bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-vitamin K antagonist oral anticoagulants in older and frail patients with atrial fibrillation
Authors: Giugliano Robert P
Published: February 2022

Elderly and frail patients with atrial fibrillation (AF) are at increased risk of thrombotic events, bleeding, and death compared to their counterparts, making their management challenging. With the introduction of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in the past decade, the risk:benefit balance in such high-risk patients with AF has tipped in favor of treating these patients with anticoagulation, and in most cases with a NOAC instead of a VKA. In patients ≥75 years of age with AF, each of the 4 approved NOACs reduced stroke or systemic embolism and vs warfarin in their landmark clinical trial and lowered mortality. However, only apixaban and edoxaban significantly reduced major bleeding vs warfarin. A similar pattern was seen in even older cohorts (≥80 and ≥85 years). Among patients age ≥80 who are not candidates for oral anticoagulants at the approved dose, edoxaban 15 mg may be a reasonable alternative. In elderly or frail individuals who are on multiple comedications (particularly if ≥1 moderate or strong cytochrome P-450 inhibitor), only edoxaban consistently reduced major bleeding compared to warfarin. Regardless of the specific OAC selected, appropriate dosing in the elderly (who frequently qualify for dose reduction per the prescribing label) is critical. In elderly and frail patients with AF, factors that may modify the efficacy-safety profile of specific oral OACs should be carefully considered to permit the optimal selection and dosing in these vulnerable patients.
Optimizing adherence and persistence to non-vitamin K antagonist oral anticoagulant therapy in atrial fibrillation
Authors: Farinha José Maria , Jones Ian D , Lip Gregory Y H
Published: February 2022

Atrial fibrillation (AF) is associated with an increased risk of stroke, which can be prevented by the use of oral anticoagulation. Although non-vitamin K antagonist oral anticoagulants (NOACs) have become the first choice for stroke prevention in the majority of patients with non-valvular AF, adherence and persistence to these medications remain suboptimal, which may translate into poor health outcomes and increased healthcare costs. Factors influencing adherence and persistence have been suggested to be patient-related, physician-related, and healthcare system-related. In this review, we discuss factors influencing patient adherence and persistence to NOACs and possible problem solving strategies, especially involving an integrated care management, aiming for the improvement in patient outcomes and treatment satisfaction.
The Benefits of Friendliness: The Consequences of Positive Interpersonal Relations for Interstate Politics
Authors: Heimann Gadi , Kampf Zohar
Published: February 2022

While most international relations (IR) scholars tend to minimize the effect of relations between statespersons on foreign policy, this article argues that interpersonal relationships have more weight than the literature suggests. On the basis of twenty-one interviews conducted with senior Israeli statespersons, we propose a two-level model-linking positive interaction between statespersons and actual consequences at the state level. At the personal level, positive interactions can create receptiveness, build trust, facilitate accessibility and availability, and advance personal commitment. Translating these outcomes into consequences at the state level is mediated either by persuasion or by commitment. If persuasion is effective or there exists a high level of personal commitment, statespersons are more likely to succeed in mobilizing international support, removing obstacles to agreements, gathering sensitive information, and diffusing interstate tension. We conclude by discussing the limitations and advantages of good personal relations between statespersons and their implications for IR practice and theory.
EdgeCrafting: mining embedded, latent, nonlinear patterns to construct gene relationship networks
Authors: Husain Benafsh , Reed Bender Matthew , Alex Feltus Frank
Published: February 2022

The mechanisms that coordinate cellular gene expression are highly complex and intricately interconnected. Thus, it is necessary to move beyond a fully reductionist approach to understanding genetic information flow and begin focusing on the networked connections between genes that organize cellular function. Continued advancements in computational hardware, coupled with the development of gene correlation network algorithms, provide the capacity to study networked interactions between genes rather than their isolated functions. For example, gene coexpression networks are used to construct gene relationship networks using linear metrics such as Spearman or Pearson correlation. Recently, there have been tools designed to deepen these analyses by differentiating between intrinsic vs extrinsic noise within gene expression values, identifying different modules based on tissue phenotype, and capturing potential nonlinear relationships. In this report, we introduce an algorithm with a novel application of image-based segmentation modalities utilizing blob detection techniques applied for detecting bigenic edges in a gene expression matrix. We applied this algorithm called EdgeCrafting to a bulk RNA-sequencing gene expression matrix comprised of a healthy kidney and cancerous kidney data. We then compared EdgeCrafting against 4 other RNA expression analysis techniques: Weighted Gene Correlation Network Analysis, Knowledge Independent Network Construction, NetExtractor, and Differential gene expression analysis.
Participatory research in health promotion: a critical review and illustration of rationales
Authors: Harting Janneke , Kruithof Kasper , Ruijter Lotte , Stronks Karien
Published: February 2022

In health promotion research, enthusiasm for patient and public involvement (PPI) is growing. However, a lack of conceptual clarity leads to ambiguities in participatory processes and purposes, and hampers efforts to achieve and evaluate PPI in research. This study provides an overview of its underlying reasons—or rationales—so as to better understand, guide and interpret PPI in research practice. We conducted a critical review to identify typologies of rationales for PPI. We re-categorized the different types of rationales from these typologies based on their content. We illustrated the resulting categories of rationales with examples from a case study on PPI in research on Lyme disease. Five categories of rationales for PPI were identified. The democratic rationale reflects the normative right of citizens to have a voice in research. The consumerist rationale refers to the economic right of stakeholders with interests to have a say. Rooted in social justice, the transformative rationale seeks to empower marginalized groups. The substantive rationale starts from epistemic considerations and aims to improve the quality of knowledge that research generates. The instrumental rationale is of pragmatic origin and refers to improved efficiency and effectiveness of the research. Our overview of categories of rationales can be used as a frame of reference for PPI in health promotion research. Exploring, stating explicitly and reflecting on the underlying reasons for PPI may help to define realistic purposes, select matching approaches and design appropriate evaluation studies. This might also contribute to the conceptualization of PPI.
Modeling carbon dioxide emission of countries in southeast of Asia by applying artificial neural network
Authors: Komeili Birjandi Ali , Fahim Alavi Morteza , Salem Mohamed , Assad Mamdouh El Haj , Prabaharan Natarajan
Published: February 2022

Energy and economy play a substantial role in environmental issues such as the emission of greenhouse gases. CO2 is one of the greenhouses that is hugely produced in industrial processes and other human being activities. The major share of CO2 emission is related to the energy-related activities. As a result, modeling the amount of produced CO2 by utilization of different energy sources must be considered. Moreover, by considering economic indicators such as gross domestic product, the accuracy of the model could be improved. In the present work, artificial neural network (ANN) with two transfer functions including normalized radial basis and tansig is used to model CO2 production of different countries in Southeast Asia including Malaysia, Indonesia, Singapore and Vietnam. It is observed that using the network with normalized radial basis and 11 neurons in the hidden layer provides the model with the highest precision with an R2 of 0.9997 while the optimal architecture of the network using tansig function provides a model with R2 of 0.9996.
Is It Friendship? An Analysis of Contemporary German–Israeli Relations
Authors: Berenskötter Felix , Mitrani Mor
Published: February 2022

This article explores the nature of the contemporary “special relationship” between Germany and Israel. Having emerged out of the ashes of the Second World War and the Holocaust, political relations between these two states are widely seen as having successfully undergone a process of reconciliation. A key feature is German support for Israel, usually understood as a constant attempt to pay off a historical debt in exchange for rehabilitation and recognition of Germany as a “good state.” The article probes another interpretation by asking whether contemporary German–Israeli relations have reached the stage of friendship, a relationship structured by care rather than guilt. To this end, it presents an original conceptual framework of interstate friendship as a bond of shared memories and visions that enable a common orientation toward the past and the future both sides are committed to invest in. Applied to an interpretive analysis of the “sharedness” of the memory of the Holocaust and the vision of a secure Israel, the paper finds strong evidence for the former yet significant gaps in the latter, concluding that relations between the states of Germany and Israel still fall short of friendship.
Accessibility, Optimism and Technology
Authors: Cooper Martin
Published: February 2022

Technology, when made well, can give people with disabilities choice and empower them to achieve their goals. Robin Christopherson MBE tells Martin Cooper MBCS why he loves smartphones and wants a driverless car.
Inclusion: The Final Frontier
Authors: Perera Mickela
Published: February 2022

Mickela Perera has been improving accessibility across the UK’s biggest brands for over a decade. She tells Johanna Hamilton AMBCS why good UX is key to unlocking truly inclusive design.
Inclusive Data Processing of Sex, Gender and Titles
Authors: Holt Danny
Published: February 2022

Danny Holt CITP MBCS talks about their experiences of using IT as a non-binary person.
Leadership
Authors: Hall Jon G
Published: February 2022

Jon G Hall CITP FBCS explores the all-too familiar struggle behind getting to ‘Yes!’
Understanding Online Harms and How to Fix the Problem
Authors: Simmons Abigail , Short Emma , Phippen Andy
Published: February 2022

From cyberbullying to stalking and transphobia, online harms are damaging lives. Abigail Simmons of Trans Tent, Dr Emma Short of De Montford University and Professor Andy Phippen of Plymouth University dissect the problem and explore possible solutions.
Cybersecurity
Authors: Ratnayake Deepthi
Published: February 2022

Dr Deepthi Ratnayake explores the impact of dark patterns on web applications.
HIV-1 drug resistance mutations among individuals with low-level viraemia while taking combination ART in Botswana
Authors: Bareng Ontlametse T , Moyo Sikhulile , Zahralban-Steele Melissa , Maruapula Dorcas , Ditlhako Tsotlhe , Mokaleng Baitshepi , Mokgethi Patrick , Choga Wonderful T , Moraka Natasha O , Pretorius-Holme Molly , Mine Madisa O , Raizes Elliot , Molebatsi Kesaobaka , Motswaledi Modisa S , Gobe Irene , Mohammed Terence , Gaolathe Tendani , Shapiro Roger , Mmalane Mompati , Makhema Joseph M , Lockman Shahin , Essex Max , Novitsky Vlad , Gaseitsiwe Simani ,   the PANGEA consortium, Ayles Helen , Abeler-Dörner Lucie , Bonsall David , Bowden Rory , Essex Max , Fidler Sarah , Fraser Christophe , Grabowski Kate , Golubchik Tanya , Gupta Ravindra , Hayes Richard , Herbeck Joshua , Kagaayi Joseph , Kaleebu Pontiano , Lingappa Jairam , Novitsky Vladimir , Moyo Sikhulile , Pillay Deenan , Quinn Thomas , Rambaut Andrew , Ratmann Oliver , Seeley Janet , Ssemwanga Deogratius , Tanser Frank , Wawer Maria
Published: February 2022

Objectives

To assess whether a single instance of low-level viraemia (LLV) is associated with the presence of drug resistance mutations (DRMs) and predicts subsequent virological failure (VF) in adults receiving ART in 30 communities participating in the Botswana Combination Prevention Project.

Methods

A total of 6078 HIV-1 C pol sequences were generated and analysed using the Stanford HIV drug resistance database. LLV was defined as plasma VL = 51–999 copies/mL and VF was defined as plasma VL ≥ 1000 copies/mL.

Results

Among 6078 people with HIV (PWH), 4443 (73%) were on ART for at least 6 months. Of the 332 persons on ART with VL > 50 copies/mL, 175 (4%) had VL ≥ 1000 copies/mL and 157 (4%) had LLV at baseline. The prevalence of any DRM was 57 (36%) and 78 (45%) in persons with LLV and VL ≥ 1000 copies/mL, respectively. Major DRMs were found in 31 (20%) with LLV and 53 (30%) with VL ≥ 1000 copies/mL (P = 0.04). Among the 135 PWH with at least one DRM, 17% had NRTI-, 35% NNRTI-, 6% PI- and 3% INSTI-associated mutations. Among the 3596 participants who were followed up, 1709 (48%) were on ART for ≥6 months at entry and had at least one subsequent VL measurement (median 29 months), 43 (3%) of whom had LLV. The OR of experiencing VF in persons with LLV at entry was 36-fold higher than in the virally suppressed group.

Conclusions

A single LLV measurement while on ART strongly predicted the risk of future VF, suggesting the use of VL > 50 copies/mL as an indication for more intensive adherence support with more frequent VL monitoring.
Modeling and Forecasting Volatilities of Financial Assets with an Asymmetric Zero-Drift GARCH Model
Authors: Shi Yanlin
Published: February 2022

In this study, we extend the zero-drift generalized autoregressive conditional heteroskedasticity (GARCH) model to incorporate the well-known asymmetric effects of shocks on financial volatility and propose an asymmetric zero-drift GARCH (AZD-GARCH) model. Relevant asymptotics of the new model, including those for the quasi-maximum-likelihood estimator and the powers of the stability test and the model misspecification test, are comprehensively discussed with simulation evidence. Our empirical studies focus on the daily Brent oil price, the AUD/USD exchange rate, and the S&P 500 returns covering the recent 2019–2020 period. The results demonstrate the usefulness of the AZD-GARCH model in understanding the volatility features of financial assets and the model’s superiority to a range of competitors in precisely forecasting volatilities. Robustness checks on data for extended sample periods (2017–2020 and 2009–2020) further provide highly consistent results. Therefore, the proposed AZD-GARCH model can help policymakers and market participants in various applications, such as monitoring asset volatility and hedging relevant risks.
Carmo and Jones’ logic for contrary-to-duty obligations revised
Authors: Carmo José , Jones Andrew J I
Published: February 2022

We revise our logic for contrary-to-duty (CTD) conditionals, showing how to adjust our logical models in such a way as to avoid the counterintuitive results pointed out by Bjørn Kjos-Hanssen, but keep the main results that support our logical analysis of CTD scenarios.
Vetting asteroseismic Δν measurements using neural networks
Authors: Reyes Claudia , Stello Dennis , Hon Marc , Zinn Joel C
Published: February 2022

Precise asteroseismic parameters can be used to quickly estimate radius and mass distributions for large samples of stars. A number of automated methods are available to calculate the frequency of maximum acoustic power (νmax) and the frequency separation between overtone modes (Δν) from the power spectra of red giants. However, filtering through the results requires manual vetting, elaborate averaging across multiple methods or sharp cuts in certain parameters to ensure robust samples of stars free of outliers. Given the importance of ensemble studies for Galactic archaeology and the surge in data availability, faster methods for obtaining reliable asteroseismic parameters are desirable. We present a neural network classifier that vets Δν by combining multiple features from the visual Δν vetting process. Our classifier is able to analyse large numbers of stars, determining whether their measured Δν are reliable and thus delivering clean samples of oscillating stars with minimal effort. Our classifier is independent of the method used to obtain νmax and Δν, and therefore can be applied as a final step to any such method. Tests of our classifier’s performance on manually vetted Δν measurements reach an accuracy of 95 per cent. We apply the method to giants observed by the K2 Galactic Archaeology Program and find that our results retain stars with astrophysical oscillation parameters consistent with the parameter distributions already defined by well-characterized Kepler red giants.
Evidence in favour of density wave theory through age gradients observed in star formation history maps and spatially resolved stellar clusters
Authors: Abdeen Shameer , Davis Benjamin L , Eufrasio Rafael , Kennefick Daniel , Kennefick Julia , Miller Ryan , Shields Deanna , Monson Erik B , Bassett Calla , O’Mara Harry
Published: February 2022

Quasi-stationary density wave theory predicts the existence of an age gradient across the spiral arms with a phase crossing at the corotation radius. We have examined evidence for such age gradients using star formation history (SFH) maps derived from lightning, a spectral energy distribution fitting procedure, and by using spatially resolved stellar clusters. Three galaxies from the LEGUS survey were used to analyse the azimuthal offsets of spatially resolved stellar clusters. Kernel density estimation plots of azimuthal cluster distance offsets reveal prominent central peaks and secondary peaks on the positive side, relative to the density wave for NGC 5194 and NGC 5236. These secondary downstream peaks in the cluster distributions show overall evidence for an age gradient. NGC 628 shows secondary peaks on both sides of the density wave. The cluster distributions also show an increasing spatial spread with age, consistent with the expectation that they were born in the density wave. SFH maps of 12 nearby galaxies were analysed using spirality, a matlab-based code, which plots synthetic spiral arms over FITS images. The SFH maps reveal a gradual decrement (tightening) in pitch angles with increasing age. By analysing the pitch angle differences between adjacent age bins using the error function, the average of the probabilities shows a $69{{\ \rm per\ cent}}\pm 25{{\ \rm per\ cent}}$ chance that the pitch angle values decrease (tighten) with increasing age. Thus, we see a tightening of the spiral pattern in galaxies, both when segregating stellar populations specifically by age or more generally by colour, as was shown in our previous studies.
The puzzling story of flare inactive ultra fast rotating M dwarfs – I. Exploring their magnetic fields
Authors: Doyle Lauren , Bagnulo Stefano , Ramsay Gavin , Doyle J Gerry , Hakala Pasi
Published: February 2022

Stars which are rapidly rotating are expected to show high levels of activity according to the activity–rotation relation. However, previous TESS studies have found ultra fast rotating (UFR) M dwarfs with periods less than 1 d displaying low levels of flaring activity. As a result, in this study, we utilize VLT/FORS2 spectro-polarimetric data of 10 M dwarf UFR stars between spectral types ∼M2–M6 all with Prot < 1, to detect the presence of a magnetic field. We divide our sample into rotation period bins of equal size, with one star having many more flares in the TESS light curve than the other. We also provide an analysis of the long-term variability within our sample using TESS light curves taken during Cycles 1 and 3 (up to 3 yr apart). We identify 605 flares from our sample which have energies between 2.0 × 1031 and 5.4 × 1034 erg. Although we find no significant difference in the flare rate between the Cycles, two of our targets display changes in their light-curve morphology, potentially caused by a difference in the spot distribution. Overall, we find five stars (50 per cent) in our sample have a detectable magnetic field with strengths ∼1–2 kG. Of these five, four were the more flare active stars within the period bins with one being the less flare active star. It would appear the magnetic field strength may not be the answer to the lack of flaring activity and supersaturation or magnetic field configuration may play a role. However, it is clear the relationship between rotation and activity is more complex than a steady decrease over time.
Genetic monitoring of the Critically Endangered Araripe Manakin reveals low diversity and declining effective population size
Authors: Luna Leilton Willians , Marques Silva Sofia , Andrade de Girão e Silva Weber , Garbim Gaiotti Milene , Macedo Regina H , Araripe Juliana , Sena do Rêgo Péricles
Published: February 2022

Genetic information is still underestimated in conservation policies, seldom being monitored or included in management strategies. Monitoring changes in genetic diversity over time in endangered species is useful to anticipate possible risks associated with reduced genetic variation. The Araripe Manakin (Antilophia bokermanni) is a Critically Endangered species, probably with a historically low level of genetic diversity and currently facing demographic population decline. This is the first study to present a fine-scale spatio-temporal genetic monitoring for the Araripe Manakin. Using microsatellite loci, genotyped at two time periods (2003–2004 and 2015–2017), we conclude that genetic diversity has been relatively stable in this short-term assessment, with limited signs of population structure between time frames, and no current population structure within past or present species distribution. However, we also detect signs of genetic bottleneck and evidence that suggest that mating is not presently random. Our results corroborate that the species is a resilient bird, but habitat loss and degradation are jeopardizing Araripe Manakin’s persistence. The species comprises a unique small population, and restoration of habitat quality and connectivity should continue to maintain its viability. Nonetheless, given the low genetic diversity observed, we further identify some challenges and recommend solutions for the implementation of genetic information in the current conservation effort of the Araripe Manakin.
Multiple sgRNAs for one-step inactivation of the duplicatedacetyl-coenzyme A carboxylase 2(ACC2) genes inBrassica napus
Authors: LaManna Lisa M , Parulekar Mugdha S , Maliga Pal
Published: February 2022

Efficient plastid transformation in Arabidopsis (Arabidopsis thaliana) requires genetic lines that are hypersensitive to spectinomycin due to the absence of a chloroplast acetyl-coenzyme A carboxylase (ACCase) encoded in the acetyl-coenzyme A carboxylase 2 (ACC2) nuclear gene. To obtain plastid transformation-competent oilseed rape (Brassica napus), we inactivated all nuclear encoded, chloroplast targeted ACCase copies using CRISPR–Cas9. Brassica napus (2n = 38, AACC) is a recent interspecific hybrid of Brassica rapa (2n = 20, AA) and B. oleracea (2n = 18, CC) and is expected to have at least two ACC2 copies, one from each parent. The sequenced genome has two ACC2 copies, one that is B. rapa-like and one that is B. oleracea-like. We designed single-guide RNAs (sgRNAs) that could simultaneously inactivate both nuclear ACC2 copies. We expressed Cas9 from a chimeric egg cell promoter 1.2 (EC1.2p) known to yield homozygous or biallelic mutants in Arabidopsis in the T1 generation. To maximize the probability of functionally inactivating both orthologs in a single step, each of the two vectors carried four sgRNAs. Four T0 transgenic lines were obtained by Agrobacterium tumefaciens-mediated hypocotyl transformation. Amplicon sequencing confirmed mutations in ACC2 genes in 10 T1 progeny, in seven of which no wild-type (WT) copy remained. The B. napus T2 seedlings lacking WT ACC2 gene copies exhibited a spectinomycin hypersensitive phenotype, suggesting that they will be a useful resource for chloroplast genome transformation.
Ixekizumab in radiographic axial spondyloarthritis with and without elevated C-reactive protein or positive magnetic resonance imaging
Authors: Maksymowych Walter P , Bolce Rebecca , Gallo Gaia , Seem Emily , Geneus Vladimir J , Sandoval David M , Østergaard Mikkel , Tada Kurisu , Baraliakos Xenofon , Deodhar Atul , Gensler Lianne S
Published: February 2022

Objective

To evaluate response rates at week 16 with ixekizumab in patients with radiographic axial SpA (r-axSpA) and elevated or normal/low baseline inflammation measured by serum CRP or spinal MRI using data from two randomized, double-blind, placebo (PBO)-controlled phase III trials.

Methods

Biologic-naïve (COAST-V) or TNF inhibitor-experienced (COAST-W) adults with active r-axSpA received 80 mg ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W) or PBO or active reference [40 mg adalimumab every 2 weeks (ADAQ2W) in COAST-V. At week 16, patients receiving ixekizumab continued as assigned and patients receiving PBO or ADA were rerandomized 1:1 to IXEQ2W or IXEQ4W through week 52. Assessment of SpondyloArthritis international Society 40% (ASAS40) response rates were examined by baseline CRP (≤5 or >5 mg/l) and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine inflammation score (<2 or ≥2).

Results

In the COAST-V/W integrated dataset (N = 567), significantly more patients treated with ixekizumab achieved ASAS40 response at week 16 by CRP ≤5 mg/l (27% IXEQ4W, P < 0.05; 35% IXEQ2W, P < 0.01 vs 12% PBO), CRP >5 mg/l (39% IXEQ4W, P < 0.001; 43% IXEQ2W, P < 0.001 vs 17% PBO), SPARCC MRI spine score <2 (40% IXEQ4W P < 0.01, 52% IXEQ2W P < 0.001 vs 16% PBO), and SPARCC MRI spine score ≥2 (44% IXEQ4W P < 0.001, 47% IXEQ2W P < 0.001 vs 19% PBO). ASAS40 response was observed with CRP ≤5 mg/l and SPARCC MRI spine score <2 with IXEQ4W (29%) and was significant with IXEQ2W (48%; P < 0.05) vs PBO (13%).

Conclusion

Ixekizumab demonstrated efficacy in the treatment of AS/r-axSpA in patients with and without elevated CRP or evidence of spinal inflammation on MRI.

Trial registration

ClinicalTrials.gov (https://clinicaltrials.gov): NCT02696785, NCT02696798
AaTAS1 and AaMFS1 Genes for Biosynthesis or Efflux Transport of Tenuazonic Acid and Pathogenicity of Alternaria alternata
Authors: Sun Fan , Cao Xueqiang , Yu Dianzhen , Hu Dongqiang , Yan Zheng , Fan Yingying , Wang Cheng , Wu Aibo
Published: February 2022

Taking tenuazonic acid (TeA) synthetase 1 (TAS1) in Pyricularia oryzae as a reference, the homolog AaTAS1 was first anchored in Alternaria alternata via de novo sequencing. Subsequently, AaMFS1, as a major facilitator superfamily (MFS) protein–encoding gene in the adjacent upstream region, was followed with interest. As hypothesized, AaTAS1 is required for TeA biosynthesis, while AaMFS1 is an efflux pump for the transmembrane transport of TeA. Comparatively, the TeA yield of ΔAaTAS1 and ΔAaMFS1 dropped significantly compared with that of the wild-type strain. Specifically, the A domain of AaTAS1 catalyzed the start of TeA biosynthesis in vitro. Simultaneously, the pathogenicity of ΔAaTAS1 was also significantly decreased. Transcriptome analysis confirmed the abovementioned consistency between the TeA-producing phenotypes and related gene expression. Moreover, the proteins AaTAS1 and AaMFS1 were found present in the cytoplasm, plasma membrane, and intracellular membrane system, respectively, by fluorescence localization. Namely, AaTAS1 was responsible for the biosynthesis of TeA, and AaMFS1 was responsible for the efflux transport of TeA. Certainly, AaTAS1 indirectly regulated the expression of AaMFS1 through the level of synthetic TeA. Overall, data on the novel AaTAS1 and AaMFS1 genes mainly contribute to theoretical advances in mycotoxin biosynthesis and the pathogenicity of phytopathogens to agricultural foods.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Dealing with the Displaced Nipple–Areola Complex in Macromastia Using a Superomedial Pedicle and Inverted T Pattern
Authors: Hudson Donald A. , Lelala N. Bruce
Published: February 2022

Background:

In macromastia, especially in patients with a raised BMI, the nipple areola complex (NAC) may be displaced from the breast midline/meridian. This is poorly documented, and there is little published on surgical management. The aim of the study was to identify the incidence of displaced NAC in macromastia and discuss the management using the superomedial pedicle, by canting the vertical limbs of the inverted T/keyhole. The study also aimed to postulate a theory of pathogenesis.

Methods:

The study is a retrospective review for a two-and-a-half year period. For study inclusion, the NAC had to be displaced 3 cm or more from the breast meridian. A superomedial pedicle was used with an inverted T pattern. The vertical limbs of the keyhole were canted medially for medially displaced NACs and laterally for laterally displaced NACs.

Results:

Fifteen patients were identified: three with medial and 12 with laterally displaced NAC. Mean age was 35 years (range 21–61) with a mean BMI of 31 (range 27–37). The mean mass of tissue excised was 1158 g (range 330–1969 g). The mean follow up is 7 months (range 2–21 months). One patient suffered partial areola loss, and 2 patients had a breakdown at the angle of sorrow/inverted T junction.

Conclusions:

The displaced NAC is not uncommon in women with a raised BMI presenting for breast reduction. Canting the vertical limbs of the keyhole away from the deviated NAC yields satisfactory results in treating patients with a displaced NAC using a superomedial pedicle. A theory of possible pathogenesis is postulated; global attenuation of the breast footplate occurs, leading to lateral and inferior displacement of the NAC.
Median Nerve Traction Caused by Palmaris Profundus Muscle: A Case Report
Authors: Flores Tonatiuh , Sabitzer Hugo , Bergmeister Konstantin D. , Schatten Philipp , Pollhammer Michael , Metzger Gerald , Schrögendorfer Klaus F.
Published: February 2022

The palmaris longus muscle is one of the most variant muscles in the human body. Its variations such as the palmaris profundus can cause nerve compression symptoms. Here, we present a case of severe nerve affection due to a palmaris profundus muscle. The palmaris profundus tendon was partially resected at intervention. Pain symptoms started immediately after wearing off of the local anesthetic, and revision surgery had to be performed. Severe traction on the median nerve by the palmaris profundus tendon could be observed at revision. The resection of the palmaris profundus tendon instantly eased the patient’s severe pain. At preoperative examination and planning of surgery, the palmaris profundus was not detected. As there is no test for the detection of anatomic variations of the palmaris longus muscle at physical examination, discovering such anomalies is not possible without imaging tools. Ultrasonographic examinations aid in preoperative planning of carpal tunnel release, especially at revision surgeries.
Supercharging the Smile: A Novel Dual Nerve Transfer for Facial Reanimation
Authors: Kuta Victoria , Taylor S. Mark
Published: February 2022

Background:

Facial paralysis has profound effects on the functional and psychosocial well-being of patients. Various surgical facial reanimation techniques have been described to address this devastating condition. While traditional surgical approaches have proved successful in restoring either facial tone or facial movement, newer combination nerve transfer techniques are addressing the limitations of the traditional single nerve transfer approaches.

Methods:

This study aimed to describe a promising new surgical approach to facial reanimation utilizing a dual nerve transfer to maximize both resting and active symmetry while minimizing postoperative synkinesis. Here, we use the masseteric nerve to selectively innervate the midface in combination with a hypoglossal facial nerve graft to reanimate the remaining facial regions.

Results:

To date, we have performed this operation on four patients, all of whom tolerated the procedure well. Our patients are showing significant improvements in both resting facial tone and facial movement with no signs of synkinesis at 9 months postoperative.

Conclusions:

We believe this dual nerve transfer to be superior in restoring the combination of tone, symmetry, and movement to the paralyzed face when compared with traditional single nerve transfer approaches.
Unilateral Cleft Lip Repair: Technical Maneuvers to Achieve Vermilion and Mucosal Height
Authors: Chiang Sarah N. , Zubovic Ema , Skolnick Gary B. , Patel Kamlesh B.
Published: February 2022

Background:

Patients with unilateral cleft lip often require secondary procedures due to asymmetric fullness or deficiencies along the mucosal free margin of the upper lip. Here, we describe our technique for mucosal advancement and repair to attain symmetry.

Methods:

Maneuvers to obtain vermilion and mucosal height include (1) use of a tailored vermilion flap; (2) supraperiosteal release of the lesser segment; (3) backcut “poker incision” to mobilize the mucosal flap on the lesser segment; (4) transverse release of mucosa across the greater segment; (5) accurate reduction along vermilion-mucosal junction; and (6) bilateral medial mucosal advancement. To examine postoperative outcomes, photographic data were available for 14 patients with unilateral complete cleft lip. The Cleft Lip Component Symmetry Index was then calculated as a ratio of upper lip height on cleft to noncleft sides, where an index of 1 indicates symmetry.

Results:

Sixteen consecutive patients underwent unilateral cleft lip repair with this technique over a 3-year period, none of whom have required secondary operations. The symmetry index for 14 of 16 patients was 1.02 ± 0.11 (95% confidence interval [0.96, 1.08], P = 0.56), demonstrating satisfactory upper lip symmetry.

Conclusions:

Postoperative asymmetry after unilateral cleft lip repair, particularly along the free margin, continues to be a common problem, necessitating secondary procedures. The technique of mucosal repair merits more careful attention than it has previously received, and here we describe in detail a method that has allowed for improved symmetry.
Ventricular Infusion and Nanoprobes Identify Cerebrospinal Fluid and Glymphatic Circulation in Human Nerves
Authors: Pessa Joel E.
Published: February 2022

Background:

Growing evidence suggests that cerebrospinal fluid circulates in human nerves. Several conditions encountered by the plastic surgeon may be related to dysregulation of this system, including nerve transection, stretch injuries, and peripheral neuropathy. The purpose of this study was to show how ventricular infusion and nanoprobes identify CSF and glymphatic circulation in neural sheaths of human nerves.

Methods:

The technique of ventricular infusion using buffered saline was developed in 2017. The technique was used in a series of eight fresh cadavers before dissection of the median nerve, and combined with fluorescent imaging and nanoprobe injections in selected specimens.

Results:

Eight cadaver specimens underwent ventricular infusion. There were six female and two male specimens, ages 46–97 (mean 76.6). Ventricular cannulation was performed successfully using coordinates 2 cm anterior to coronal suture and 2.5 cm lateral to sagittal suture. Depth of cannulation ranged from 44 to 56 mm (mean 49.7). Ventricular saline infusion complemented by nanoprobe injection suggests CSF flows in neural sheaths, including pia meninges, epineurial channels, perineurium, and myelin sheaths (neurolemma).

Conclusions:

Ventricular infusion and nanoprobes identify CSF flow in neural sheaths of human nerves. CSF flow in nerves is an open circulatory system that occurs via channels, intracellular flow, and cell-to-cell transport associated with glial cells. Neural sheaths, including neurolemma, may participate in glucose and solute transport to axons. These techniques may be used in anatomic dissection and live animal models, and have been extended to the central nervous system to identify direct ventricle-to-pia meninges CSF pathways.
Management of Acute Complicated Mastoiditis
Authors: Kaufmann Matthew R. , Shetty Kunal , Camilon P. Ryan , Shetty Anisha , Levi Jessica R. , Devaiah Anand K.
Published: February 2022

Background:

The objective of our study was to evaluate the efficacy of treatment options for the most frequently reported complications of acute mastoiditis in the English literature. PubMed, EMBASE, and The Cochrane Library were searched from database inception through March 29, 2019.

Methods:

Two independent reviewers (M.R.K., K.S.) evaluated search results for study inclusion. References cited in publications meeting inclusion criteria were reviewed. Twenty-three included studies were published from 1998 through 2018. Treatment efficacy was determined by comparing the change in number of complication subtypes in each treatment subgroup (medical, conservative, or surgical) from admission to discharge (range: 5–30 days) or postdischarge follow-up (range: 1–27.5 months) with a random effects model.

Results:

Among 733 identified articles, 23 met inclusion criteria. Of the 883 included patients, 203 were managed medically (23%), 300 conservatively (34%) and 380 surgically (43%). Conservative patients had more extracranial complications (ECC, P = 0.04) and intratemporal complications (IT, P = 0.04) at follow-up compared with medical patients. Medical patients had more total number of complications (TNC, P = 0.03), ECC (P = 0.02), and IT (P = 0.01) at discharge compared with surgical patients. Conservative patients had more of all complications except intracranial/extracranial abscess and “other” at discharge and follow-up compared with surgical patients.

Conclusions:

There were larger reductions in TNC, ECC, and IT at discharge and follow-up among surgical patients compared with medical and conservative patients. There were greater reductions in TNC, ECC, IT, intracranial complications, subperiosteal abscess and lateral sinus thrombosis at discharge and follow-up among surgical patients compared with conservative patients.
Very Low Incidence of SARS-CoV-2, Influenza and RSV but High Incidence of Rhino-, Adeno- and Endemic Coronaviruses in Children With Acute Respiratory Infection in Primary Care Pediatric Practices During the Second and Third Wave of the SARS-CoV-2 Pandemic
Authors: Engels Geraldine , Sack Johanna , Weissbrich Benedikt , Hartmann Katrin , Knies Kerstin , Härtel Christoph , Streng Andrea , Dölken Lars , Liese Johannes G. ,   for the CoPraKid Study Group
Published: February 2022

Respiratory viruses were detected by multiplex-polymerase chain reaction from oropharyngeal swabs in 114/168 (67.9%) children with acute respiratory infection presenting to 5 pediatric practices in Germany between November 2020 and April 2021. In contrast to rhino- (48.8%), adeno- (14.3%) and endemic coronaviruses (14.9%), SARS-CoV-2 and influenza virus were detected only once; respiratory syncytial virus was not detected. This demonstrates differing impacts of pandemic infection control measures on the spread of respiratory viruses.
Spyramicine and Trimethoprim-Sulfamethoxazole Combination to Prevent Mother-To-Fetus Transmission of Toxoplasma gondii Infection in Pregnant Women: A 28-Years Single-center Experience
Authors: Buonsenso Danilo , Pata Davide , Turriziani Colonna Arianna , Iademarco Mariella , De Santis Marco , Masini Lucia , Conti Guido , Molle Fernando , Baldascino Antonio , Acampora Anna , Luciano Rita , Gallini Francesca , Valentini Piero
Published: February 2022

Background:

There is weak evidence on the best treatment of pregnant women with Toxoplasma gondii infection to prevent the vertical transmission to the fetus.

Methods:

We conducted a 28-year retrospective study aiming to compare the efficacy of three therapeutic regimens [Spiramicyn alone (Spy) vs. Pyrimethamine-Sulfadiazine (P/S) vs. Spiramicyn with Trimethoprim-Sulfamethoxazole (Spy+TMP-SMX)] for the prevention of mother-to-fetus transmission of T. gondii infection.

Results:

170 women were included: 58 (34.1%) had certain congenital toxoplasmosis (CT), 61 (35.9%) a probable infection and 41 (24.1%) possible infection. In total 97 mothers (57.1%) were treated with the Spy+TMP-SMX combination, 64 mothers (37.6%) were treated with Spy only and 8 mothers (4.7%) with P/S. Infected infants were 20/170 (11.7%). However, 8.2% (8/97) of infants born to mothers treated with Spy+TMP-SMX were infected, 20% (11/55) of infants born to women treated with Spy and 12.5% (1/8) of infants born to mothers treated with P/S were infected. Logistic regression analysis demonstrated that Spy treatment alone was associated with an increased risk of CT compared to the Spy+TMP-SMX combination (OR, 2.78, 95% CI 1.04-7.41, P value 0.041). No difference was observed when the Spy+TMP-SMX was compared with the P/S combination (OR 1.59; 95% CI 0.17 - 14.58; P value 0.682). Results were confirmed when the analyses were corrected by trimester of infection and by type of maternal treatment (OR 7.72; 95% CI 3.40-17.53, P value <0.001).

Conclusions:

The combination of Spy+TMP-SMX may be more effective in reducing the risk of maternal-fetal transmission of Toxoplasmosis compared to Spy alone; furthermore, this combination is not inferior to P/S, the current international standard-of-care maternal treatment for the prevention of CT. A prospective trial comparing the combination Spy+TMP-SMX with P/S would be necessary to provide definitive evidence on the best regimen for pregnant women with T. gondii infection.
The Effects of Experiential Learning on Perceived Clinical Reasoning and Self-efficacy of Doctor of Physical Therapy Students
Authors: Lowe Leah , Flowers Meredith , Fletcher James , Yates Charlotte
Published: February 2022

Introduction and Review of the Literature.

Experiential learning (EL) is an instructional method that is increasingly being used to teach Doctor of Physical Therapy (DPT) pediatric content. However, there remains a paucity of research describing student outcomes resulting from EL courses compared with outcomes resulting from traditional instruction-based courses. The purpose of this study was to evaluate the change in perceived clinical reasoning and self-efficacy experienced by DPT students from the same DPT program who completed either high (at least 15 hours) or low (3 hours or less) pediatric EL as a component of their required, semester-long pediatric course.

Subjects and Methods.

The study was a pretest–posttest comparison group design. Second-year DPT students (n = 58; male: 19 and female: 39) enrolled in fall 2018 (high EL group) and students (n = 53; male: 18 and female: 35) enrolled in fall 2020 (low EL group) completed the Self-Assessment of Clinical Reflection and Reasoning (SACRR) and the Physical Therapy Self-Efficacy Scale (PTSE) during the first and last week of the pediatrics course.

Results.

A significant interaction effect between EL dosage and time was found for the SACRR (F
1,106 = 51.03, P = .000, partial eta squared = 0.33), suggesting that the change in scores was influenced by the dosage of EL. There was no significant interaction effect between EL dosage and time for the PTSE (F
1,104 = 1.13, P = .29, partial eta squared = .01). There was a significant main effect for time (F
1,104 = 225.61, P = .000, partial eta squared = .68), with both groups showing an improvement in pediatric physical therapy self-efficacy.

Discussion and Conclusion.

The results of this study suggest that the perceived self-efficacy abilities of students improved with all instructions, but the addition of high EL may enhance traditional instruction methods when used to aid DPT students in the development of self-perceived clinical reasoning and reflection skills.
Beyond the Musculoskeletal System: Considering Whole-Systems Readiness for Running Postpartum
Authors: Donnelly Gráinne M. , Brockwell Emma , Rankin Alan , Moore Isabel S.
Published: February 2022

Background:

Postpartum women frequently engage in running. In the absence of official guidance on returning-to-running postpartum, physical therapists rely on clinical experience alongside the available literature. Subsequently, the traditional evaluation of postpartum readiness for running tends to focus on musculoskeletal factors. This clinical commentary addresses how to evaluate and manage postpartum return-to-running in a systematic order by discussing relevant whole-systems considerations beyond the musculoskeletal system, while also highlighting possible interactions between relevant considerations.

Discussion:

Using a whole-systems biopsychosocial approach, physical therapists should consider the following when managing and evaluating readiness to return-to-running: physical deconditioning, changes to body mass, sleeping patterns, breastfeeding, relative energy deficiency in sport, postpartum fatigue and thyroid autoimmunity, fear of movement, psychological well-being, and socioeconomic considerations. Undertaking a risk-benefit analysis on a case-by-case basis using clinical reasoning to determine readiness to return-to-running postpartum should incorporate these considerations and their possible interactions, alongside considerations of a musculoskeletal evaluation and graded exercise progression.

Conclusions:

Return-to-running postpartum requires an individualized, whole-systems biopsychosocial approach with graded exercise progression, similar to the management of return to sport following musculoskeletal injuries.

A video abstract for this article is available at:
http://links.lww.com/JWHPT/A51
Pelvic Health Physical Therapy Improves Pelvic Floor Symptoms in Women With Obstetric Anal Sphincter Injury
Authors: Kim Lisa , Weeks Karen , Geynisman-Tan Julia
Published: February 2022

Background:

Following obstetric anal sphincter injuries (OASISs), women commonly report symptoms of pelvic floor dysfunction such as fecal incontinence. Few studies have looked at pelvic health physical therapy (PHPT) as a treatment for women with OASIS and its associated symptoms.

Objectives:

To assess the outcomes of early PHPT on the presence and severity of symptoms in women with OASIS.

Study Design:

Retrospective cohort study.

Methods:

We assessed the records of 70 subjects with third- or fourth-degree OASIS who had undergone clinical evaluation and PHPT in the institution's pelvic health clinic between 2017 and 2019. PHPT assessment focused on pelvic and abdominal muscle strength, neuromuscular control, soft and connective tissue/scar mobility, and functional movement. Outcome measures assessed changes in the Pelvic Floor Distress Inventory-20 (PFDI-20), subjective symptom reports of pelvic floor dysfunction, and manual muscle testing of pelvic floor muscle strength. These changes were calculated using the t test, McNemar's test, and Wilcoxon rank sum test, respectively.

Results:

PHPT started within an average of 6.2 weeks resulted in a reduction across all subjective complaints. Pelvic floor muscle strength improved from an initial Modified Oxford Grading system (MOS) score of 1 (1-2) to 2 (1-3), (P < .01). Subjects who received PHPT within 2 months postpartum had a greater reduction in subjective symptoms than those who started after 2 months (2.4 ±1.7 vs 1.1 ± 1.3, P = .02).

Conclusion:

PHPT intervention is associated with a reduction in subjective complaints reported by women who experienced OASIS in a single tertiary center. Earlier initiation of PHPT may lead to a greater improvement in symptoms.