bluuebunny/crossref_metadata_2025 huggingface dataset:
G‐type Halohydrin Dehalogenases Catalyze Ring Opening Reactions of Cyclic Epoxides with Diverse Anionic Nucleophiles**
Authors: Solarczek Jennifer , Kaspar Felix , Bauer Pia , Schallmey Anett
Published: October 2022

Halohydrin dehalogenases are promiscuous biocatalysts, which enable asymmetric ring opening reactions of epoxides with various anionic nucleophiles. However, despite the increasing interest in such asymmetric transformations, the substrate scope of G‐type halohydrin dehalogenases toward cyclic epoxides has remained largely unexplored, even though this subfamily is the only one known to display activity with these sterically demanding substrates. Herein, we report on the exploration of the substrate scope of the two G‐type halohydrin dehalogenases HheG and HheG2 and a newly identified, more thermostable member of the family, HheG3, with a variety of sterically demanding cyclic epoxides and anionic nucleophiles. This work shows that, in addition to azide and cyanide, these enzymes facilitate ring‐opening reactions with cyanate, thiocyanate, formate, and nitrite, significantly expanding the known repertoire of accessible transformations.
Catalyst‐Free Regio‐ and Diastereoselective Synthesis of Heterocyclic Nucleosides in the Eco‐friendly Solvent 2‐Methyltetrahydrofuran†
Authors: Gu Xiaodong , Du Qingwei , Song Weijian , Wang Jun Joelle
Published: October 2022

Comprehensive Summary

An efficient and practical synthesis of heterocyclic nucleosides is developed by a catalyst‐free highly regioselective and diastereoselective [3+2] annulation of α‐purine‐substituted acrylates with nitrones. The reaction operates with excellent functional group tolerance, very mild reaction conditions, and with the green, sustainable, and eco‐friendly 2‐methyltetrahydrofuran (2‐MeTHF) as solvent. Compared with other reactions of electron‐deficient olefin dipolarophiles with nitrones, different regioselective cycloaddition products were observed in this work. This 1,3‐dipolar cycloaddition reaction gives a series of isoxazolidinyl nucleosides in good to excellent yields with promising applications in biochemistry and medicinal chemistry.
The burden of chronic rhinosinusitis with nasal polyps and its relation to asthma in Finland
Authors: Toppila‐Salmi Sanna , Hällfors Jenni , Aakko Juhani , Mannerström Bettina , Nieminen Kaisa , Telg Gunilla , Lehtimäki Lauri
Published: October 2022

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly associated with asthma. Treatment of CRSwNP includes intranasal and systemic corticosteroids, with non‐responsive patients commonly considered for endoscopic sinus surgery (ESS). This nationwide register‐based study evaluated the incidence, prevalence, and treatment burden of CRSwNP in Finland, and their association with the presence and severity of comorbid asthma.

Methods

Electronic health records of patients diagnosed with CRSwNP between 1.1.2012 and 31.12.2018 in Finnish specialty and primary care were included in the study. The patients were divided into subgroups based on presence, severity, and control of asthma: no asthma, mild to moderate asthma, severe controlled asthma, and severe uncontrolled asthma. A mean cumulative count of ESS was calculated over time per subgroup.

Results

The prevalence of CRSwNP increased from 602.2 to 856.7 patients per 100,000 population between years 2012 and 2019 (p < 0.001). A total of 18,563 patients (59.9% male) had incident CRSwNP between 2012 and 2019, with 27% having asthma, 6% having severe asthma, and 1.5% having severe uncontrolled asthma. In the no asthma, severe controlled asthma, and severe uncontrolled asthma subgroups, systemic corticosteroids were used by 54.1%, 94.9% and 99.3% (p < 0.001), respectively, while the ESS count 3 years post diagnosis was 0.49, 0.68 and 0.80, respectively.

Conclusions

The prevalence of CRSwNP showed a significant increase in the recent decade in Finland. Comorbid asthma, and in particular severe asthma, increased the probability of receiving systemic corticosteroids and undergoing ESS. Thus, improved management of CRSwNP in patients with comorbid asthma is urgently needed.
Screening brain MRI in inflammatory breast cancer: Is it time?
Authors: Dhakal Ajay , Anders Carey K.
Published: October 2022

The study of brain metastasis (BrM) in patients with inflammatory breast cancer (IBC) by Warren et al. that accompanies this editorial has reported a high incidence of BrM and poor survival after BrM diagnosis. The question rises: should we adopt routine brain MRI in patients with IBC for early detection of BrMs and will this make a difference in survival and quality of life of patients? This editorial tries to approach these questions.
Ab Initio Study of H‐Bond Dynamics in Three‐Component Crystals Comprising (DABCOH+)nPolycationic Chains
Authors: Malec Leszek M. , Brela Mateusz Z. , Stadnicka Katarzyna M.
Published: October 2022

In this work, the dynamic character of hydrogen‐bond (H‐bond) networks in two three‐component crystals comprising polycationic chains was described. The first studied system was 1,4‐diazabicyclo[2.2.2]octan‐1‐ium (DABCOH+) sulfamate monohydrate, known for its large negative linear compressibility. The second analyzed material was the newly obtained polar salt co‐crystal: 1,4‐diazabicyclo[2.2.2]octan‐1‐ium sulfamate urea. X‐ray diffraction measurements enabled us to study the H‐bond systems in both crystals using the graph set analysis. Obtained structures served as the initial models for Born‐Oppenheimer molecular dynamics computations. A detailed study of intermolecular interactions and power spectra was conducted. The analysis of time and space correlations between the changes in H‐bonds enabled the detection of proton transfer occurring in both systems at 300 K. Further study of those dynamic phenomena was done using the Energy Decomposition Analysis for selected trajectory fragments. Our work should improve the understanding of dielectric and ferroelectric properties of hybrid organic‐inorganic materials.
Informed consent for psychotherapy: Ethical illusion or clinical reality? A survey about psychotherapists' attitudes and practices in Germany
Authors: Gerke Leonie , Meyrose Ann‐Katrin , Nestoriuc Yvonne
Published: October 2022

Objective

This study aimed to assess clinicians' attitudes and their current clinical practices regarding informed consent for psychotherapy.

Method

A convenience sample of N = 530 clinicians in Germany (n = 418 licensed psychotherapists and n = 112 postgraduate psychotherapy trainees) took part in an online survey.

Results

Most clinicians (84%) reported obtaining informed consent for psychotherapy in their daily routine. However, many psychotherapists felt unsure about satisfactorily fulfilling the legal (63%) and ethical obligations (52%). The two most frequently reported components of information disclosure related to explaining the terms and conditions of psychotherapy (96%) and the psychotherapeutic approach (91%). Providing information about mechanisms of psychotherapy (33%) and the role of expectations (30%) were least practiced. One in five psychotherapists reported not informing clients about potential risks and side effects. A considerable proportion reported concern about inducing anxiety in patients by disclosing information about risks and side effects (52%).

Conclusions

Although obtaining informed consent for psychotherapy seems to be the rule rather than the exception in clinical practice, the quality of its implementation in terms of legal, ethical and clinical demands remains questionable. Training psychotherapists in providing comprehensive informed consent enables informed decision‐making and might have a positive influence on treatment expectations and outcomes.
What is the best anthropometry index to evaluate the risk of metabolic abnormalities in Chinese adults?
Authors: Hu Jun , Jiang Yongbin , Shen Hui , Ding Limin , Xu Xiaopao , Wu Wenjun
Published: October 2022

Aims

Obesity, defined by body mass index (BMI), is a heterogeneous condition with varying metabolic manifestations, and the best index for predicting metabolic abnormalities remains unclear. This study aimed to explore the most suitable anthropometry index for predicting metabolic abnormalities in Chinese adults.

Methods

A cross‐sectional study was conducted using the data obtained from 9517 Chinese adults who underwent physical examination, bioelectrical impedance analysis, and laboratory examinations between March 2018 and March 2022. Participants were further divided into eight subgroups according to age, BMI, and sex. Descriptive statistics were calculated, and the area under the receiver operating characteristic curve and Youden index values were calculated to identify the best predictor of metabolic abnormalities in Chinese adults.

Results

The waist‐to‐height ratio (WHtR) had the largest area under the curve for predicting metabolic abnormalities in men of any age and women aged 18–49 years. However, BMI showed the highest accuracy in predicting metabolic abnormalities in women aged 50 years and older. Based on the highest Youden index, the optimal WHtR threshold was 0.51 in women and 0.53 in men.

Conclusions

The WHtR was the most effective index for predicting metabolic abnormalities in most Chinese adults, whereas BMI showed a higher accuracy only in elderly women. This observation supports WHtR as a novel adiposity marker for screening metabolic abnormalities and shows value for public health practice.
Annual variation in breeding success in boreal forest grouse: Four decades of monitoring reveals bottom‐up drivers to be more important than predation
Authors: Wegge Per , Moss Robert , Rolstad Jørund
Published: October 2022

Knowledge of the temporal variation in reproductive success and its key driving factors is crucial in predicting animal population persistence. Few studies have examined the effects of a range of explanatory factors operating simultaneously on the same population over a long period. Based on 41 years of monitoring (1979–2019), we tested prevailing hypotheses about drivers of annual variation in breeding success in two sympatric species of boreal forest grouse—the capercaillie (Tetrao urogallus) and the black grouse (T. tetrix)—in a 45 km2 boreal forest landscape. From counts in early August, we measured breeding success (chicks/hen) along with potential determining factors. We formulated five main hypotheses on causes of variation (hen condition, chick weather, chick food, predation, demographic characteristics) and derived 13 associated explanatory variables for analysis. We first tested the five hypotheses separately and then used model selection (AICc) to rank the best predictive models irrespective of hypotheses. Lastly, we used path analysis to illuminate potential causal relationships. Barring demographic characteristics, all hypotheses were supported, most strongly for chick food and predation. Among predictor variables, chick food (insect larvae and bilberry fruit crops), vole and fox abundances, the winter‐NAO index, and temperature after hatching, had the strongest effect sizes in both species. Precipitation after hatching had no detectable effect. Model selection indicated bottom‐up factors to be more important than predation, but confounding complicated interpretation. Path analysis suggested that the high explanatory power of bilberry fruiting was due not only to its direct positive effect on chick food quality but also to an indirect positive effect on vole abundance, which buffers predation. The two components of breeding success—proportion of hens with broods and number of chicks per brood—were uncorrelated, the former having the strongest effect. The two components had different ecological correlates that often varied asynchronously, resulting in overall breeding success fluctuating around low to moderate levels. Our study highlights the complexity of key explanatory drivers and the importance of considering multiple hypotheses of breeding success. Although chick food appeared to equal or surpass predation in explaining the annual variation in breeding success, predation may still be the overall limiting factor. Comparative and experimental studies of confounded variables (bilberry fruiting, voles, and larvae) are needed to disentangle causes of variation in breeding success of boreal forest grouse.
Functional traits of riparian trees in the lower Fitzroy River, Western Australia
Authors: Canham Caroline A. , Woods Calum , Setterfield Samantha A. , Veneklaas Erik J. , Freestone Fiona L. , Beesley Leah S. , Douglas Michael M.
Published: October 2022

Riparian trees are critically important for maintaining the ecological function of freshwater ecosystems. Globally, anthropogenic changes to water regimes are impacting the health and distribution of riparian trees. Understanding the physiological constraints on the distribution of riparian tree species in relation to the water regime is essential for informed water resource management that seeks to limit impacts on riparian trees. To fill an identified knowledge gap for the Fitzroy River, a significant river in the wet–dry tropics of north‐western Australia, we used a trait‐based approach to characterise nine common riparian tree species in relation to their distribution along a hydrological gradient. We assessed key functional traits related to drought and flood flows. Leaf mass per unit area (LMA), leaf dry matter content (LDMC), foliar carbon content (% C) and the ratio of carbon to nitrogen (C:N) are broadly related to plant productivity and durability and may reflect resistance to fluvial stress. Traits related to water availability were stem specific density (SSD), mean xylem vessel diameter and xylem vessel density, as well as foliar δ13C which is related to water use efficiency, and leaf osmotic potential at full hydration (π100) as a measure of drought tolerance. We found that π100, δ13C and SSD values reflected species hydrological habitat preferences, with higher δ13C values and lower π100 for species distributed in the drier floodplain habitats, compared with species constrained to the riverbank. Low SSD values for species close to the riverbank may be indicative of aerenchyma tissue in response to flooding. Differences in leaf trait values were primarily attributed to differences between evergreen Myrtaceous and deciduous non‐Myrtaceous species, rather than hydrological habitat preferences. LMA was greatest for the Myrtaceous study species, with deciduous non‐Myrtaceous species associated with wetter habitats having the lowest values. The physiology of riparian trees in northern Australia is not well described for the majority of species. Our study provides insight into plant functional strategies in response to both flooding and drought and is a critical step in understanding plant responses to future water‐take scenarios to support evidence‐based decision making.
Protesting for stability or change? Definitional and conceptual issues in the study of reactionary, conservative, and progressive collective actions
Authors: Thomas Emma F. , Osborne Danny
Published: October 2022

Over the last quarter of a century, social psychological research on collective action has grown exponentially and progressed through four distinct phases. While the first phase showed that identity, efficacy, and injustice motivate the aggrieved to protest on behalf of their ingroup, the second phase acknowledged that protests could involve collaborations between the disadvantaged and their advantaged allies. The third phase of research examined reactionary movements by integrating ideology and acknowledging that advantaged groups can protest to protect or expand their privileged status. The research showcased in this special issue highlights a fourth phase of collective action by illustrating its dialectical nature and recognising the opposing agendas advanced by structurally disadvantaged and advantaged groups. We also advance a two‐dimensional taxonomy differentiating between the goals (Inclusive vs. Exclusive) and societal implications (Challenge vs. Defend the Status Quo) of collective action. In doing so, we provide some of the necessary conceptual and definitional foundations for the next generation of research on collective action and social change.
Morphology, flow dynamics and evolution of englacial conduits in cold ice
Authors: Kamintzis Jayne E. , Irvine‐Fynn Tristram D. L. , Holt Tom O. , Jones John P. P. , Porter Philip R. , Jennings Stephen J. A. , Naegeli Kathrin , Hubbard Bryn
Published: October 2022

Meltwater routing through ice masses exerts a fundamental control over glacier dynamics and mass balance, and proglacial hydrology. However, despite recent advances in mapping drainage systems in cold, Arctic glaciers, direct observations of englacial channels and their flow conditions remain sparse. Here, using terrestrial laser scanning (TLS) surveys of the main englacial channel of cold‐based Austre Brøggerbreen (Svalbard), we map and compare an entrance moulin reach (122 m long) and exit portal reach (273 m long). Analysis of channel planforms, longitudinal profiles, cross‐sections and morphological features reveals evidence of spatial variations in water flow conditions and channel incision mechanisms, and the presence of vadose, epiphreatic and phreatic conditions. The entrance reach, located at the base of a perennial moulin, was characterized by vadose, uniform, channel lowering at annual timescales, evidenced by longitudinal grooves, whereas the exit portal reach showed both epiphreatic and vadose conditions, along with upstream knickpoint migration at intra‐annual timescales. Fine‐scale features, including grooves and scallops, were readily quantified from the TLS point cloud, highlighting the capacity of the technique to inform palaeoflow conditions, and reveal how pulses of meltwater from rainfall events may adjust englacial conduit behaviour. With forecasts of increasing Arctic precipitation in the coming decades, and a progressively greater proportion of glaciers comprising cold ice, augmenting the current knowledge of englacial channel morphology is essential to constrain future glacier hydrological system change.
Numerical analysis of heat transfer and magnetohydrodynamic flow of viscoelastic Jeffery fluid during forward roll coating process
Authors: Ali Fateh , Hou Yanren , Zahid Muhammad , Rana M. A. , Kumam Poom , Sitthithakerngkiet Kanokwan
Published: October 2022

The steady‐state laminar nonisothermal, incompressible viscoelastic fluid flows with the Jeffrey model between two counterrotating (same direction) rolls are studied analytically. The Jeffrey model is reduced to the Newtonian model after some appropriate modifications. The new dimensionless governing equations are acquired through suitable nondimensional values. The lubrication approximation theory is employed for the simplification of emerging equations. The exact expressions for pressure gradient, velocity, temperature, and flow rate are accomplished whereas some quantities of interest such as pressure, coating thickness, power transmitted by rolls to the fluid, and roll separation force are computed numerically by using a numerical method. The influence of emerging parameters such as the ratio of relaxation time to the retardation time , magnetohydrodynamic (MHD) parameter and Brinkman number on velocity profile, temperature profile, pressure gradient, pressure distribution, coating thickness, power input, and force of roll separation are presented numerically in a tabular way and specific outcomes are demonstrated graphically. The MHD acts as a regulatory parameter for various quantities of important interest, such as velocity, coating thickness, and temperature. It is worth noting that the coating thickness decreases as modified capillaries number is increased.
Making colonoscopy‐based screening more efficient: A “gateopener” approach
Authors: Heisser Thomas , Cardoso Rafael , Niedermaier Tobias , Hoffmeister Michael , Brenner Hermann
Published: October 2022

Screening colonoscopy for early detection and prevention of colorectal cancer (CRC) is mostly used inefficiently. Here, we assessed the potential of an innovative approach to colonoscopy‐based screening, by use of a single, low threshold fecal immunochemical test (FIT) as a “gateopener” for screening colonoscopy. Using COSIMO, a validated simulation model, we modeled scenarios including either direct invitation to screening colonoscopy or an alternative approach involving mailing a single (“gateopener”) FIT along with an invitation to colonoscopy contingent on a FIT value above a low threshold yielding a 50% positivity rate (ie, every other pretest will be positive). Under plausible assumptions on screening offer adherence, we found that such “gateopener screening” (use of screening colonoscopy contingent on a positive, low threshold gateopener FIT) approximately doubled cancer detection rates vs conventional screening. In those spared from screening colonoscopy due to a negative gateopener FIT pretest, numbers needed to screen were 10‐times higher vs those for individuals with a positive FIT, peaking in >2000 and >3800 (hypothetically) needed colonoscopies to detect one case of cancer in men and women, respectively. Gateopener screening resulted in 42%‐51% and 59%‐65% more prevented CRC cases and deaths, respectively. In summary, by directing colonoscopy capacities to those most likely to benefit, offering screening colonoscopy contingent on a “gateopener” low‐threshold FIT would substantially enhance efficiency of colonoscopy screening.
A Vision for Universal and Standardized Access to Systems Competency Education
Authors: Singam Caitlyn A. K.
Published: October 2022

The interdisciplinary nature of systems engineering inherently means that the concept of a systems engineer is variable, requiring several types of expertise depending on the application sector and knowledge domain the individual is working in. However, regardless of industry or specialty, systems engineers are all unified by proficiency in a core set of fundamental competencies that allow them to understand and holistically work with systems.

These systems thinking and systems engineering competencies are applicable by being interdisciplinary and are well‐suited to an increasingly globalized and interconnected world. However, views of systems thinking and systems engineering competencies as non‐essential supplementary skills rather than foundational ones have meant that systems thinking and systems engineering concepts are not generally included in science, technology, engineering, arts, and mathematics (STEAM) curricula until late in the educational pathway and are not always presented in a standardized manner. Consequently, under the current approach to systems thinking and systems engineering, not all individuals who can benefit from systems thinking and systems engineering education have access to it. Those who do often face substantial variability in the quality of their educational experiences.

This article discusses existing issues relating to systems thinking and systems engineering competency education, as well as the efforts of the INCOSE SySTEAM Initiative towards addressing those issues and facilitating the integration of systems thinking and systems engineering competencies into STEAM curricula at all levels of education. Furthermore, this article presents a guiding philosophy for promoting universal and standardized access to systems competency education.
Probing the effects of matrix‐derived microcarrier composition on human adipose‐derived stromal cells cultured dynamically within spinner flask bioreactors
Authors: Kornmuller Anna , Cooper Tyler T. , Jani Ammi , Lajoie Gilles A. , Flynn Lauren E.
Published: October 2022

Recognizing the cell‐instructive capacity of the extracellular matrix (ECM), this study investigated the effects of expanding human adipose‐derived stromal cells (hASCs) on ECM‐derived microcarriers fabricated from decellularized adipose tissue (DAT) or decellularized cartilage tissue (DCT) within spinner flask bioreactors. Protocols were established for decellularizing porcine auricular cartilage and electrospraying methods were used to generate microcarriers comprised exclusively of DAT or DCT, which were compositionally distinct, but had matching Young's moduli. Both microcarrier types supported hASC attachment and growth over 14 days within a low‐shear spinner culture system, with a significantly higher cell density observed on the DCT microcarriers at 7 and 14 days. Irrespective of the ECM source, dynamic culture on the microcarriers altered the expression of genes and proteins associated with cell adhesion and ECM remodeling. Label‐free mass spectrometry analysis showed upregulation of proteins associated with cartilage development and ECM in the hASCs expanded on the DCT microcarriers. Based on Luminex analysis, the hASCs expanded on the DCT microcarriers secreted significantly higher levels of IL‐8 and PDGFAA, supporting that the ECM source can modulate hASC paracrine factor secretion. Finally, the hASCs expanded on the microcarriers were extracted for analysis of adipogenic and chondrogenic differentiation relative to baseline controls. The microcarrier‐cultured hASCs showed enhanced intracellular lipid accumulation at 7 days post‐induction of adipogenic differentiation. In the chondrogenic studies, a low level of differentiation was observed in all groups. Future studies are warranted using alternative cell sources with greater chondrogenic potential to further assess the chondro‐inductive properties of the DCT microcarriers.
Stochastic kinetic study of protein aggregation and molecular crowding effects of Aβ40 and Aβ42
Authors: Bridstrup John , Yuan Jian‐Min , Schreck John S.
Published: October 2022

Two isoforms of β‐amyloid peptides, Aβ40 and Aβ42, differ from each other only in the last two amino acids, IA, at the end of Aβ42. They, however, differ significantly in their ability in inducing Alzheimer's disease (AD). The rate curves of fibril growth of Aβ40 and Aβ42 and the effects of molecular crowding have been measured in in vitro experiments. These experimental curves, on the other hand, have been fitted in terms of rate constants for elementary reaction steps using rate equation approaches. Several sets of such rate parameters have been reported in the literature. Employing a recently developed stochastic kinetic method, implemented in a browser‐based simulator, popsim, we study to reveal the differences in the kinetic behaviors implied by these sets of rate parameters. In particular, the stochastic method is used to distinguish the kinetic behaviors between Aβ40 and Aβ42 isoforms. As a result, we make general comments on the usefulness of these sets of rate parameters.
Young geniuses versus old masters: Two different trajectories of individual knowledge bases in the innovation process
Authors: Zhu Siwei , Morkan Baris , Yan Zhipeng
Published: October 2022

Knowledge depth and knowledge breadth, the two dimensions of individual knowledge bases, are the most fundamental sources of innovation. Following a mixed‐method approach, we collect data from top chemical scientists in the R&D department of a leading US oil and gas company and investigate how individuals leverage their knowledge bases in the innovation process. In the qualitative study, we develop a conceptual framework with the two‐stage innovation process and label two distinct groups of individuals as “Young Geniuses” with high knowledge depth and “Old Masters” with high knowledge breadth. In the quantitative study, our analysis shows two different trajectories toward the innovation process: the negative impact of knowledge depth on early stage knowledge combinations for Young Geniuses occurs extremely early; the diminishing return of knowledge breadth on late‐stage commercialization for Old Masters occurs very late. Our study further analyzes the interaction effect of knowledge breadth for knowledge depth and provides practical implications for managers; in particular, inventors who better comprehend the timing of switching knowledge development can navigate the innovation process to achieve fruitful outcomes.
Publicly available framework for simulating and experimentally validating clinical PET systems
Authors: O'Briain Teaghan B. , Uribe Carlos , Sechopoulos Ioannis , Michel Christian , Bazalova‐Carter Magdalena
Published: October 2022

Background: Monte Carlo (MC) simulations are a powerful tool to model medical imaging systems. However, before simulations can be considered the ground truth, they have to be validated with experiments.

Purpose: To provide a pipeline that models a clinical positron emission tomography (PET)/CT system using MC simulations after extensively validating the results against experimental measurements.

Methods: A clinical four‐ring PET imaging system was modeled using Geant4 application for tomographic emission (v. 9.0). To validate the simulations, PET images were acquired of a cylindrical phantom, point source, and image quality phantom with the modeled system and the simulations of the experimental procedures. For the purpose of validating the quantification capabilities and image quality provided by the simulation pipeline, the simulations were compared against the measurements in terms of their count rates and sensitivity as well as their image uniformity, resolution, recovery coefficients (RCs), coefficients of variation, contrast, and background variability.

Results: When compared to the measured data, the number of true detections in the MC simulations was within 5%. The scatter fraction was found to be 30.0% ± 2.2% and 28.8% ± 1.7% in the measured and simulated scans, respectively. Analyzing the measured and simulated sinograms, the sensitivities were found to be 8.2 and 7.8 cps/kBq, respectively. The fraction of random coincidences were 19% in the measured data and 25% in the simulation. When calculating the image uniformity within the axial slices, the measured image exhibited a uniformity of 0.015 ± 0.005, whereas the simulated image had a uniformity of 0.029 ± 0.011. In the axial direction, the uniformity was measured to be 0.024 ± 0.006 and 0.040 ± 0.015 for the measured and simulated data, respectively. Comparing the image resolution, an average percentage difference of 2.9% was found between the measurements and simulations. The RCs calculated in both the measured and simulated images were found to be within the EARL ranges, except for that of the simulation of the smallest sphere. The coefficients of variation for the measured and simulated images were found to be 12% and 13%, respectively. Lastly, the background variability was consistent between the measurements and simulations, whereas the average percentage difference in the sphere contrasts was found to be 8.8%.

Conclusion: The clinical PET/CT system was modeled and validated to provide a simulation pipeline for the community. The pipeline and the validation procedures have been made available (https://github.com/teaghan/PET_MonteCarlo).
Imaging of neuralgic amyotrophy in the acute phase
Authors: Ripellino Paolo , Arányi Zsuzsanna , van Alfen Nens , Ventura Elisa , Peyer Anne‐Kathrin , Cianfoni Alessandro , Gobbi Claudio , Pedrick Emily , Sneag Darryl Brett
Published: October 2022

Introduction/Aims

Hourglass‐like constrictions (HGCs) occur in neuralgic amyotrophy (NA), but the earliest time at which they can be recognized by imaging is poorly understood. We aimed to determine the prevalence of abnormal imaging findings in the acute phase of NA.

Methods

Magnetic resonance neurography (MRN) and high‐resolution ultrasound (US) examinations were performed at five sites. The investigation included 39 patients with acute NA who underwent imaging within 31 days of symptom onset. Correlation between imaging and electromyography (EMG) findings was measured.

Results

US was performed in 29 patients and MRN in 23; 16 patients underwent US only, 10 MRN only, and 13 had both. US and MRN showed nerve abnormalities within 1 mo from NA onset in 90% of patients. HGCs were found in 74% (29/39) of the patients: 4 within 1 wk, 8 within 2 wk, 5 within 3 wk, and 12 within 4 wk. The earliest HGC on US was found within 12 h, and on MRN within 3 days from symptom onset. MRN demonstrated a denervation edema pattern of affected muscles in 91% of the patients. The shortest time to observe an edema pattern on MRN was 8 days. EMG was performed in 30 patients and revealed fibrillation potentials in affected muscles in 22 (73%). A denervation edema pattern on MRN was significantly associated with the presence of HGCs both on MRN and US, and with fibrillation potentials on EMG.

Discussion

In the early phase of NA, US and MRN are useful diagnostic techniques for demonstrating nerve abnormalities.
Assessment of clinical skills in electrodiagnostic medicine
Authors: Becker Benjamin , London Zachary N.
Published: October 2022

See article on pages 671–678 in this issue.
Associations of neuralgic amyotrophy with COVID‐19 vaccination: Disproportionality analysis using the World Health Organization pharmacovigilance database
Authors: Kim Jee‐Eun , Park Jin , Min Young Gi , Hong Yoon‐Ho , Song Tae‐Jin
Published: October 2022

Introduction/Aims

There are limited studies on the association of COVID‐19 vaccination with neuralgic amyotrophy (NA). Therefore, we evaluated the association between COVID‐19 vaccination and the occurrence of NA.

Methods

We explored unexpected safety signals for NA related to COVID‐19 vaccination through disproportionality analysis using VigiBase, the World Health Organization's pharmacovigilance database.

Results

On October 15, 2021, 335 cases of NA were identified in the database. The median time to onset of NA after vaccination was around 2 weeks. A significant signal of disproportionality of NA was observed for the ChAdOx1 nCoV‐19 vaccine (AstraZeneca) (information component [IC]025 = 0.33, reporting odds ratio [ROR]025 = 1.30) and two mRNA‐based COVID‐19 vaccines (BNT162b2 [Pfizer and BioNTech] and mRNA‐1273 [Moderna]) (IC025 = 1.74, ROR025 = 3.82) compared with the entire database. However, when compared with influenza vaccines, we did not detect any signal of disproportionality of NA for both the ChAdOx1 nCoV‐19 vaccine (IC025 = −2.71, ROR025 = 0.05) and mRNA‐based COVID‐19 vaccines (IC025 = −1.38, ROR025 = 0.13).

Discussion

A weak association was observed between NA and COVID‐19 vaccines. However, the risk did not surpass that of influenza vaccines.
Clinical and neurophysiological biomarkers of disease progression in amyotrophic lateral sclerosis
Authors: Hannaford Andrew , Byth Karen , Pavey Nathan , Henderson Robert D. , Mathers Susan , Needham Merrilee , Schultz David , Menon Parvathi , Kiernan Matthew C. , Vucic Steve
Published: October 2022

Introduction/Aims

Rate of disease progression (ΔFS), measured as change in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS‐R) and body mass index (BMI), are predictors of survival in amyotrophic lateral sclerosis (ALS). Our aim in this study was to assess the utility of these clinical biomarkers along with neurophysiological measures, such as the split hand index (SI), in monitoring disease progression.

Methods

Clinical trial data were collected from 107 patients recruited into the Tecfidera in ALS trial. The prognostic utility of clinical and neurophysiological measures, including ΔFS, BMI, SI, and neurophysiological index (NPI), were assessed cross‐sectionally and longitudinally (40 weeks). The outcome measures of disease severity and progression included: (i) ALSFRS‐R score; (ii) Medical Research Council (MRC) score; and (iii) forced vital capacity and sniff nasal inspiratory pressure.

Results

Fast‐progressor ALS patients (ΔFS ≥1.1) exhibited significantly lower ALSFRS‐R and total MRC scores at baseline. A baseline ΔFS score ≥1.1 was associated with a greater reduction in ALSFRS‐R (P = .002) and MRC (P = .002) scores over 40 weeks. Baseline BMI <25 was also associated with faster reduction of ALSFRS‐R and MRC scores. SI and NPI were associated with disease severity at baseline, but not with subsequent rate of disease progression.

Discussion

Implementation of the assessed clinical and neurophysiological biomarkers may assist in patient management and stratification into clinical trials.
Motor unit recruitment and firing rate at low force of contraction
Authors: Nandedkar Sanjeev D. , Barkhaus Paul E. , Stålberg Erik V.
Published: October 2022

Introduction/Aims

A prevailing concept of motor unit (MU) recruitment used for calculating recruitment ratio (RR) suggests a progressive linear increase in firing rate (FR). The objective of this study is to assess its validity.

Methods

Concentric needle electromyography (EMG) recordings were made in normal muscle and abnormal muscle of patients with neurogenic findings. Signals recorded at low force were visually decomposed to study MU FR at onset, recruitment of a second MU, and recruitment of more MUs with further increases in force.

Results

We observed one to six MUs discharging at a rate < 15 Hz in normal muscles at low force. The MU FR was 5–8 Hz at onset. With increasing force, FR increased by 3–5 Hz and then idled at <15 Hz while other MUs were recruited. The recruitment frequency (RF) and RR had low sensitivity and were abnormal mainly in moderately to severely weak muscles.

Discussion

Our data are consistent with FR analysis results described by other investigators. It does not support a progressive linear increase in MU FR with recruitment. A revised model for MU recruitment at low effort during gradual increase in force is presented. On subjective assessment, the FR of the fastest firing MU can help detect MU loss in neurogenic processes.
Instrumental variable‐based multi‐innovation gradient estimation for nonlinear systems with scarce measurements
Authors: Xia Huafeng , Xu Sheng , Miao Xinghua , Cao Jian
Published: October 2022

This article considers the identification problems of nonlinear systems with scarce measurements by using the instrumental variable technique. When the product of the instrumental matrix and the information matrix is a nonsingular matrix and the weak persistent excitation condition about the instrumental vector is true, the obtained parameter estimates can be unbiased consistent estimates. The key is how to choose the instrumental variables. Difficulty arises in that the system outputs are unavailable. By applying the negative gradient search, a recursive instrumental variable‐based gradient algorithm is derived to estimate the parameters of the nonlinear systems with missing observed data. Moreover, the multi‐innovation identification theory is introduced to further improve the parameter estimation accuracy. The simulation results illustrate that the proposed methods are effective.
pH stimuli‐responsive and fouling resistance PES membrane fabricated by using photochromic spiropyran and spironaphthoxazine nanofillers for pesticide removal
Authors: Gholami Foad , Zinadini Sirus , Zinatizadeh Ali Akbar , Sanjabi Samira , Mahdavian Ali Reza , Samari Mahya , Vatanpour Vahid
Published: October 2022

New fouling resistance and stimulus–responsive nanofiltration membranes were fabricated by adding photochromic spiropyran (SPO) and spironaphthoxazine (SNO) nanofillers to the polyethersulfone (PES) matrix via the phase inversion method. The effect of SPO and SNO, as novel photoresponsive molecule nanofillers, were evaluated in terms of membrane morphology, porosity, wettability, pure water flux (PWF), antifouling resistance, and stimulus–responsive properties. All the modified membranes indicated better performance compared to the bare PES. The membrane PWF was notably enhanced from 7.7 kg/m2h for the bare PES up to 18.68 and 20.58 kg/m2h for the 0.1 wt.% SPO and SNO blended membranes, respectively. Also, the 0.1 wt.% of SNO‐based PES membrane indicated the best flux recovery ratio compared to the other membranes. The photo stimulus–responsive assessment showed a color change for both SPO and SNO photochromic in membranes. In the case of variable effect investigation, the response surface methodology at three levels (pressure: 4, 5, 6 bar and flow rate: 50, 100, and 150 L/h) was applied. A suitable flux (23.39 kg/m2 h) and high removal efficiency (more than 90%) was achieved at optimum conditions. Also, the modified membranes by photochromic materials were sensitive to environmental variables such as acidic and alkaline conditions by changing their color.
Posttraumatic growth levels of healthcare workers in two periods with different intensities of COVID‐19 pandemic
Authors: Yılmaz‐Karaman İmran Gökçen , Yastıbaş‐Kaçar Cennet , Ece İnce Ferda
Published: October 2022

The COVID‐19 pandemic threatens health‐care workers' (HCW) mental health and well‐being. Although traumatic life events may result in psychiatric disorders, occasionally they give rise to positive changes, such as post‐traumatic growth. Accordingly, the present study evaluated the traumatic stress, anxiety, and depression levels of HCWs and their post‐traumatic growth levels during the pandemic. In addition, the study aimed to assess the changes in psychological outcomes during the pandemic. For this aim, the data were collected in two different periods. The first data‐collection period was between May and July 2020, and the second period started in November 2020 and ended in January 2021. The sociodemographic data form, Impact of Events Scale‐Revised (IES‐R), Generalized Anxiety Disorder‐7 (GAD‐7), Patient Health Questionnaire‐9 (PHQ‐9), and Post‐traumatic Growth Inventory (PTGI) were used to collect data. Sixty‐six HCWs participated in the study. No significant differences appeared between the baseline scores and 6‐month follow‐up in the depression, anxiety, and traumatic stress levels of HCWs. Furthermore, the PTGI scores decreased significantly over time. Although the change in the psychological distress scores was not statistically significant, the depression and post‐traumatic stress scores increased over time. Previous research specified an inverse‐parabolic relationship between traumatic stress and PTGI. Our results support previous research; as the exposure to the stressors continues, individual traumatic stress levels increase, psychiatric disorders become frequent, and affirmative changes (like post‐traumatic growth) decline.
Risk factors and outcomes of severe hypoglycaemia requiring hospital admission: a retrospective study
Authors: Galea Alison , Farrugia Stephanie , Calleja Neville , Coppini David V
Published: October 2022

This is a retrospective study intended to determine the prevalence of severe hypoglycaemia requiring admission to Mater Dei Hospital from January to December 2018. We identified risk factors associated with hospital admission and conducted a survival analysis of the cohort.

All patients admitted with diabetes and hypoglycaemia were identified by means of hospital admission database, clinical notes, discharge summaries and iSOFT clinical manager. A Cox regression model and a multivariate analysis were utilised to study survival analysis at one year after admission in relation to management strategies, comorbidity and length of hospital stay.

A total of 167 episodes (0.77%) of hypoglycaemia admissions satisfying inclusion criteria were identified out of 21,589 medical admissions. Type 2 diabetes (T2DM) was present in 154 patients (92.2%), mean age was 71.5 years (SD 15.5) and mean length of stay was 4.4 days (SD 5.3). A survival analysis showed a negative association with a higher Charlson Comorbidity Index (CCI) score (95% CI 1.132–1.516, p<0.05), Parkinson's disease (95% CI 0.078–0.670, p<0.05) and residing in care homes (95% CI 0.274–0.982, p<0.05). Length of stay was related to a poor CCI score (95% CI 0.251–0.967), peripheral vascular disease (95% CI ‐4.658–0.764), and malignancy (95% CI ‐5.438–0.205). There seemed to be no correlation between different diabetes treatment regimens and length of hospital stay or survival.

These findings show a strong link between hypoglycaemia, decreased survival and increased frailty in elderly patients with type 2 diabetes. This study highlights a need for better education and less stringent glycaemic targets for vulnerable patients. Copyright © 2022 John Wiley & Sons.
Stacked antiaromaticity in the π‐congested space between the aromatic rings in the anthracene dimer
Authors: Nishiuchi Tomohiko , Makihara Yuta , Kishi Ryohei , Sato Hiroyasu , Kubo Takashi
Published: October 2022

Substances containing two π‐congested aromatic systems are attractive targets in synthetic studies as well as efforts designed to explore the unique properties that originate from π‐congestion. Since the time of the computational studies by Schleyer and Warner, the concept of stacked aromaticity created by the encounter of two antiaromatic rings has received much attention. A structure containing π‐congestion between two antiaromatic norcorrole rings was prepared by Shinokubo et al. In contrast, questions about what happens when two aromatic rings are closely stacked have remained unanswered. Specifically, the electronic consequences of stacking of two aromatic π‐conjugated systems have not been fully evaluated. To the best of our knowledge, only one computational study has been performed by Herges, the results of which suggest that [2.2]paracyclophane, possessing short distance (<3.00 Å) between two aromatic ring planes, has a paratropic ring current between two the benzene rings. This observation is consistent with the conclusion that stacked antiaromaticity exists within the π‐congested space between aromatic rings. Herein, we investigated the stacked antiaromaticity of highly π‐congested anthracene dimers using anthracenophane, which possesses a short interplane carbon–carbon distance of ca. 2.80 Å. The absorption spectrum of this substance contains a weak broad band from 450 to 550 nm that is attributed to the HOMO–LUMO transition. These properties exist in planar cyclooctatetraene derivatives that have 8π‐electron antiaromaticity. The results of nucleus‐independent chemical shift and anisotropy of the induced current density calculations indicate that a relatively weak antiaromatic character exists between the central six‐membered rings of the two anthracene moieties in anthracenophane. In addition, an attempt to enhance the stacked antiaromaticity of anthracenophane using pressure to enhance π‐congestion was unsuccessful.
Intrinsic protein disorder and conditional folding in AlphaFoldDB
Authors: Piovesan Damiano , Monzon Alexander Miguel , Tosatto Silvio C. E.
Published: October 2022

Intrinsically disordered regions (IDRs) defying the traditional protein structure–function paradigm have been difficult to analyze. The availability of accurate structure predictions on a large scale in AlphaFoldDB offers a fresh perspective on IDR prediction. Here, we establish three baselines for IDR prediction from AlphaFoldDB models based on the recent CAID dataset. Surprisingly, AlphaFoldDB is highly competitive for predicting both IDRs and conditionally folded binding regions, demonstrating the plasticity of the disorder to structure continuum.