bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID‐19 in the hotspot of Metropolitan Detroit: A multi‐faceted health system experience
Authors: Gifford Linda , Johnson Christine C. , Haque Nadia , Passalacqua Karla D. , Swiderek Jennifer , Kalkanis Steven
Published: December 2021

Health systems were abruptly plunged into a crisis as SARS‐CoV‐2 exploded into a pandemic in spring 2020. In March‐April 2020, Metropolitan Detroit was a US “hotspot.” As a large health system with five hospitals and two behavioural health inpatient facilities, a health insurance company, a medical group and physician network, and 41 ambulatory clinics normally hosting over 10,000 daily patient encounters, the Henry Ford Health System deployed numerous strategies in the management of this upheaval. As hospitals and Emergency Departments were inundated with COVID‐19 patients, other services and activities needed to shut down as state‐mandated policies were promulgated, new internal and external communication networks established, and management of employees and resources such as ventilators, ICU beds, personal protective equipment, and laboratory supplies became critical challenges. We describe herein the system‐wide strategies implemented and lessons learned in the operation of a health system in the initial throes of a global pandemic.
An update on hydroxyapatite/collagen composites: What is there left to say about these bioinspired materials?
Authors: Veiga Anabela , Castro Filipa , Rocha Fernando , Oliveira Ana L.
Published: December 2021

Hydroxyapatite (HAp)/collagen‐based composite materials have been a constant in the development of bioinspired materials for bone tissue engineering. The most fundamental research works focus on combining HAp, due to its chemical similarity with the mineral component of bones, and collagen, which is the most abundant protein in the body. Modern studies have explored different two‐dimensional (2D) and 3D structures, in order to obtain biomaterials with specific physicochemical, mechanical, and biological characteristics that can be applied in distinct biomedical applications. However, as there is already so much work developed with these materials, it is crucial to question: what can still be done? What is the importance of current know‐how for the future of bioinspired materials? In this paper we intend to review and update the available methodologies to synthesize HAp/collagen composites, along with their characteristics. In addition, the future of these materials in terms of applications and their potential as a cutting‐edge technology is discussed.
MicroRNA‐34a in coronary heart disease: Correlation with disease risk, blood lipid, stenosis degree, inflammatory cytokines, and cell adhesion molecules
Authors: Li Hefei , Chen Mingchao , Feng Qiang , Zhu Lin , Bai Zhichao , Wang Boya , Guo Zhangli , Hou Aijun , Li Hui
Published: December 2021

Background

MicroRNA‐34a (miR‐34a) plays an essential role in regulating blood lipid, inflammation, cell adhesion molecules, and atherosclerosis, the latter factors are closely involved in the etiology of coronary heart disease (CHD). However, the clinical value of miR‐34a in CHD patients' management is rarely reported. Hence, this study aimed to assess the correlation of miR‐34a with disease risk, blood lipid, coronary artery stenosis, inflammatory cytokines, and cell adhesion molecules of CHD.

Methods

A total of 203 CHD patients and 100 controls were recruited in this study, then their plasma samples were collected to detect the miR‐34a by reverse transcription quantitative polymerase chain reaction. Furthermore, serum samples from CHD patients were obtained for inflammatory cytokines and cell adhesion molecule measurement by enzyme‐linked immunosorbent assay.

Results

MiR‐34a was elevated in CHD patients compared to controls (p < 0.001) and it disclosed a good diagnostic value of CHD (area under curve: 0.899, 95% confidence interval: 0.865–0.934). Besides, miR‐34a positively correlated with triglyceride (p < 0.001), total cholesterol (p = 0.022) and low‐density lipoprotein cholesterol (p = 0.004), but not with high‐density lipoprotein cholesterol (p = 0.110) in CHD patients. Moreover, miR‐34a associated with Gensini score in CHD patients (p < 0.001). As to inflammation‐related indexes and cell adhesion molecules, MiR‐34a expression was positively linked with C‐reactive protein (p < 0.001), tumor necrosis factor alpha (p = 0.005), interleukin (IL)‐1β (p = 0.020), IL‐17A (p < 0.001), vascular cell adhesion molecule‐1 (p < 0.001), and intercellular adhesion molecule‐1 (p = 0.010) in CHD patients, but not with IL‐6 (p = 0.118) and IL‐10 (p = 0.054).

Conclusion

MiR‐34a might serve as a biomarker in assistance of diagnosis and management of CHD.
Clinical study of autoantibodies in type 1 diabetes mellitus children with ketoacidosis or microalbuminuria
Authors: Zhang Mingying , Wang Xinhui , Wang Rui , Shu Jianbo , Zhi Xiufang , Gu Chunyu , Pu Linjie , Cai Chunquan , Yang Wei , Lv Ling
Published: December 2021

Aims

The study aimed to investigate the value of autoantibodies in predicting the risk of ketoacidosis or microalbuminuria in children with type 1 diabetes mellitus.

Methods

Clinical data and laboratory indicators of 80 patients with type 1 diabetes admitted to the Department of Endocrinology in Tianjin Children's Hospital, from June 2017 to March 2019, were retrospectively analyzed. The patients were divided into two groups: diabetes without ketoacidosis group (n = 20) and diabetes with ketoacidosis group (n = 60). The differences in general data, laboratory test indexes, and autoantibodies between the two groups were analyzed. Finally, ROC curves and multivariate logistic regression analysis were used to explore the value of autoantibodies in patients with ketoacidosis or microalbuminuria.

Results

A total of 80 children with type 1 diabetes were assessed, including 35 boys and 45 girls, ranging in age from 10 months to 15 years. The concentration of GADA, IA2A, and ZnT8A was not statistically different between the two groups, but the positive rate of ZnT8A was statistically significant (p = 0.038) and had a diagnostic value for the occurrence of ketoacidosis (p = 0.025). ZnT8A‐positive patients had a higher titer of IA2A and a more frequent prevalence of GADA and IA2A than ZnT8A‐negative patients (p < 0.01). In multivariate logistic regression analyses, the presence of positive ZnT8A was associated with a higher risk of microalbuminuria independent of age, sex, and BMI (OR = 4.184 [95% CI 1.034~16.934], p = 0.045).

Conclusions

The positive ZnT8A had diagnostic value for ketoacidosis in children with type 1 diabetes and had the highest specificity among the three kinds of autoantibodies. Moreover, ZnT8A positivity was related to a higher titer of IA2A and more frequent occurrence of multiple diabetes‐related autoantibodies. Besides, the presence of positive ZnT8A was an independent risk factor of microalbuminuria in children with type 1 diabetes. Therefore, we can infer that positive ZnT8A may be related to ketoacidosis and microalbuminuria, accelerating the progression of T1DM.
Process analytical technology as key‐enabler for digital twins in continuous biomanufacturing
Authors: Schmidt Axel , Helgers Heribert , Lohmann Lara Julia , Vetter Florian , Juckers Alex , Mouellef Mourad , Zobel‐Roos Steffen , Strube Jochen
Published: December 2021

Over the last few years rapid progress has been made in adopting well‐known process modeling techniques from chemicals to biologics manufacturing. The main challenge has been analytical methods as engineers need quantitative data for their workflow. Industrialization 4.0, Internet of Things, artificial intelligence and machine learning activities up to big data analysis have taken their share in solving fundamental problems like component‐ or at least group‐specific evaluation of spectroscopic data. Besides, concerning inline analytics methods included in process analytical technology concepts the key technology has been the generation of decisive validated digital twins based on process models. This review aims to summarize the methodology to achieve a holistic understanding of process models, control and optimization by means of digital twins using the example of recent work published in this field. © 2021 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
The interface region between articular cartilage and bone by μMRI and PLM at microscopic resolutions
Authors: Badar Farid , Xia Yang
Published: December 2021

This dual‐modality microscopic imaging study quantifies the interface region between the noncalcified cartilage and the subchondral bone plate, which includes the deep portion of the noncalcified articular cartilage and the zone of calcified cartilage (ZCC). This interface region is typically not visible in routine MRI but becomes visible in MRI with the application of an ultra‐short echo time (UTE) sequence. A number of cartilage‐bone blocks from a well‐documented canine humeral head were harvested for imaging by microscopic MRI (μMRI) and PLM (polarized light microscopy). In μMRI, T2 anisotropic images were acquired by 2D gradient‐echo, magnetization‐prepared spin‐echo and UTE sequences at the 0° and 55° (the magic angle) orientations at 11.7 μm/pixel resolution. In PLM, quantitative optical retardation (nm) and collagen orientation (°) were mapped from the thin sections from the same μMRI specimens at 0.5–2 μm pixel resolutions. The orientational and organizational architecture of the collagen matrix in this interface region was quantified and correlated between the complementary imaging. The magic angle effect as seen in the noncalcified cartilage was statistically confirmed in ZCC in μMRI, which was further supported by quantitative PLM. With an enhanced understanding of the tissue properties in this important interface region, it will potentially be possible to monitor the changes of this tissue region which is instrumental to the initiation and development of osteoarthritis and other joint diseases.
Secretion of pro‐angiogenic extracellular vesicles during hypoxia is dependent on the autophagy‐related protein GABARAPL1
Authors: Keulers Tom G. , Libregts Sten F. , Beaumont Joel E.J. , Savelkouls Kim G. , Bussink Johan , Duimel Hans , Dubois Ludwig , Zonneveld Marijke I. , López‐Iglesias Carmen , Bezstarosti Karel , Demmers Jeroen A. , Vooijs Marc , Wauben Marca , Rouschop Kasper M.A.
Published: December 2021

Tumour hypoxia is a hallmark of solid tumours and contributes to tumour progression, metastasis development and therapy resistance. In response to hypoxia, tumour cells secrete pro‐angiogenic factors to induce blood vessel formation and restore oxygen supply to hypoxic regions. Extracellular vesicles (EVs) are emerging as mediators of intercellular communication in the tumour microenvironment. Here we demonstrate that increased expression of the LC3/GABARAP protein family member GABARAPL1, is required for endosomal maturation, sorting of cargo to endosomes and the secretion of EVs. Silencing GABARAPL1 results in a block in the early endosomal pathway and impaired secretion of EVs with pro‐angiogenic properties. Tumour xenografts of doxycycline inducible GABARAPL1 knockdown cells display impaired vascularisation that results in decreased tumour growth, elevated tumour necrosis and increased therapy efficacy. Moreover, our data show that GABARAPL1 is expressed on the EV surface and targeting GABARAPL1+EVs with GABARAPL1 targeting antibodies results in blockade of pro‐angiogenic effects in vitro. In summary, we reveal that GABARAPL1 is required for EV cargo loading and secretion. GABARAPL1+EVs are detectable and targetable and are therefore interesting to pursue as a therapeutic target.
Safety and early efficacy of endoscopic sleeve gastroplasty (ESG) for obesity in a multi‐ethnic Asian population in Singapore
Authors: Asokkumar Ravishankar , Lim Chin Hong , Tan Ai Shan , Lee Phong Ching , Eng Alvin , Tan Jeremy , Lopez‐Nava Gontrand , Ganguly Sonali , Chang Jason , Khor Christopher
Published: December 2021

Background and Aim

Endoscopic sleeve gastroplasty (ESG) is an alternative nonsurgical treatment option for obesity. However, most studies on the utility and efficacy of ESG are derived from the Western population. It is unknown if ESG elicits similar results in Asians with different fat distribution, sociocultural customs, and dietary practices. Our study aims to assess the safety and efficacy of ESG among a multi‐ethnic Asian population.

Methods

We reviewed 35 patient records who underwent primary ESG for obesity at our unit. We followed a U‐shaped suture pattern. Our primary outcome was to assess technical feasibility and safety. The secondary outcome was to determine the percentage total body weight loss (TBWL) at the last follow‐up.

Results

The mean ± SD age and body mass index were 43.6 ± 11.3 years and 34 ± 4.9 kg/m2, respectively. The majority were female (57%) and of Chinese ethnicity (51%). The procedure was technically successful in all patients. We used an average of five sutures (range, 4–7), and the mean ± SD procedure time was 65 ± 10 min. No major complications occurred, and the average length of stay was 1 day. Twenty‐one patients completed 3 months of follow‐up, and 10 patients 6 months. The mean ± SD TBWL at 3 and 6 months were 14.5 ± 4.8% and 16.2 ± 4.9%, respectively. We observed improvement in diabetes mellitus (87%), fatty liver (86%), and hypertension (58%) during the follow‐up.

Conclusion

ESG is a safe and effective option for promoting weight loss in a multi‐ethnic Asian population. ESG‐induced weight loss may improve obesity‐related comorbidities.
Post‐endoscopic retrograde cholangiopancreatography pancreatitis assessed using criteria for acute pancreatitis
Authors: Suzuki Azumi , Uno Koji , Nakase Kojiro , Mandai Koichiro , Endoh Bunji , Chikugo Koki , Kawakami Takumi , Suzuki Takahiro , Nakai Yoshitaka , Kusumoto Kiyonori , Itokawa Yoshio , Inatomi Osamu , Bamba Shigeki , Mizumoto Yoshinori , Tanaka Kiyohito
Published: December 2021

Background and Aim

International consensus on the definition and classification of post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) has been reached. However, the diagnosis and severity of PEP are often assessed according to the diagnostic criteria and classification for acute pancreatitis (AP). This study determined the incidence, severity, and risk factors of PEP diagnosed according to the diagnostic criteria and classification for AP in a large cohort.

Methods

This prospective, multicenter, observational cohort study conducted at five high‐volume centers included 1932 patients who underwent ERCP‐related procedures. The incidence, severity, and risk factors for PEP were evaluated.

Results

PEP occurred in 142 patients (7.3%); it was mild in 117 patients (6.0%) and severe in 25 patients (1.3%). According to the Cotton criteria, PEP occurred in 87 patients (4.5%); it was mild in 54 patients (2.8%), moderate in 20 patients (1.0%), and severe in 13 patients (0.7%). In the multivariate analysis, female sex (odds ratio [OR] 2.239; 95% confidence interval [CI] 1.546–3.243), naïve papilla (OR 3.047; 95% CI 1.803–5.150), surgically‐altered gastrointestinal anatomy (OR 2.538; 95% CI 1.342–4.802), procedure time after reaching the papilla (OR 1.009; 95% CI 1.001–1.017), pancreatic duct injection (OR 2.396; 95% CI 1.565–3.669), and intraductal ultrasonography (OR 1.641; 95% CI 1.024–2.629) were independent risk factors.

Conclusion

According to the diagnostic criteria and classification for AP, the incidence of PEP was higher than that according to the Cotton criteria and the severity of PEP tended to be severe.
Flexible circuits in the d‐dimensional rigidity matroid
Authors: Grasegger Georg , Guler Hakan , Jackson Bill , Nixon Anthony
Published: December 2021

A bar‐joint framework in is rigid if the only edge‐length preserving continuous motions of the vertices arise from isometries of . It is known that, when is generic, its rigidity depends only on the underlying graph , and is determined by the rank of the edge set of in the generic ‐dimensional rigidity matroid . Complete combinatorial descriptions of the rank function of this matroid are known when , and imply that all circuits in are generically rigid in when . Determining the rank function of is a long standing open problem when , and the existence of nonrigid circuits in for is a major contributing factor to why this problem is so difficult. We begin a study of nonrigid circuits by characterising the nonrigid circuits in which have at most vertices.
Iron, neuro‐bioavailability and depression
Authors: Berthou Christian , Iliou Jean Paul , Barba Denis
Published: December 2021

Medical management of iron deficiency (ID) requires to consider its consequences in biochemical and physiological plural functions, beyond heme/hemoglobin disrupted synthesis. Fatigue, muscle weakness, reduced exercise capacity, changes in thymia and modified emotional behaviors are the commonest symptoms integrated in the history of ID, dependent or not of the hemoglobin concentration. The relationship between depression and absolute ID (AID) is a condition which is often unrecognized. Neuro‐bioavailability and brain capture of blood iron are necessary for an appropriate synthesis of neurotransmitters (serotonin, dopamine, noradrenaline). These neurotransmitters, involved in emotional behaviors, depend on neuron aromatic hydoxylases functioning with iron as essential cofactor. Noradrenaline also has impact on neuroplasticity via brain‐derived neurotrophic factor (BDNF), which is key for prefrontal and hippocampus neurons playing a role in depression. Establishing the formal relationship between depression and AID remains difficult. Intracerebral reduced iron is still hard to quantify by neuroimaging and single‐photon emission computed tomography (SPECT) now tends to explore the neurotransmission pathways. AID has to be looked for and identified in the context of depression, major episode or resistant to conventional treatment such as serotonin reuptake inhibitor, and even in the absence of anemia, microcytosis or hypochromia (non‐anemic ID). Confronted to brain imaging, blood iron status evaluation is indicated, especially in depressed, treatment‐resistant, iron‐deficient young women. In patients suffering from depression, increase in the prevalence of AID should be considered, in order to deliver a suitable treatment, considering both anti‐depressive program and iron supplementation if AID.
Design, synthesis, and insecticidal evaluation of novel anthranilic diamides of N‐pyridylpyrazole derivatives containing 3‐thioethers
Authors: Sun Pengwei , Zhang Ze , Li Linshan , Wang Xinyao , Xiong Lixia , Yang Na , Li Yuxin , Li Zhengming
Published: December 2021

Thioether and its derivatives are important active pharmacophores, widely adopted in the molecular design of agrochemicals. The introduction of thioether into drug intermediate is important to improve the liposolubility, hydrophobicity, and bioactivity of molecules. For development of novel insecticides targeting at ryanodine receptor (RyR), a series of anthranilic diamides of N‐pyridylpyrazole derivatives containing 3‐thioether were designed and synthesized. The structures of these compounds were verified using 1H NMR, 13C NMR, and HRMS. Their insecticidal activities against Mythimna separata (M. separata, oriental armyworms) and Plutella xylostella (P. xylostella, diamondback moths) were evaluated and the preliminary structure–activity relationship (SAR) was discussed, among which 9f, 9g exhibited favorable insecticidal activities against M. separata at 5 mg/L (9f, 50%; 9g, 40%). In addition, insecticidal activity of the intermediate 8 indicated that bromomethyl group at 3‐position of pyrazole moiety has an important impact for retaining insecticidal activity. Calcium imaging experiment and molecular docking were carried out to elaborate insecticidal mechanism from the perspective of experiment and molecular simulation, respectively.
Lung Ultrasound in COVID‐19 and Post‐COVID‐19 Patients, an Evidence‐Based Approach
Authors: Demi Libertario , Mento Federico , Di Sabatino Antonio , Fiengo Anna , Sabatini Umberto , Macioce Veronica Narvena , Robol Marco , Tursi Francesco , Sofia Carmelo , Di Cienzo Chiara , Smargiassi Andrea , Inchingolo Riccardo , Perrone Tiziano
Published: December 2021

Objectives

Worldwide, lung ultrasound (LUS) was utilized to assess coronavirus disease 2019 (COVID‐19) patients. Often, imaging protocols were however defined arbitrarily and not following an evidence‐based approach. Moreover, extensive studies on LUS in post‐COVID‐19 patients are currently lacking. This study analyses the impact of different LUS imaging protocols on the evaluation of COVID‐19 and post‐COVID‐19 LUS data.

Methods

LUS data from 220 patients were collected, 100 COVID‐19 positive and 120 post‐COVID‐19. A validated and standardized imaging protocol based on 14 scanning areas and a 4‐level scoring system was implemented. We utilized this dataset to compare the capability of 5 imaging protocols, respectively based on 4, 8, 10, 12, and 14 scanning areas, to intercept the most important LUS findings. This to evaluate the optimal trade‐off between a time‐efficient imaging protocol and an accurate LUS examination. We also performed a longitudinal study, aimed at investigating how to eventually simplify the protocol during follow‐up. Additionally, we present results on the agreement between AI models and LUS experts with respect to LUS data evaluation.

Results

A 12‐areas protocol emerges as the optimal trade‐off, for both COVID‐19 and post‐COVID‐19 patients. For what concerns follow‐up studies, it appears not to be possible to reduce the number of scanning areas. Finally, COVID‐19 and post‐COVID‐19 LUS data seem to show differences capable to confuse AI models that were not trained on post‐COVID‐19 data, supporting the hypothesis of the existence of LUS patterns specific to post‐COVID‐19 patients.

Conclusions

A 12‐areas acquisition protocol is recommended for both COVID‐19 and post‐COVID‐19 patients, also during follow‐up.
Academic journals' usernames and the threat of fraudulent accounts on social media
Authors: Coates Adam
Published: December 2021

The internet has brought both benefits and risks for academia. Predatory publishing and conferences are well‐known, and less common academic cybercrime has also been identified, such as fraudulent conferences and journal hijacking. This study aimed to explore one further possible method for deceiving academics, namely, fraudulent accounts on social media. The study focused on two easily exploitable gaps in journals' social media engagement: whether journals have accounts on the most common social media platforms and whether journals use the same username across all their accounts. Evidence of fraudulent social media accounts was also sought. Drawing from a sample of 50 journals, the results indicate that many journals do not use social media, journals often use multiple usernames and fewer than half the accounts were officially verified. Some apparently fraudulent activity was found, but this was notably limited in scope and appeared to be politically rather than economically oriented. Further potential for deception was evident in accounts unaffiliated with a journal but registered with the journal's usernames and in the opportunity to create new social media accounts with journals' usernames. Journals are recommended to recognize this threat and some possible countermeasures are suggested.
Synthesis and Incorporation of Quaternary Ammonium Silane Antimicrobial into Self‐Crosslinked Type I Collagen Scaffold: A Hybrid Formulation for 3D Printing
Authors: Bapat Ranjeet Ajit , Muthusamy Senthil Kumar , Sidhu Preena , Mak Kit‐Kay , Parolia Abhishek , Pichika Mallikarjuna Rao , Seow Liang Lin , Tong Cao , Daood Umer
Published: December 2021

Novel 3D‐biomaterial scaffold is constructed having a combination of a new quaternary ammonium silane (k21) antimicrobial impregnated in 3D collagen printed scaffolds cross linked with Riboflavin in presence of d‐alpha‐tocopheryl poly(ethyleneglycol)‐1000‐succinate. Groups of “0.1% and 0.2% k21”, and “0.1% and 0.2% Chlorhexidine (CHX)” are prepared. k21/CHX with neutralized collagen is printed with BioX. Riboflavin is photo‐activated and examined using epifluorescence for Aggregatibacter actinomycetemcomitans (7‐days). Collagen is examined using TEM and measured for porosity, and shape‐fitting. Raman and tandem mass/solid‐state are performed with molecular‐docking and circular‐dichroism. X‐ray diffractions, rheological tests, contact angle, and ninhydrin assay are conducted. k21 samples demonstrated collagen aggregates while 0.1% CHX and 0.2% CHX showed irregularities. Porosity of control and “0.1% and 0.2% k21” scaffolds show no differences. Low contact angle, improved elastic‐modulus, rigidity, and smaller strain in k21 groups are seen. Bacteria are reduced and strong organic intensities are seen in k21 scaffolds. Simulation shows hydrophobicity/electrostatic interaction. Crosslinking is observed in 0.2% CHX/79% and 0.2% k21/80%. Circular dichroism for k21 are suggestive of triple helix. XRD patterns appear at d = 5.97, 3.03, 2.78, 2.1, and 2.90 A°. 3D‐printing of collagen impregnated with quaternary ammonium silane produces a promising scaffold with antimicrobial potency and structural stability.
Pitting behavior of the AA6061 alloy and Al5N in a diluted chloride solution
Authors: Linardi Evelina , Lanzani Liliana
Published: December 2021

The effect of aeration on the pitting potential (Ep) of the AA6061 alloy and high‐purity aluminum (Al5N) is studied in diluted chloride solutions. The Ep values are determined by a potentiodynamic scan in aerated and de‐aerated solutions of 10−3 M NaCl and 10−3 M NaCl + 0.05 M KH2PO4/K2HPO4 buffer. Applying the hypothesis testing procedure, it is concluded that the presence of oxygen in a 10−3 M NaCl solution decreases the Ep for AA6061 by 100 mV and does not affect the Ep for Al5N. This decrease is related to the alloy dissolution around the iron‐rich particles and is analyzed in terms of the model of localized acidification.
Collision energies: Optimization strategies for bottom‐up proteomics
Authors: Révész Ágnes , Hevér Helga , Steckel Arnold , Schlosser Gitta , Szabó Dániel , Vékey Károly , Drahos László
Published: December 2021

Mass‐spectrometry coupled to liquid chromatography is an indispensable tool in the field of proteomics. In the last decades, more and more complex and diverse biochemical and biomedical questions have arisen. Problems to be solved involve protein identification, quantitative analysis, screening of low abundance modifications, handling matrix effect, and concentrations differing by orders of magnitude. This led the development of more tailored protocols and problem centered proteomics workflows, including advanced choice of experimental parameters. In the most widespread bottom‐up approach, the choice of collision energy in tandem mass spectrometric experiments has outstanding role. This review presents the collision energy optimization strategies in the field of proteomics which can help fully exploit the potential of MS based proteomics techniques. A systematic collection of use case studies is then presented to serve as a starting point for related further scientific work. Finally, this article discusses the issue of comparing results from different studies or obtained on different instruments, and it gives some hints on methodology transfer between laboratories based on measurement of reference species.
Genetic algorithm‐based optimization of pulse sequences
Authors: Somai Vencel , Kreis Felix , Gaunt Adam , Tsyben Anastasia , Chia Ming Li , Hesse Friederike , Wright Alan J. , Brindle Kevin M.
Published: December 2021

Purpose

The performance of pulse sequences in vivo can be limited by fast relaxation rates, magnetic field inhomogeneity, and nonuniform spin excitation. We describe here a method for pulse sequence optimization that uses a stochastic numerical solver that in principle is capable of finding a global optimum. The method provides a simple framework for incorporating any constraint and implementing arbitrarily complex cost functions. Efficient methods for simulating spin dynamics and incorporating frequency selectivity are also described.

Methods

Optimized pulse sequences for polarization transfer between protons and X‐nuclei and excitation pulses that eliminate J‐coupling modulation were evaluated experimentally using a surface coil on phantoms, and also the detection of hyperpolarized [2‐13C]lactate in vivo in the case of J‐coupling modulation‐free excitation.

Results

The optimized polarization transfer pulses improved the SNR by ~50% with a more than twofold reduction in the B1 field, and J‐coupling modulation‐free excitation was achieved with a more than threefold reduction in pulse length.

Conclusion

This process could be used to optimize any pulse when there is a need to improve the uniformity and frequency selectivity of excitation as well as to design new pulses to steer the spin system to any desired achievable state.
On the compact difference scheme for the two‐dimensional coupled nonlinear Schrödinger equations
Authors: Rahmeni Mohamed , Omrani Khaled
Published: December 2021

A high‐order finite difference method for the two‐dimensional coupled nonlinear Schrödinger equations is considered. The proposed scheme is proved to preserve the total mass and energy in a discrete sense and the solvability of the scheme is shown by using a fixed point theorem. By converting the scheme in the point‐wise form into a matrix–vector form, we use the standard energy method to establish the optimal error estimate of the proposed scheme in the discrete L2‐norm. The convergence order is proved to be of a fourth‐order in space and a second‐order in time, respectively. Finally, some numerical examples are given in order to confirm our theoretical results for the numerical method. The numerical results are compared with exact solutions and other existing method. The comparison between our numerical results and those of Sun and Wangreveals that our method improves the accuracy of space and time directions.
“Giving the gift of life twice”: Understanding the lived experiences of parent donors and nondonors in pediatric haploidentical hematopoietic cell transplantation
Authors: Schaefer Megan R. , Aguilera Vanessa , Parris Kendra , Long Alanna , Triplett Brandon , Phipps Sean
Published: December 2021

Background

The use of parental donors in pediatric haploidentical hematopoietic cell transplantation is increasing, but research on the psychosocial impact of parental donation is currently limited.

Objectives

As part of a larger study, we conducted a retrospective, qualitative analysis to explore parental perceptions of the donation process and the impact of being a donor (or nondonor) on parents’ adjustment and coping with their child's transplant experience.

Methods

Parents/caregivers of children who underwent transplantation with a parental donor or a matched unrelated donor (N = 136) participated in interviews and completed an open‐ended questionnaire.

Results

Six themes were identified in the data: level of understanding and satisfaction; perception of choice; preparation for donation; perceptions of donation and infusion; benefit finding; and psychological impact of transplantation. Most parents were satisfied with the information they received and reported a good understanding of transplantation and donation procedures. Parents were divided on perspectives of choice, but their responses reflect that the necessity of saving their child's life does not allow for choice. They described considerable effort to prepare for transplantation, physically, emotionally, and logistically. Parents acknowledged the psychological impact while identifying positive outcomes that resulted from their child's transplant journey.

Conclusions

Results highlight the unique experiences of parental donors and nondonors from the anticipation phase to the completion of their child's transplant. Additionally, findings inform supportive care guidance by highlighting the need to assess parental donors’ emotional functioning, provide support post donation, and conduct bereavement follow‐up.
Severe fetal ventriculomegaly: Fetal morbidity and mortality, caesarean delivery rates and obstetrical challenges in a large prospective cohort
Authors: Start Alex O. , Ryan Gillian A. , Cathcart Barbara , Hughes Heather , Higgins Shane , Corcoran Siobhan , Walsh Jennifer , Carroll Stephen , Mahony Rhona , Crimmins Darach , Caird John , Colleran Gabrielle , McParland Peter , McAuliffe Fionnuala M.
Published: December 2021

Introduction

Severe fetal ventriculomegaly (VM) is defined as an enlargement of the atria of the lateral cerebral ventricles (Vp) of greater than 15 mm. While it is well established that it confers significant risk of morbidity and mortality to the neonate, there is limited information pertaining to the caesarean delivery rates and the obstetric management of these complex cases. The aim of this study was twofold: firstly, to determine survival rates in fetuses with severe VM, and secondly to determine the caesarean delivery rates in continuing pregnancies. We explore the obstetric challenges associated with these difficult cases.

Methods

This was a prospective observational study of patients with antenatal severe VM, attending the Department of Fetal Medicine, National Maternity Hospital, Dublin, Ireland, from 1st January 2011 to 31st July 2020. Data were obtained from the hospital database and those with severe VM (Vp > 15 mm) were identified. The rates of chromosomal abnormalities, the survival rates and the caesarean delivery (CD) rates for the overall group were then determined. The data were then further sub‐divided into two groups: 1. Vp < 20 mm and 2. Vp > 20 mm, and the results compared. Statistical analysis was performed using the Chi‐Square test.

Results

A total of N = 95 pregnancies with severe VM were included for analysis, of which additional structural abnormalities on ultrasound were apparent in 67/95 (70.5%) and 28/95 (29.5%) had isolated severe VM. Chromosomal abnormalities were diagnosed in 15/95 (15.8%) of cases, with (2/28) 7.1% in the isolated SVM group versus (13/67) 19.4% in the non‐isolated SVM group. The overall survival rate (excluding TOP) was 53/74 (71.6%), with 20/23 (86.9%) in the isolated SVM group. The overall CD rate was 47/72 (65.3%), which was significantly higher than the CD for the hospital during the same time period of 25.4% (P < 0.01).

The data were subdivided into Vp < 20 and Vp > 20 and those with a Vp > 20 had higher rates of additional intracranial findings on ultrasound (Vp < 20 13/41 (31.7%) versus Vp > 20 32/54 (59.3%) (P < 0.05)) and macrocrania (Vp < 20 14/41 (34.1%) versus Vp > 20 35/54 (64.8%) (P < 0.05)). No significant difference was observed in the overall survival or CD rates between the two groups.

Conclusion

In conclusion this study reports significant fetal morbidity and mortality with severe VM with high CD rates observed in this cohort. Significant challenges exist in relation to the obstetric management and counseling of parents regarding an often uncertain neonatal prognosis. In continuing pregnancies with significant macrocrania delivery plans should be individualized to improve neonatal outcomes where possible and minimize harm to the mother.
High‐risk opioid analgesic dispensing to adolescents 12–18 years old in South Carolina: 2010–2017
Authors: Basco William T. , McCauley Jenna L. , Zhang Jingwen , Marsden Justin E. , Simpson Kit N. , Heidari Khosrow , Mauldin Patrick D. , Ball Sarah J.
Published: December 2021

Purpose

To evaluate “high‐risk” opioid dispensing to adolescents, including daily morphine milligram equivalents (MME) above recommended amounts, the percentage of extended‐release opioid prescriptions dispensed to opioid‐naïve adolescents, and concurrent use of opioids and benzodiazepines, and to evaluate changes in those rates over time.

Methods

Retrospective cohort study of one state's prescription drug monitoring program data (2010–2017), evaluating adolescents 12–18 years old dispensed opioid analgesic prescriptions. Outcomes of interest were the quarterly frequencies of the high‐risk measures. We utilized generalized linear regression to determine whether the rate of the outcomes changed over time.

Results

The quarterly percentage of adolescents ages 12–18 years old dispensed an opioid who received ≥90 daily MME declined from 4.1% in the first quarter (Q1) of 2010 to 3.4% in the final quarter (Q4) of 2017 (p < 0.0001). The frequency of adolescents dispensed ≥50 daily MME changed little over time. In 2010, the percentage of adolescents receiving an extended‐release opioid who were opioid naïve was 60.7%, declining to 50.6% by Q4 of 2017 (p > 0.10 overall change 2010–2017). The percentage of adolescent opioid days overlapping with benzodiazepine days was 1.6% in Q1 of 2010, declining to 1.1% by Q4 of 2017 (p < 0.001).

Conclusions

Among persons 12–18 years old dispensed an opioid analgesic, receipt of ≥90 daily MME declined during the years 2010–2017, as did the percentage of adolescent opioid days that overlapped with benzodiazepines. More than half of the individuals who received extended‐release opioid analgesics were identified as opioid naïve and, counter to guidelines, received products intended for opioid‐tolerant individuals.
Anticholinergic medication burden and cognitive function in participants of the ASPREE study
Authors: Broder Jonathan C. , Ryan Joanne , Shah Raj C. , Lockery Jessica E. , Orchard Suzanne G. , Gilmartin‐Thomas Julia F.‐M. , Fravel Michelle A. , Owen Alice J. , Woods Robyn L. , Wolfe Rory , Storey Elsdon , Murray Anne M. , Ernst Michael E.
Published: December 2021

Study Objective

What is the association between anticholinergic burden and specific domains of cognitive function in older adults who are initially without major cognitive impairment?

Design

Post‐hoc analysis of longitudinal observational data from the ASPirin in Reducing Events in the Elderly (ASPREE) study.

Patients

19,114 participants from Australia and the United States aged 70 years and older (65 years and older for US minorities) were recruited and followed for a median of 4.7 years. At enrollment, participants were free of known cardiovascular disease, major physical disability, or dementia.

Measurements

Cognitive assessments administered at baseline and biennially at follow‐up visits included the Modified Mini‐Mental State examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT‐R) delayed recall, Controlled Oral Word Association Test (COWAT), and Symbol Digit Modalities Test (SDMT). Anticholinergic burden was calculated at baseline using the Anticholinergic Cognitive Burden (ACB) scale and grouped as scores of 0 (no burden), 1‐2 (low to moderate), or 3+ (high).

Main Results

Linear mixed effects models were used to assess the relationship between ACB score and cognition over time. After adjusting for sex, age, education, minority status, smoking status, hypertension, diabetes, depression, chronic kidney disease, country, and frailty, participants with a high ACB score had worse performance over time for 3MS (Adjusted [Adj] B=‐0.092, P=0.034), HVLT‐R delayed recall (Adj B=‐0.104, P<0.001), COWAT (Adj B=‐0.151, P<0.001), and SDMT (Adj B=‐0.129, P=0.026), than participants with an ACB score of 0. A low to moderate ACB score was also associated with worse performance over time for HVLT‐R delayed recall (Adj B=‐0.037, P=0.007) and COWAT (Adj B=‐0.065, P=0.003), compared to those with no ACB.

Conclusions

Anticholinergic burden predicts worse cognitive function over time in initially dementia‐free older adults, particularly for executive function (COWAT) and episodic memory (HVLT‐R).
Impact of elexacaftor/tezacaftor/ivacaftor on vitamin D absorption in cystic fibrosis patients
Authors: Wright Brittany A. , Ketchen Natalie K. , Rasmussen Leah N. , Bartels Alyssa R. , Singh Sachinkumar B.
Published: December 2021

Background

Cystic fibrosis (CF) is a multisystem disorder that results in the buildup of mucus in various organs. Ninety percent of CF patients are classified as pancreatic insufficient, leading to malabsorption of nutrients and fat‐soluble vitamins without the assistance of exogenous pancreatic enzymes. This study was designed to determine if serum 25‐hydroxyvitamin D concentrations were impacted by initiation of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA).

Methods

Serum 25‐hydroxyvitamin D concentrations were measured before and 1 year post‐ELX/TEZ/IVA initiation. A Wilcoxon signed‐rank test was used to compare values.

Results

Seventy‐six patients were included in the final analysis. The average age of our population was 25.8 years (SD = 13.2 years) with a majority being male, homozygous F508del, pancreatic insufficient, and not modulator‐naive. The median increase of serum vitamin D concentration after initiating ELX/TEZ/IVA was 5 ng/ml (interquartile range = −4, 13; p = .0035).

Conclusions

We suggest that ELX/TEZ/IVA may improve fat‐soluble vitamin absorption, specifically serum 25‐hydroxyvitamin D. These results may lead to adjustments in vitamin supplementation in patients receiving cystic fibrosis transmembrane conductance regulator modulator therapy.
Deformations of cyclodextrins and their influence to form inclusion compounds
Authors: Bautista‐Renedo Joanatan‐Michael , Hernández‐Esparza Raymundo , Cuevas‐Yañez Erick , Reyes‐Pérez Horacio , Vargas Rubicelia , Garza Jorge , González‐Rivas Nelly
Published: December 2021

Deformations of the three most common cyclodextrins (,, and) were induced to form inclusion compounds with sertraline and abacavir. The deformations were obtained from classical molecular dynamics (CMD) using as starting point X‐ray structures. The molecular dynamics were performed in two ways, over the cyclodextrins with and without the presence of a guest. Two characteristic rings within these cyclodextrins were used to measure the distortions observed along with the molecular dynamics. A docking approach was used to build inclusion compounds over the structures obtained from CMD without the presence of sertraline or abacavir. Thus, we compared structures of inclusion compounds obtained from deformations induced by the presence of a guest or with intrinsic deformations exhibited by each cyclodextrin. After this step, each structure was optimized by the PBE0‐D3/6‐31G(d,p) method, and the electron density delivered by this method was used to perform the quantum theory of atoms in molecules approach to analyze intermolecular contacts between sertraline, or abacavir, and three cyclodextrins. From this procedure, we found that inclusion compounds obtained from X‐ray structures present the highest energies over the potential energy surface. Thus, for getting low‐lying energy structures of inclusion compounds, deformations on cyclodextrins are necessary.
Is SARS‐CoV‐2 viral clearance in nasopharyngeal swabs an appropriate surrogate marker for clinical efficacy of neutralising antibody‐based therapeutics?
Authors: Focosi Daniele , Franchini Massimo , Pirofski Liise‐anne , Maggi Fabrizio , Casadevall Arturo
Published: December 2021

Viral clearance is likely the best way to assess the efficacy of antibody‐based therapies. Although antibodies can mediate a variety of effects that include modulation of inflammation, the demonstration of viral clearance provides an accessible and measurable parameter that can be used to evaluate efficacy and determine dosing. Therefore, it is important to ascertain the ability of monoclonal antibodies and convalescent plasma to effect viral clearance. For COVID‐19, which is caused by the respiratory virus SARS‐CoV‐2, the most common assay to assess viral clearance is via a nasopharyngeal swab (NPS). However, assessment of antibody efficacy by sampling this site may be misleading because it may not be as accessible to serum antibodies as respiratory secretions or circulating blood. Adding to the complexity of assessing the efficacy of administered antibody, particularly in randomised controlled trials (RCTs) that enroled patients at different times after the onset of COVID‐19 symptoms, viral clearance may also be mediated by endogenous antibody. In this article we critically review available data on viral clearance in RCTs, matched control studies, case series and case reports of antibody therapies in an attempt to identify variables that contribute to antibody efficacy and suggest optimal strategies for future studies.
Interpretation of TOF‐SIMS data based on information entropy of spectra
Authors: Aoyagi Satoka , Mizomichi Keisuke , Kamochi Keisuke , Miisho Ako
Published: December 2021

Time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS), when used for the analysis of complex material samples, typically provides data that are complicated and challenging to understand. Therefore, additional data analysis techniques, such as multivariate analysis, are often required to facilitate the interpretation of TOF‐SIMS data. In this study, a new method based on the information entropy (Shannon entropy) is proposed as an indicator of the outline characteristics of an unknown sample, such as changes in the material within the sample and mixing conditions. The Shannon entropy values are calculated using the relative intensity of every secondary ion normalized to the total ion count and reflect the diversity of secondary ions in the spectrum. Mixed samples containing two organic electroluminescence materials of different ratios, multilayers of Irganox 1010, and other organic materials were employed to evaluate the utility of Shannon entropy in the analysis of TOF‐SIMS data. The findings demonstrate that the Shannon entropy of a spectrum indicates differences in materials and changes in the conditions of a material in a sample without the need for peak identification or the knowledge of specific peaks corresponding to the materials in the sample.
Cobalt Catalysts for [2+2+2] Cycloaddition Reactions: Isolated Precatalysts and in situ Generated Catalysts
Authors: Gläsel Tim , Baumann Benedikt N. , Hapke Marko
Published: December 2021

[2+2+2] Cycloaddition reactions belong to the not even large class of reactions, which can be catalyzed or mediated by a significant number of different transition metals. Cobalt complexes belong to the catalysts that paved the way for the extensive use and profound mechanistic knowledge on this particular transformation. Beside the established role, cyclopentadienyl (Cp) cobalt complexes inherit in synthetic applications of the cyclotrimerization reaction, modification of the precatalysts opened up novel reactivities and versatility for such catalytic initiators. At the same time the development of in situ generated cobalt catalysts allowed the conversion of novel substrates as well as novel reaction modes to be realized. In this personal account recent developments will be presented and the possibilities of catalysts containing cobalt atoms in different oxidation states be discussed.