bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel findings of an old algorithm: PVC response “Atrial Pace’’ initiates atrial arrhythmias in Abbott ICD and CRT‐D devices
Authors: Sane Markus , Marjamaa Annukka , Kuusisto Jouni , Raatikainen Pekka , Karvonen Jarkko 
Published: November 2022

AbstractBackgroundMany algorithms have been developed to ensure the safety and accuracy of cardiac implantable electric devices (CIED). A specific algorithm designed to prevent pacemaker induced tachycardia (PMT) after a premature ventricular complex (PVC response) is available in all Abbott (former St. Jude Medical) CIED. However, a few case reports suggest that this algorithm may be proarrhythmic when programmed to Atrial Pace (A‐Pace on PVC).MethodsWe analyzed the data of all (n = 333) Abbot implantable cardioverter defibrillator (ICD) and cardiac resynchronization defibrillator (CRT‐D) devices followed remote using the Merlin.net Patient Care Network in our institute in 2020. Status of the PVC response algorithm A‐Pace on PVC or Off was collected, and all atrial mode switch (AMS) episodes longer than 30 s were thoroughly evaluated. Data on clinical characteristics of the patients was collect from the electronic patient records.ResultsA total of 173 patients had A‐Pace on PVC and twenty‐five of them (14%) had at least one atrial high rate episode (AHRE) >30 s (AHRE) triggered by the action of this algorithm. The median PVC count was higher in patients who had algorithm triggered AHRE than in those with no algorithm‐triggered AHRE (1.7% [IQR 0–3.2] vs. 0% [IQR 0–1.1], p < .0001). The major clinical characteristics were comparable in the two groups.ConclusionThe A‐Pace on PVC setting was frequently used in our patients. Our study shows that a considerable number of patients had at least one AHRE triggered by the algorithm. The use of this algorithm should be carefully reconsidered.
CRISPR‐induced miRNA156‐recognition element mutations in TaSPL13 improve multiple agronomic traits in wheat
Authors: Gupta Ajay , Hua Lei , Zhang Zhengzhi , Yang Bing , Li Wanlong 
Published: November 2022

SummaryIncrease in grain yield is always a major objective of wheat genetic improvement. The SQUAMOSA promoter‐binding protein‐like (SPL) genes, coding for a small family of diverse plant‐specific transcription factors, represent important targets for improving grain yield and other major agronomic traits in rice. The function of the SPL genes in wheat remains to be investigated in this respect. In this study, we identified 56 wheat orthologues of rice SPL genes belonging to 19 homoeologous groups. Like in rice, nine orthologous TaSPL genes harbour the microRNA156 recognition elements (MRE) in their last exons except for TaSPL13, which harbour the MRE in its 3′‐untranslated region (3′UTR). We modified the MRE of TaSPL13 using CRISPR‐Cas9 and generated 12 mutations in the three homoeologous genes. As expected, the MRE mutations led to an approximately two‐fold increase in the TaSPL13 mutant transcripts. The phenotypic evaluation showed that the MRE mutations in TaSPL13 resulted in a decrease in flowering time, tiller number, and plant height, and a concomitantly increase in grain size and number. The results show that the TaSPL13 mutants exhibit a combination of different phenotypes observed in Arabidopsis AtSPL3/4/5 mutants and rice OsSPL13/14/16 mutants and hold great potential in improving wheat yield by simultaneously increasing grain size and number and by refining plant architecture. The novel TaSPL13 mutations generated can be utilized in wheat breeding programmes to improve these agronomic traits.
A novel plant‐made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS‐CoV‐2 Omicron variant
Authors: Jugler Collin , Sun Haiyan , Nguyen Katherine , Palt Roman , Felder Mitchell , Steinkellner Herta , Chen Qiang 
Published: November 2022

SummaryThis study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan‐Hu‐1 RBD of SARS‐CoV‐2. We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human‐like, highly homogenous N‐linked glycans that has potential to impart greater potency and safety as a therapeutic. The epitope of 11D7 was mapped by competitive binding with well‐characterized mAbs, suggesting that it is a Class 4 RBD‐binding mAb that binds to the RBD outside the ACE2 binding site. Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. Taken together, 11D7 is a unique mAb that neutralizes SARS‐CoV‐2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety‐friendly alternative platform for generating mAbs to address the evolving SARS‐CoV‐2 crisis.
Longitudinal utilization of systemic immunomodulators before and after dupilumab approval in children with atopic dermatitis
Authors: Anand Priyanka , Schneeweiss Sebastian , Mostaghimi Arash , Schneeweiss Maria C. 
Published: November 2022

AbstractIn our cohort study, we sought to describe the utilization patterns of systemic immunomodulators in children with atopic dermatitis (AD) and how utilization changed after approval of dupilumab, the first systemic drug approved for the treatment of AD. Using US nationwide claims data, we identified children with AD who initiated a systemic therapy (dupilumab, cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil) from March 2015 to February 2021 and used Sankey plots to describe patterns of starting, switching, and discontinuing these drugs. Dupilumab use among children increased from 19.4% before approval in children to 88.3% after approval in 2019–20. Adherence to dupilumab may suggest better tolerance and improved outcomes in children with AD.
Morphea after initiation of dupilumab in two pediatric atopic dermatitis patients
Authors: Wang Sonia , Berry Corbett T. , Treat James R. , Jen Melinda 
Published: November 2022

AbstractMorphea is a rare multifactorial autoimmune disorder characterized by a complex and dynamic interplay between Th1 and Th2 signaling. Active clinical trials are currently investigating the safety and efficacy of dupilumab for the treatment of primary morphea. Here, we present two cases of morphea that developed in pediatric atopic dermatitis patients treated with dupilumab. These findings may support a causal relationship between IL‐4 receptor blockade and the development of the early inflammatory phase of morphea.
The Playground Shade Index: A New Design Metric for Measuring Shade and Seasonal Ultraviolet Protection Characteristics of Parks and Playgrounds
Authors: Downs Nathan , Raj Nawin , Vanos Jennifer , Parisi Alfio V. , Butler Harry , Deo Ravinesh , Igoe Damien , Dexter Benjamin , Beckman‐Downs Melanie , Turner Joanna , Dekeyser Stijn 
Published: November 2022

AbstractCurrent shading strategies used to protect outdoor playgrounds from harmful solar radiation include the placement of artificial cloth weaves or permanent roofing over a playground site, planting trees in proximity to playground equipment, and using vegetation or surface texture variations to cool playground surfaces. How and where an artificial shade structure is placed or a tree is planted to maximize the shade protection over specific playground areas, requires careful assessment of local seasonal sun exposure patterns. The Playground Shade Index (PSI) is introduced here as a design metric to enable shade and solar ultraviolet exposure patterns to be derived in an outdoor space using conventional aerial views of suburban park maps. The implementation of the PSI is demonstrated by incorporating a machine learning design tool to classify the position of trees from an aerial image, thus enabling the mapping of seasonal shade and ultraviolet exposure patterns within an existing 7180 m2 parkland. This is achieved by modeling the relative position of the sun with respect to nearby buildings, shade structures, and the identified evergreen and deciduous tree species surrounding an outdoor playground.
Antifungal chemotherapies and immunotherapies for the future
Authors: Armstrong‐James Darius 
Published: November 2022

AbstractHuman fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic pathogens are capable of morphotype switching, they present unique challenges both for drug development and the immunological response. Whilst current antifungal therapies are limited to the orally available triazoles, intravenous echonocandins and polyenes, and flucytosine and terbinafine, there has been recent significant progress in the antifungal armamentorium with ibrexafungerp, a novel orally available terpanoid that inhibits 1,3‐beta‐D‐glucan‐approved by Food and Drug Administration in 2021, and fosmanogepix, an orally available pro‐drug of manogepix, which targets glycosylphosphatidylinositol‐anchored protein maturation entering Phase 3 studies for candidaemia. A number of further candidates are in development. There has been significant use of existing immunotherapies such as recombinant interferon‐γ and G‐CSF for fungal disease in immunocompromised patients, and there are emerging opportunities for monoclonal antibodies targeting TH2 inflammation. Omalizumab, an anti‐IgE monoclonal antibody in asthma, is now used routinely for the treatment of allergic bronchopulmonary aspergillosis, and further agents targeting IL‐4 and IL‐5 are being evaluated. In addition, T‐cell CAR therapy is showing early promise for fungal disease. Thus, we are likely to see rapid advances to our approach to the management of fungal disease in the near future.
Intercropping alleviated the phytotoxic effects of cinnamic acid on the root cell wall structural resistance of faba bean and reduced the occurrence of Fusarium wilt
Authors: Yang Wenhao , Li Yu , Zhao Qian , Guo Yuting , Dong Yan 
Published: November 2022

AbstractSoilborne Fusarium wilt is a key factor restricting the cultivation of faba bean. Intercropping faba bean and wheat effectively alleviate faba bean Fusarium wilt. This study analyzed the mechanism by which cinnamic acid promotes Fusarium wilt and the mechanism that enables intercropping alleviated Fusarium wilt. Faba beans were inoculated with Fusarium oxysporum f. sp. fabae (FOF), while the controls were not inoculated. Different concentrations of cinnamic acid were added to the inoculated plants to study the occurrence of Fusarium wilt, seedling growth, the activities of cell wall degradation enzyme (CWDESs) produced by FOF in the root, defense enzymes, total phenolics and lignin, levels of expression of the pathogenesis‐related genes (PRs) PR1, PR2, and PR10, and changes in the submicroscopic cell wall structure of the roots under monocropping and intercropping systems. Cinnamic acid increased the activities of CWDEs produced by FOF in the roots, increased the activities of phenylalanine ammonia lyase and polyphenol oxidase and the contents of total phenolics and lignin, and upregulated the levels of expression of PRs in the root, but it decreased the activity of peroxidase. Transmission electron microscopy (TEM) observations identified severe damage and disruption of the root cell walls, and numerous FOF mycelia entered the cytoplasm from the cell wall. The combination of these factors increased the occurrence of Fusarium wilt. The activities of CWDEs produced by FOF in the roots decreased by intercropping wheat with faba bean, which increased the resistance of the root cell walls to infection and decreased the Fusarium wilt.
An Unpublished Autograph Letter from Sir Philip Sidney to Carolus Clusius, 21 April 1576
Authors: Vozar Thomas Matthew 
Published: November 2022

AbstractOnly a decade ago Roger Kuin's The Correspondence of Sir Philip Sidney (2012) offered scholars for the first time a complete edition of Sidney's correspondence. Kuin modestly allowed room for new discoveries, in the hope that additional letters might be identified. This article introduces a previously unpublished autograph letter by Sidney, written in French, addressed on 21 April 1576 to Carolus Clusius or Charles de l'Écluse, an associate of Hubert Languet and a noted botanist then active in Vienna at the court of the Holy Roman Emperor Maximilian II. After briefly discussing the provenance of the manuscript I turn to its contents, situating the letter within the wider corpus of Sidney's extant correspondence, with reference to letters to and from Clusius and Languet in Kuin's edition, and analysing it within this context. The newly discovered letter, transcribed and translated in an appendix, is shown to offer important new evidence for Sidney's relationships with Clusius and Languet as well as his place in European intellectual culture more generally.
Handling shifts during an overnight sailing regatta: Comparison between sleep management strategies
Authors: Bruno Simone , Ceccanti Serena , Bazzani Andrea , d'Ascanio Paola , Frumento Paolo , Faraguna Ugo 
Published: November 2022

The study aims to investigate the association between different sleep management strategies and the final ranking during a one‐night sailing race. A large sample of 190 teams participating in the overnight sailing regatta (151 Miglia) were included in the study. The experimental design consisted of two surveys, administered one before the start of the race and the other after the arrival. The questionnaires provided general information on the sailboat, its crew, and the strategy adopted to manage sleep during the race. In this one‐night regatta, the self‐management of sleep/wake timing emerged as the most successful strategy. Among participants who adopted a shift‐based racing strategy, a short night shift duration (i.e., 2 h) significantly predicted a better placement. These findings confirmed the relevance of sleep management in sport performance and provided new insights into the most suitable sleep management strategy during a relatively short offshore regatta. The conclusions might apply also to similar continuous‐cycle activities. Further investigations are needed to explore best sleep management strategy in team regattas of longer duration.
Cadence‐based classification of moderate‐intensity overground walking in 41‐ to 85‐year‐old adults
Authors: Aguiar Elroy J. , Mora‐Gonzalez Jose , Ducharme Scott W. , Moore Christopher C. , Gould Zachary R. , Chase Colleen J. , Amalbert‐Birriel Marcos A. , Chipkin Stuart R. , Staudenmayer John , Zheng Peixuan , Tudor‐Locke Catrine 
Published: November 2022

BackgroundWalking cadence (steps/min) has emerged as a valid proxy of physical activity intensity, with consensus across numerous laboratory‐based treadmill studies that ≥100 steps/min approximates absolutely defined moderate intensity (≥3 metabolic equivalents; METs). We recently reported that this cadence threshold had a classification accuracy of 73.3% for identifying moderate intensity during preferred pace overground walking in young adults. The purpose of this study was to evaluate and compare the performance of a cadence threshold of ≥100 steps/min for correctly classifying moderate intensity during overground walking in middle‐ and older‐aged adults.MethodsParticipants (N = 174, 48.3% female, 41–85 years of age) completed laboratory‐based cross‐sectional study involving an indoor 5‐min overground walking trial at their preferred pace. Steps were manually counted and converted to cadence (total steps/5 min). Intensity was measured using indirect calorimetry and expressed as METs. Classification accuracy (sensitivity, specificity, accuracy) of a cadence threshold of ≥100 steps/min to identify individuals walking at ≥3 METs was calculated.ResultsThe ≥100 steps/min threshold demonstrated accuracy of 74.7% for classifying moderate intensity. When comparing middle‐ vs. older‐aged adults, similar accuracy (73.4% vs. 75.8%, respectively) and specificity (33.3% vs. 34.5%) were observed. Sensitivity was high, but was lower for middle‐ vs. older‐aged adults (85.2% vs. 93.9%, respectively).ConclusionA cadence threshold of ≥100 steps/min accurately identified moderate‐intensity overground walking. Furthermore, accuracy was similar when comparing middle‐ and older‐aged adults. These findings extend our previous analysis in younger adults and confirm the appropriateness of applying this cadence threshold across the adult lifespan.
Greenhouse gas emissions from decomposition of biosolids as affected by stabilization method and soil moisture
Authors: Obi‐Njoku Okenna , Boh Michael Yongha , Price Gordon W. , Gonzalez‐Pavia Andrea , Clark Osborne Grant 
Published: November 2022

AbstractComputational models are useful to estimate agricultural greenhouse gas emissions at regional scales. However, empirically based parameter values are required for the models to accurately represent carbon (C) and nitrogen (N) mineralization rates of different organic amendments in more and less humid regions or during wet and dry periods of the growing season. A controlled environment study was conducted to assess the rates of C and N mineralization in differently processed sewage sludge (biosolids) in wet and dry soil. Parameter values were estimated for use in modelling the degradation of three types of biosolids. A loam soil with either 49% water‐filled pore space (WFPS) or 29% WFPS was amended with mesophilic anaerobically digested (digested), alkaline‐stabilized, or composted biosolids. Headspace samples were collected and analysed for carbon dioxide (CO2) and nitrous oxide (N2O), and soil samples for nitrate () and ammonium (). Four different first‐order models were fitted to the cumulative CO2–C and N2O–N data (R2 > 0.98), and soil (R2 > 0.65) and (R2 > 0.93) concentrations. CO2–C data indicated that C mineralization was higher in soil with 49% WFPS than in soils with 29% WFPS. Seventy‐nine percent of the C compounds in digested biosolids degraded in soil with 49% WFPS, compared with 52% for alkaline‐stabilized biosolids and 8% for composted biosolids. The fitted coefficient values were similar for all of the four first‐order models used in this study and provide useful information for parameterizing more sophisticated mechanistic models of the degradation of biosolids in soil.
A contemporary reassessment of the enhanced transient expression system based on the tombusviral silencing suppressor protein P19
Authors: Jay Florence , Brioudes Florian , Voinnet Olivier 
Published: November 2022

SUMMARYTransient transgenic expression accelerates pharming and facilitates protein studies in plants. One embodiment of the approach involves leaf infiltration of Agrobacterium strains whose T‐DNA is engineered with the gene(s) of interest. However, gene expression during ‘agro‐infiltration’ is intrinsically and universally impeded by the onset of post‐transcriptional gene silencing (PTGS). Nearly 20 years ago, a simple method was developed, whereby co‐expression of the tombusvirus‐encoded P19 protein suppresses PTGS and thus enhances transient gene expression. Yet, how PTGS is activated and suppressed by P19 during the process has remained unclear to date. Here, we address these intertwined questions in a manner also rationalizing how vastly increased protein yields are achieved using a minimal viral replicon as a transient gene expression vector. We also explore, in side‐by‐side analyses, why some proteins do not accumulate to the expected high levels in the assay, despite vastly increased mRNA levels. We validate that enhanced co‐expression of multiple constructs is achieved within the same transformed cells, and illustrate how the P19 system allows rapid protein purification for optimized downstream in vitro applications. Finally, we assess the suitability of the P19 system for subcellular localization studies – an originally unanticipated, yet increasingly popular application – and uncover shortcomings of this specific implement. In revisiting the P19 system using contemporary knowledge, this study sheds light onto its hitherto poorly understood mechanisms while further illustrating its versatility but also some of its limits.
Effects of import taxes on intra‐African trade: New evidence from a case study of Malawi's imports
Authors: Chipeta Chinyamata , Montfaucon Angella Faith 
Published: November 2022

AbstractWe investigate the effect of import duty, import excise and import value‐added taxes (VAT) on Malawi's import prices, values and volumes in trading with Africa. We find that import taxes increase import prices, with import VAT having the largest impact. Import duties lead to higher import values, but by a much smaller extent and import duties and VAT have a positive relationship with import quantities from COMESA while a negative one with SADC countries. In relation to AfCFTA, an increase in relative market access increases the probability of a product being from an African country, while high import duties decrease the probability of Malawian importers trading with other African countries. The presence of import VAT further reduce these odds. Zero tariffs in the AfCFTA may only increase intra‐African trade marginally. Other policies on market access and other import taxes need to be assessed, while accounting for potential fiscal implications.
Cementing regional integration or building walls? Competition, cartels and regional integration in the cement industry in Africa
Authors: Roberts Simon , Simbanegavi Witness , Vilakazi Thando 
Published: November 2022

AbstractThe cement industry requires large‐scale energy and capital‐intensive plants, ideally located close to limestone deposits. These characteristics mean that there are substantial gains which can be realised from regional trade and competition in this inherently oligopolistic industry. This article analyses competition and trade in cement in Southern and East Africa. It considers how competition and coordination, new entry and competition enforcement have affected cross‐border trade and domestic prices in the countries of the East African Community and Southern African Development Community. We find that gains from trade through increased competition did not occur without there also being new entry to disrupt the incumbent firms which operated across the region. Entry at scale to supply regional markets led to substantial reductions in prices from the competition, in line with international studies of the effect of the cement cartels. The article points to the importance of prioritising competition enforcement as part of regional integration.
The trade effects of the African Continental Free Trade Area: An empirical analysis
Authors: Geda Alemayehu , Yimer Addis 
Published: November 2022

AbstractThis study examines the possible effects of the African Continental Free Trade Area (AfCFTA) agreement tariff reduction protocol on intra‐African goods trade using two approaches: trade indices and a gravity model. In both approaches, an attempt to identify the trade‐creation and trade‐diversion effects of the proposed AfCFTA is made. The two approaches combined suggest that the AfCFTA could raise intra‐African exports from the average annual value of US$ 72.7 billion (2015–2017) by about US$ 13.7 billion (by about 19%). For the success of the AfCFTA, the success in political activism needs to be combined with a continental industrial strategy that includes continental protection for infant industries in tandem with this continental liberalisation.