplatelet therapy in conjunction with current guidelines and risk scores. The Aspirin Response Signature (ARS) score is comprised of a weighted sum of correlated, pro-thrombotic gene transcripts measured in whole blood. In prior work where volunteers were exposed to aspirin 325 mg daily, higher ARS score was associated with lower platelet function; separately, in a clinical cohort of patients, higher ARS scores were associated with increased risk of adverse cardiovascular events. To better understand this apparent paradox, we measured ARS gene expression and score in volunteers to determine aspirin dose–response and ticagrelor relationships with ARS score and separately in patients to assess whether ARS is associated with incident bleeding.

Methods and results

Blood samples were collected from volunteers (N = 188) who were exposed to 4 weeks of daily aspirin 81 mg, daily aspirin 325 mg, and/or twice-daily ticagrelor 90 mg. ARS scores were calculated from whole blood RNA qPCR, and platelet function and protein expression were assessed in platelet-rich plasma. In mixed linear regression models, aspirin 81 mg exposure was not associated with changes in ARS gene expression or score. Aspirin 325 mg exposure resulted in a 6.0% increase in ARS gene expression (P = 7.5 × 10−9 vs. baseline, P = 2.1 × 10−4 vs. aspirin 81 mg) and an increase in expression of platelet proteins corresponding to ARS genes. Ticagrelor exposure resulted in a 30.7% increase in ARS gene expression (P < 1 × 10−10 vs. baseline and each aspirin dose) and ARS score (P = 7.0 × 10−7 vs. baseline, P = 3.6 × 10−6 and 5.59 × 10−4 vs. aspirin 81 and 325 mg, respectively). Increases in ARS gene expression or score were associated with the magnitude of platelet inhibition across agents. To assess the association between ARS scores and incident bleeding, ARS scores were calculated in patients undergoing cardiac catheterization (N = 1421), of whom 25.4% experienced bleeding events over a median 6.2 years of follow-up. In a Cox model adjusting for demographics and baseline antithrombotic medication use, patients with ARS scores above the median had a higher risk of incident bleeding [hazard ratio 1.26 (95% CI 1.01–1.56), P = 0.038].

Conclusions

The ARS is an Antiplatelet Response Signature that increases in response to greater platelet inhibition due to antiplatelet therapy and may represent a homeostatic mechanism to prevent bleeding. ARS scores could inform future strategies to prevent bleeding while maintaining antiplatelet therapy’s benefit of ischaemic cardiovascular event protection.
SKIOME Project: a curated collection of skin microbiome datasets enriched with study-related metadata
Authors: Agostinetto Giulia , Bozzi Davide , Porro Danilo , Casiraghi Maurizio , Labra Massimo , Bruno Antonia
Published: May 2022

Large amounts of data from microbiome-related studies have been (and are currently being) deposited on international public databases. These datasets represent a valuable resource for the microbiome research community and could serve future researchers interested in integrating multiple datasets into powerful meta-analyses. However, this huge amount of data lacks harmonization and it is far from being completely exploited in its full potential to build a foundation that places microbiome research at the nexus of many subdisciplines within and beyond biology. Thus, it urges the need for data accessibility and reusability, according to findable, accessible, interoperable and reusable (FAIR) principles, as supported by National Microbiome Data Collaborative and FAIR Microbiome. To tackle the challenge of accelerating discovery and advances in skin microbiome research, we collected, integrated and organized existing microbiome data resources from human skin 16S rRNA amplicon-sequencing experiments. We generated a comprehensive collection of datasets, enriched in metadata, and organized this information into data frames ready to be integrated into microbiome research projects and advanced post-processing analyses, such as data science applications (e.g. machine learning). Furthermore, we have created a data retrieval and curation framework built on three different stages to maximize the retrieval of datasets and metadata associated with them. Lastly, we highlighted some caveats regarding metadata retrieval and suggested ways to improve future metadata submissions. Overall, our work resulted in a curated skin microbiome datasets collection accompanied by a state-of-the-art analysis of the last 10 years of the skin microbiome field.

Database URL:  https://github.com/giuliaago/SKIOMEMetadataRetrieval
Artificial intelligence—electrocardiography to detect atrial fibrillation: trend of probability before and after the first episode
Authors: Christopoulos Georgios , Attia Zachi I , Van Houten Holly K , Yao Xiaoxi , Carter Rickey E , Lopez-Jimenez Francisco , Kapa Suraj , Noseworthy Peter A , Friedman Paul A
Published: May 2022

Aims

Artificial intelligence (AI) enabled electrocardiography (ECG) can detect latent atrial fibrillation (AF) in patients with sinus rhythm (SR). However, the change of AI-ECG probability before and after the first AF episode is not well characterized. We sought to characterize the temporal trend of AI-ECG AF probability around the first episode of AF.

Methods and results

We retrospectively studied adults who had at least one ECG in SR prior to an ECG that documented AF. An AI network calculated the AF probability from ECGs during SR (positive defined >8.7%, based on optimal sensitivity and specificity). The AI-ECG probability was reported prior to and after the first episode of AF and stratified by age and CHA2DS2-VASc score. Mixed effect models were used to assess the rate of change between time points. A total of 59 212 patients with 544 330 ECGs prior to AF and 413 486 ECGs after AF were included. The mean time between the first positive AI-ECG and first AF was 5.4 ± 5.7 years. The mean AI-ECG probability was 19.8% 2–5 years prior to AF, 23.6% 1–2 years prior to AF, 34.0% 0–3 months prior to AF, 40.9% 0–3 months after AF, 35.2% 1–2 years after AF, and 42.2% 2–5 years after AF (P < 0.001). The rate of increase prior to AF was higher for age >50 years CHA2DS2-VASc score ≥4.

Conclusion

The AI-ECG probability progressively increases with time prior to the first AF episode, transiently decreases 1–2 years following AF and continues to increase thereafter.
Robotic-assisted thoracoscopic surgery demonstrates a lower rate of conversion to thoracotomy than video-assisted thoracoscopic surgery for complex lobectomies
Authors: Baig Mirza Zain , Razi Syed S , Agyabeng-Dadzie Kojo , Stroever Stephanie , Muslim Zaid , Weber Joanna , Herrera Luis J , Bhora Faiz Y
Published: May 2022

OBJECTIVES

Locally advanced lung cancers present a significant challenge to minimally invasive thoracic surgeons. An increasing number of centres have adopted robotic-assisted thoracoscopic surgeries for these complex operations. In this study, we compare surgical margins achieved, conversion rates to thoracotomy, perioperative mortality and 30-day readmission rates for robotic and video-assisted thoracoscopic surgery (VATS) lobectomy for locally advanced lung cancers.

METHODS

Using the National Cancer Database, we identified patients with non-small-cell lung cancer who received neoadjuvant chemotherapy/radiotherapy, had clinical N1/N2 disease or in the absence of these 2 features had a tumour >5 cm treated with either robotic or VATS lobectomy between 2010 and 2016. Perioperative outcomes and conversion rates were compared between robotic and VATS lobectomy.

RESULTS

A total of 9512 patients met our inclusion criteria with 2123 (22.3%) treated with robotic lobectomy and 7389 (77.7%) treated with VATS lobectomy. Comparable R0 resections, 30- and 90-day mortality and 30-day readmission rates were observed for robotic and VATS lobectomy while a higher rate of conversion to thoracotomy was observed for VATS (aOR = 1.99, 95% confidence interval = 1.65, 2.39, P < 0.001).

CONCLUSIONS

Our analysis of the National Cancer Database suggests that robotic lobectomy for complex lung resections achieves similar perioperative outcomes and R0 resections as VATS lobectomy with the exception of a lower rate of conversion to thoracotomy.
Characteristics and natural history of early-stage cardiac transthyretin amyloidosis
Authors: Law Steven , Bezard Melanie , Petrie Aviva , Chacko Liza , Cohen Oliver C , Ravichandran Sriram , Ogunbiyi Olabisi , Kharoubi Mounira , Ganeshananthan Sashiananthan , Ganeshananthan Sharmananthan , Gilbertson Janet A , Rowczenio Dorota , Wechalekar Ashutosh , Martinez-Naharro Ana , Lachmann Helen J , Whelan Carol J , Hutt David F , Hawkins Philip N , Damy Thibaud , Fontana Marianna , Gillmore Julian D
Published: May 2022

Aims

Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly diagnosed at an early stage of the disease natural history, defined as National Amyloidosis Centre (NAC) ATTR Stage I. The natural history of early-stage ATTR-CM remains poorly characterized.

Methods and results

A retrospective multi-centre observational study of 879 patients with ATTR-CM, either wild-type TTR genotype or carrying the p.V142I TTR variant, and NAC ATTR Stage I biomarkers at the time of diagnosis who did not receive disease-modifying therapy for amyloidosis. Disease characteristics at diagnosis that were independently associated with mortality by Cox regression analysis were N-terminal pro-B-type natriuretic peptide (NT-proBNP), TTR genotype, and troponin T. Patients were categorized into NAC ATTR Stage Ia, defined as a furosemide equivalent diuretic requirement of <0.75 mg/kg and an NT-proBNP ≤500 ng/L or ≤1000 ng/L in the presence of atrial fibrillation, and NAC ATTR Stage Ib comprising all remaining Stage I patients. Median estimated survival among the 88% NAC ATTR Stage Ib patients was 75 (95% CI 57–93) months compared with >100 months in the 12% with Stage Ia disease [hazard ratio for death 5.06 (95% confidence interval 1.23–20.87); P = 0.025] despite significant cardiovascular morbidity at the time of diagnosis which increased during follow-up, including among patients diagnosed in NAC ATTR Stage Ia. Estimated survival among UK NAC ATTR Stage Ia patients was comparable to UK general population controls (P = 0.297).

Conclusion

Patients with NAC ATTR Stage I ATTR-CM can be further stratified according to NT-proBNP concentration and diuretic requirement at diagnosis. Patients with Stage Ia ATTR-CM have significant cardiovascular morbidity despite good short- and mid-term survival.
Circulating micro-RNAs Differentially Expressed in Korean Alzheimer’s Patients With Brain Aβ Accumulation Activate Amyloidogenesis
Authors: Mankhong Sakulrat , Kim Sujin , Moon Sohee , Choi Seong-Hye , Kwak Hyo-Bum , Park Dong-Ho , Shah Pratik , Lee Phil Hyu , Yang Seong Wook , Kang Ju-Hee
Published: May 2022

Background

Roles for extracellular vesicles (EVs) enriched with micro-RNAs (miRNAs) have been proposed in Alzheimer’s disease (AD) pathogenesis, leading to the discovery of blood miRNAs as AD biomarkers. However, the diagnostic utility of specific miRNAs is not consistent. This study aimed to discover blood miRNAs that are differentially expressed in Korean AD patients, evaluate their clinical performance, and investigate their role in amyloidogenesis.

Methods

We discovered miRNAs differentially expressed in AD (N = 8) from cognitively normal participants (CN, N = 7) or Parkinson’s disease (PD) patients (N = 8). We evaluated the clinical performance of these miRNAs in plasma of subgroup (N = 99) and in plasma EVs isolated from the total cohort (N = 251). The effects of miRNAs on amyloidogenesis and on the regulation of their target genes were investigated in vitro.

Results

Among 17 upregulated and one downregulated miRNAs in AD (>twofold), miR-122-5p, miR-210-3p, and miR-590-5p were differentially expressed compared with CN or PD. However, the diagnostic performance of the selected plasma or EV miRNAs in total participants were limited (area under the curve < 0.8). Nevertheless, levels of 3 miRNAs in plasma or plasma EVs of participants who were amyloid positron emission tomography (Aβ-PET) positive were significantly higher than those from the Aβ-PET negative participants (p < .05). The selected miRNAs induced Aβ production (p < .05) through activation of β-cleavage of amyloid precursor protein (CTF-β; p < .01), and downregulated their target genes (ADAM metallopeptidase domain 10, Brain-derived neurotrophic factor, and Jagged canonical notch ligand 1; p < .05), which was further supported by pathway enrichment analysis of target genes of the miRNAs.

Conclusion

In conclusion, despite of the limited diagnostic utility of selected miRNAs as plasma or plasma EV biomarkers, the discovered miRNAs may play a role in amyloidogenesis during AD onset and progression.
Nursing Home Palliative Care During the Pandemic: Directions for the Future
Authors: Ninteau Kacy , Bishop Christine E
Published: May 2022

Background and Objectives

Palliative care addresses physical, emotional, psychological, and spiritual suffering that accompanies serious illness. Emphasis on symptom management and goals of care is especially valuable for seriously ill nursing home residents. We investigated barriers to nursing home palliative care provision highlighted by the coronavirus disease 2019 (COVID-19) pandemic and the solutions nursing home staff used to provide care in the face of those barriers.

Research Design and Methods

For this descriptive qualitative study, seven Massachusetts nursing home directors of nursing were interviewed remotely about palliative care provision before and during the COVID-19 pandemic. Interview data were analyzed using thematic analysis.

Results

Before the pandemic, palliative care was delivered primarily by nursing home staff depending on formal and informal consultations from palliative care specialists affiliated with hospice providers. When COVID-19 lockdowns precluded these consultations, nursing staff did their best to provide palliative care, but were often overwhelmed by shortfalls in resources, resident decline brought on by isolation and COVID-19 itself, and a sense that their expertise was lacking. Advance care planning conversations focused on hospitalization decisions and options for care given resource constraints. Nevertheless, nursing staff discovered previously untapped capacity to provide palliative care on-site as part of standard care, building trust of residents and families.

Discussion and Implications

Nursing staff rose to the palliative care challenge during the COVID-19 pandemic, albeit with great effort. Consistent with prepandemic analysis, we conclude that nursing home payment and quality standards should support development of in-house staff capacity to deliver palliative care while expanding access to the formal consultations and family involvement that were restricted by the pandemic. Future research should be directed to evaluating initiatives that pursue these aims.
Inequalities in Health Impact of Alternative Reimbursement Pathways for Nirsevimab in the United States
Authors: Gomez Gabriela B , Nelson Christopher B , Rizzo Christopher , Shepard Donald S , Chaves Sandra S
Published: May 2022

The target populations and financing mechanisms for a new health technology may affect health inequalities in access and impact. We projected the distributional consequences of introducing nirsevimab for prevention of respiratory syncytial virus in a US birth cohort of infants through alternative reimbursement pathway scenarios. Using the RSV immunization impact model, we estimated that a vaccine-like reimbursement pathway would cover 32% more infants than a pharmaceutical pathway. The vaccine pathway would avert 30% more hospitalizations and 39% more emergency room visits overall, and 44% and 44%, respectively, in publicly insured infants. The vaccine pathway would benefit infants from poorer households.
Phenomics data processing: extracting dose–response curve parameters from high-resolution temperature courses and repeated field-based wheat height measurements
Authors: Roth Lukas , Piepho Hans-Peter , Hund Andreas
Published: May 2022

Temperature is a main driver of plant growth and development. New phenotyping tools enable quantifying the temperature response of hundreds of genotypes. Yet, for field-derived data, temperature response modelling bears flaws and pitfalls concerning the interpretation of derived parameters. In this study, climate data from five growing seasons with differing temperature distributions served as starting point for a growth simulation of wheat stem elongation, based on a four-parametric temperature response function (Wang–Engel) including all cardinal temperatures. In a novel approach, we re-extracted dose–responses from the simulation by combining high-resolution (hours) temperature courses with low-resolution (days) height data. The collection of such data is common in field phenotyping platforms. To take advantage of the lack of supra-optimal temperatures during the stem elongation, simpler (linear and asymptotic) models to predict temperature response parameters were investigated. The asymptotic model extracted the base temperature of growth and the maximum absolute growth rate with high precision, whereas simpler, linear models failed to do so. Additionally, the asymptotic model provided a proxy estimate for the optimum temperature. However, when including seasonally changing cardinal temperatures, the prediction accuracy of the asymptotic model was strongly reduced. In a field study with three winter wheat varieties, significant differences were found for all three asymptotic dose–response curve parameters. We conclude that the asymptotic model based on high-resolution temperature courses is suitable to extract meaningful parameters from field-based data.
The Utility of Myositis Specific Antibodies in Clinical Practice
Authors: Biddle Kathryn , Taylor Matthew D , Linstead Sarah E , Kiely Patrick D W
Published: May 2022

Background

Fifteen myositis-specific antibodies have been described and characterized over the past 40 years. Approximately two thirds of patients with idiopathic inflammatory myositis have a myositis-specific antibody and only rarely more than one. Assays to detect them are now widely available within clinical practice.

Content

We describe the original description and clinical phenotype of the myositis-specific antibodies, forming the antisynthetase syndrome group, anti-MDA-5 and rapidly progressive interstitial lung disease, anti-SRP/HMGCR and necrotizing myositis, anti-TIF-1γ/NXP-2 and malignancy, anti-SAE and esophageal disease, and anti-Mi-2 and classic dermatomyositis skin disease.

Clinical practice is likely to be refined, with diagnosis and classification of the idiopathic inflammatory myositides based primarily on myositis-specific antibody, rather than directed by muscle histology or the broader clinical characteristics of polymyositis and dermatomyositis. All patients newly presenting with idiopathic inflammatory myositis should be routinely screened for myositis-specific antibodies. A positive result will usefully provide diagnostic and prognostic information, guide selection of therapy, and prompt surveillance for potential organ involvement and other features, such as cancer, throughout the disease course.
Built by epidemiologists for epidemiologists: an internal COVID-19 dashboard for real-time situational awareness in New York City
Authors: Ngai Stephanie , Sell Jessica , Baig Samia , Iqbal Maryam , Eddy Meredith , Culp Gretchen , Montesano Matthew , McGibbon Emily , Johnson Kimberly , Devinney Katelynn , Baumgartner Jennifer , Huynh Mary , Mathes Robert , Van Wye Gretchen , Fine Annie D , Thompson Corinne N
Published: May 2022

Objective

New York City (NYC) experienced a large first wave of coronavirus disease 2019 (COVID-19) in the spring of 2020, but the Health Department lacked tools to easily visualize and analyze incoming surveillance data to inform response activities. To streamline ongoing surveillance, a group of infectious disease epidemiologists built an interactive dashboard using open-source software to monitor demographic, spatial, and temporal trends in COVID-19 epidemiology in NYC in near real-time for internal use by other surveillance and epidemiology experts.

Materials and methods

Existing surveillance databases and systems were leveraged to create daily analytic datasets of COVID-19 case and testing information, aggregated by week and key demographics. The dashboard was developed iteratively using R, and includes interactive graphs, tables, and maps summarizing recent COVID-19 epidemiologic trends. Additional data and interactive features were incorporated to provide further information on the spread of COVID-19 in NYC.

Results

The dashboard allows key staff to quickly review situational data, identify concerning trends, and easily maintain granular situational awareness of COVID-19 epidemiology in NYC.

Discussion

The dashboard is used to inform weekly surveillance summaries and alleviated the burden of manual report production on infectious disease epidemiologists. The system was built by and for epidemiologists, which is critical to its utility and functionality. Interactivity allows users to understand broad and granular data, and flexibility in dashboard development means new metrics and visualizations can be developed as needed.

Conclusions

Additional investment and development of public health informatics tools, along with standardized frameworks for local health jurisdictions to analyze and visualize data in emergencies, are warranted.
A case of post-operative stenosis caused by colonic ischemia after low anterior resection for rectal cancer, followed by delayed colo-anal anastomosis
Authors: Uchiyama Shuichiro , Ikeda Naotaka , Oyama Tomohiro , Eguchi Mayumi , Ito Ayaka , Sato Rikiya , Toyosaki Ryoichi , Kitazono Masaki , Suenaga Toyokuni
Published: May 2022

Cases of delayed colo-anal anastomosis (DCAA) are currently reported instead of the colo-anal anastomosis with a protective loop ileostomy for rectal cancer. Post-operative colonic ischemia is considered as one of the serious complications of colorectal resection. Although indication of DCAA should be carefully selected, we experienced a case of post-operative stenosis caused by colonic ischemia after low anterior resection for rectal cancer, followed by this procedure.
Hamiltonian Monte Carlo reconstruction from peculiar velocities
Authors: Valade Aurélien , Hoffman Yehuda , Libeskind Noam I , Graziani Romain
Published: May 2022

The problem of the reconstruction of the large-scale density and velocity fields from peculiar velocity surveys is addressed here within a Bayesian framework by means of Hamiltonian Monte Carlo (HMC) sampling. The HAmiltonian Monte carlo reconstruction of the Local EnvironmenT (hamlet) algorithm is designed to reconstruct the linear large-scale density and velocity fields in conjunction with the undoing of lognormal bias in the derived distances and velocities of peculiar velocity surveys, such as the Cosmicflows (CF) data. The hamlet code has been tested against CF mock catalogues consisting of up to 3 × 104 data points with mock errors akin to those of the Cosmicflows-3 (CF3) data, within the framework of the Lambda cold dark matter standard model of cosmology. The hamlet code outperforms previous applications of Gibbs sampling Markov chain Monte Carlo reconstruction from the CF3 data by two to four orders of magnitude in CPU time. The gain in performance is due to the inherent higher efficiency of the HMC algorithm and due to parallel computing on GPUs rather than CPUs. This gain will enable an increase in the reconstruction of the large-scale structure from the upcoming CF4 data and the setting of constrained initial conditions for cosmological high-resolution simulations.
Semi-analytic spectral fitting: simultaneously modelling the mass accumulation and chemical evolution in MaNGA spiral galaxies
Authors: Zhou Shuang , Merrifield Michael , Aragón-Salamanca Alfonso
Published: May 2022

We develop a novel semi-analytic spectral fitting approach to quantify the star-formation histories (SFHs) and chemical enrichment histories (ChEHs) of individual galaxies. We construct simple yet general chemical evolution models that account for gas inflow and outflow processes as well as star formation, to investigate the evolution of merger-free star-forming systems. These models are fitted directly to galaxies’ absorption-line spectra, while their emission lines are used to constrain current gas phase metallicity and star formation rate. We apply this method to spiral galaxies selected from the SDSS-IV MaNGA survey. By fitting the co-added absorption-line spectra for each galaxy, and using the emission-line constraints on present-day metallicity and star formation, we reconstruct both the SFHs and the ChEHs for all objects in the sample. We can use these reconstructions to obtain archaeological measures of derived correlations such as the mass–metallicity relation at any redshift, which compare favourably with direct observations. We find that both the SFHs and ChEHs have strong mass dependence: massive galaxies accumulate their stellar masses and become enriched earlier. This mass dependence causes the observed flattening of the mass–metallicity relation at lower redshifts. The model also reproduces the observed gas-to-stellar mass ratio and its mass dependence. Moreover, we are able to determine that more massive galaxies have earlier gas infall times and shorter infall time-scales, and that the early chemical enrichment of low-mass galaxies is suppressed by strong outflows, while outflows are not very significant in massive galaxies.
Unveiling the nature of the unidentified gamma-ray sources 4FGL J1908.6+0915e, HESS J1907+089/HOTS J1907+091, and 3HWC J1907+085 in the sky region of the magnetar SGR 1900+14
Authors: Hnatyk B , Hnatyk R , Zhdanov V , Voitsekhovskyi V
Published: May 2022

Supernova remnants (SNRs), star formation regions (SFRs), and pulsar wind nebulae (PWNe) are prime candidates for Galactic PeVatrons. The non-thermal high-energy (HE, ε > 100 MeV) and very high-energy (VHE, ε > 100 GeV) γ-ray emission from these sources should be a promising manifestation of acceleration processes. We investigate the possibility to explain the HE and VHE γ-ray emission from the sky region of the magnetar SGR 1900+14 as a signature of cosmic rays accelerated in above-mentioned sources. To this end, we simulate the γ-ray emission from the extended Fermi-LAT HE source 4FGL J1908.6+0915e, the extended VHE H.E.S.S. source candidate HOTS J1907+091, and the point-like HAWC TeV source 3HWC J1907+085, which are spatially coincident with the SNR G42.8+0.6, the magnetar SGR 1900+14, and the star-forming region W49A. The simulations are performed within the hadronic and leptonic models. We show that the observed γ-ray emission from the region of the magnetar SGR 1900+14 can, in principle, include contributions of different intensities from all three types of (potentially confused) sources. The considered in detail cases of a magnetar-connected but still undetected SNR and a PWN are the most promising ones, but with a serious requirement on the energy reserve of radiated CR particles – of the order of $10^{51}d_{\textrm {10kpc}}^{2}$ erg for sources at a distance of d ∼ 10 kpc. Such energy reserve can be provided by the magnetar-related hypernova and/or magnetar wind nebula remnant created by the newborn millisecond magnetar with the large supply of rotational energy Erot ∼ 1052 erg.