bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging of organ iron before and after correction of iron deficiency in patients with heart failure
Authors: Gertler Christoph , Jauert Nadja , Freyhardt Patrick , Valentova Miroslava , Aland Sven Christopher , Walter‐Rittel Thula Cannon , Unterberg‐Buchwald Christina , Placzek Marius , Ding‐Reinelt Virginia , Bekfani Tarek , Doehner Wolfram , Hasenfuß Gerd , Hamm Bernd , Sandek Anja
Published: March 2023

Aims

Intravenous iron therapy (IVIT) is known to improve functional status in chronic heart failure (CHF) patients. The exact mechanism is not completely understood. We correlated magnetic resonance imaging (MRI) patterns of T2* iron signal in various organs to systemic iron and exercise capacity (EC) in CHF before and after IVIT.

Methods and results

We prospectively analysed 24 patients with systolic CHF for T2* MRI pattern of the left ventricle (LV), small and large intestines, spleen, liver, skeletal muscle, and brain for iron. In 12 patients with iron deficiency (ID), we restored iron deficit by IVIT using ferric carboxymaltose. The effects after 3 months were analysed by spiroergometry and MRI. Patients with vs. without ID showed lower blood ferritin, haemoglobin (76 ± 63 vs. 196 ± 82 μg/L and 12.3 ± 1.1 vs. 14.2 ± 1.1 g/dL, all P < 0.002), and in trend a lower transferrin saturation (TSAT) (19.1 [13.1; 28.2] vs. 25.1 [21.3; 29.1] %, P = 0.05). Spleen and liver iron was lower as expressed by higher T2* value (71.8 [66.4; 93.1] vs. 36.9 [32.9; 51.7] ms, P < 0.002 and 33.5 ± 5.9 vs. 28.8 ± 3.9 ms, and P < 0.03). There was a strong trend for a lower cardiac septal iron content in ID (40.6 [33.0; 57.3] vs. 33.7 [31.3; 40.2] ms, P = 0.07). After IVIT, ferritin, TSAT, and haemoglobin increased (54 [30; 104] vs. 235 [185; 339] μg/L, 19.1 [13.1; 28.2] vs. 25.0 [21.0; 33.7] %, 12.3 ± 1.1 vs. 13.3 ± 1.3 g/L, all P < 0.04). Peak VO2 improved (18.2 ± 4.2 vs. 20.9 ± 3.8 mL/min/kg−1, P = 0.05). Higher peak VO2 at anaerobic threshold was associated with higher blood ferritin, reflecting higher metabolic exercise capacity after therapy (r = 0.9, P = 0.0009). Increase in EC was associated with haemoglobin increase (r = 0.7, P = 0.034). LV iron increased by 25.4% (48.5 [36.2; 64.8] vs. 36.2 [32.9; 41.9] ms, P < 0.04). Spleen and liver iron increased by 46.4 and 18.2%, respectively (71.8 [66.4; 93.1] vs. 38.5 [22.4; 76.9] ms, P < 0.04 and 33.5 ± 5.9 vs. 27.4 ± 8.6 ms, P < 0.007). Iron in skeletal muscle, brain, intestine, and bone marrow remained unchanged (29.6 [28.6; 31.2] vs. 30.4 [29.7; 30.7] ms, P = 0.7, 81.0 ± 6.3 vs. 82.9 ± 9.9 ms, P = 0.6, 34.3 ± 21.4 vs. 25.3 ± 14.1 ms, P = 0.2, 9.4 [7.5; 21.8] vs. 10.3 [6.7; 15.7] ms, P = 0.5 and 9.8 ± 1.5 vs. 13.7 ± 8.9 ms, P = 0.1).

Conclusions

CHF patients with ID showed lower spleen, liver, and in trend lower cardiac septal iron. After IVIT, iron signal of the left ventricle as well as spleen and liver increased. Improvement in EC was associated with increase in haemoglobin after IVIT. In ID, liver, spleen, and brain but not heart iron were associated with markers of systemic ID.
Five hot spots for international student mobility in 2023
Authors: Dennis Marguerite J.
Published: March 2023

It would be premature and superficial to predict country‐​by‐country international student mobility trends for 2023 because the political, economic, and social disruptions throughout the world are too fluid and directly impact international student mobility. However, there is one country's higher education mobility trends worth exploring. And that country is India.
WISC‐IV intellectual profiles in Italian children with self‐limited epilepsy with centrotemporal spikes
Authors: Zanaboni Martina Paola , Pasca Ludovica , Bova Stefania Maria , Chiappedi Matteo Alessio , Filippini Melissa , Giordano Lucio , Grumi Serena , Micheletti Serena , Operto Francesca F. , Pruna Dario , Ragona Francesca , Raviglione Federico , Totaro Martina , Varesio Costanza , Vignoli Aglaia , De Giorgis Valentina ,   The EpilEpsyIt study group
Published: March 2023

Objective

This study aimed to describe the intellectual profile based on the Wechsler Intelligence Scale for Children 4th edition (WISC‐IV) in children with self‐limited epilepsy with centrotemporal spikes (SeLECTS), with an attempt to define possible predictive epilepsy‐related variables of cognitive performance.

Methods

The WISC‐IV was assessed in 161 children with SeLECTS and their cognitive profiles were compared to a matched sample of healthy control children.

Results

Children with SeLECTS performed within normal range across all indices, demonstrating particular strength based on the Perceptual Reasoning Index. Compared to healthy control children, we observed a significant difference in performance based on the Full Scale Intelligence Quotient, Verbal Comprehension Index and Processing Speed Index. Regarding epilepsy‐related variables, earlier onset of epilepsy, use of anti‐seizure medications, the presence of neurodevelopmental disorders, a higher frequency of seizures, and a longer treatment duration were associated with an overall lower level of performance.

Significance

Children with SeLECTS performed within the average range for cognitive assessment based on the WISC‐IV, demonstrating that children had normal levels of global intelligence. However, compared to healthy control children, children with SeLECTS showed a slightly lower level of performance. Reasoning skills represented the relative strengths in children with SeLECTS. Predictors of intellectual performance in patients with SeLECTS include epilepsy‐related variables and neurodevelopmental comorbidities.
Hydrogen supply chain: Current status and prospects
Authors: Monteiro Eliseu , Brito Paulo S. D.
Published: March 2023

In the current world energy scenario with rising prices and climate emergencies, the renewable energy sources are essential for reducing pollution levels triggered by carbon‐based fuels. Hydrogen rises in the world energy scenario as an important non‐carbon‐based energy able to replace fossil fuels. For this reason, the rapid development of hydrogen‐related technology has been seen in recent years. This review paper covers hydrogen energy systems from fossil fuel‐based hydrogen production, biomass and power from renewable energy sources, to hydrogen storage in compressed gases, liquefied and solid materials, and hydrogen‐based power generation technology. It represents a quiet complete set of references that may be effective in increasing the prospects of hydrogen as a fuel in the coming years. The main conclusions drawn are that natural gas and coal supply nearly all of the current hydrogen. The commercially available technologies for hydrogen production are steam methane reforming, partial oxidation, and alkaline electrolysis. The most economical methods for hydrogen production are partial oxidation, steam methane reforming, coal gasification, and biomass gasification. Metallic cylindrical reservoirs are the most promising alternative to underground storage of compressed hydrogen at large scales. Some metal compounds and composites can store a significant amount of hydrogen while maintaining reasonable adsorption and desorption kinetics. The transportation sector is likely to see widespread use of hydrogen in the future, helping to reduce pollution. Vehicles can be powered by fuel cells, which are much more efficient than internal combustion engines. There are still several obstacles in the way of widespread hydrogen utilization. The first one is that the cost of producing hydrogen from low‐carbon sources is elevated. As the cost of renewable energy declines and hydrogen production is scaled up, it is anticipated that the hydrogen production costs would decrease over the next years. Innovative technologies are expected to increase the interest on thermochemical hydrogen production to massively substitute electrochemical technologies since they are theoretically cost‐effective. More research is needed to fix concerns with some of the thermochemical cycles in order to rise its maturity. Increasing the chemical reaction conversion ratios, which can be resolved utilizing nonequilibrium reactions, is one of them. The transportation sector is likely to see extensive use of hydrogen in the future, helping to reduce carbon dioxide emissions. The power required by vehicles may be supplied by fuel cells, which are more efficient than internal combustion engines.
Effects of coenzyme Q10 supplementation on lipid profiles and liver enzymes of nonalcoholic fatty liver disease (NAFLD) patients: A systematic review and meta‐analysis of randomized controlled trials
Authors: Ardekani Ali , Tabrizi Reza , Maleki Elham , Bagheri Lankarani Kamran , Heydari Seyed Taghi , Moradinazar Mehdi , Akbari Maryam
Published: March 2023

As an antioxidant, coenzyme Q 10 (CoQ10) has been proposed as a possible treatment for non‐alcoholic fatty liver disease (NAFLD). In the present meta‐analysis, we aimed to determine the effects of CoQ10 supplementation on lipid profiles and liver enzymes of NAFLD patients. We searched PubMed, Web of Science, Scopus, and Cochrane Library on 21 April 2022 to retrieve randomized controlled trials on NAFLD patients in which CoQ10 was utilized as a treatment. Data were pooled using the random‐effects model and weighted mean difference (WMD) was considered as the summary effect size. The analysis of the six included studies indicated an overall non‐significant decrease in the lipid profiles (total cholesterol (TC), low‐density lipoprotein cholesterol (LDL), high‐density lipoprotein cholesterol (HDL), and triglyceride (TG)), and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and gamma‐glutamyltransferase (GGT)) of NAFLD patients who received CoQ10. Sensitivity analysis using “leave‐one out” method showed a significant reduction in AST, and GGT after excluding certain studies. Also, subgroup analyses showed significant difference based on CoQ10 dose for TC, AST, and GGT, and also a significant decrease in AST based on the duration of the intervention. No publication bias was found between the studies. Although an overall non‐significant decrease was observed in lipid profiles and liver enzymes of NAFLD patients, the results of sensitivity and subgroup analyses showed significant effects of CoQ10 in certain conditions. Further RCTs should be done in light of our findings.
An economic impact of incorrect referrals for MRI and CT scans: A retrospective analysis
Authors: Baiguissova Dinara , Laghi Andrea , Rakhimbekova Assel , Fakhradiyev Ildar , Mukhamejanova Aigerim , Battalova Galina , Tanabayeva Shynar , Zharmenov Samat , Saliev Timur , Kausova Galina
Published: March 2023

Background and Aims

Up to date, no research on the economic efficacy of diagnostic modalities, such as magnetic resonance imaging (MRI) and computerized tomography (CT), has been done in Central Asia. The aim of this study was to analyse the inappropriate appointments of MRI and CT scanning procedures in Kazakhstan.

Methods

We used the imaging diagnostic reports and medical records from 9725 planned outpatient CT and MRI exams performed in two major hospitals in Almaty. The study period was for the period 2014–2019. The independent experts‐radiologists evaluated the MRI and CT exams for validity using the ACR® compliance standards and RCR recommendations.

Results

The results showed that the combined costs of MRI and CT scans increased by $17.982 between 2014 ($22.537) and 2019 ($40.519), p = 0.002. The highest rate of MRI examinations was observed in 2019, with a rate of 6.9 per 10,000 people. It was determined that in 2019 the highest rate for men who undertook CT was equal to 12.4 per 10,000 people, while for women it was equivalent to 5.7 per 10,000 patients. The majority of non‐corresponding imaging examinations (n = 1304) were referred for MRI and CT scans by general practitioners. We detected the irrational referrals for head and neck radiological examinations in n = 178 (13.7%) cases, and the abdominal cavity checks in n = 249 (19.1%) cases (p = 0.001). The main portion of erroneously unreasonable referrals for examination of the abdominal organs was made by surgeons in n = 43 (3.3%) cases.

Conclusion

The findings indicated an increase in the number of referrals for unnecessary CT and MRI tests over the research period (2014–2019). It had a substantial impact on the rise in healthcare system expenses. The results demonstrate the need for the education of GPs and improving the approaches for diagnostics.
Higenamine Promotes Osteogenesis Via IQGAP1/SMAD4 Signaling Pathway and Prevents Age- and Estrogen-Dependent Bone Loss in Mice
Authors: Dong Hui , Liu Ronghan , Zou Ke , Jin Zhengxin , Kang Jianning , Zhang Ying , Zhang Xiaodi , Sun Zhengfang , Yu Guilian , Huang Nana , Bretches Morgan , Yang Shang-You , Ning Bin
Published: March 2023

Osteoporosis is a common bone disease caused by an imbalance of bone resorption and formation that results in a loss of total bone density. SMAD2/3 signal transduction is known to play a crucial role in osteogenic differentiation through transforming growth factor-beta (TGF-β). By screening a library of small-molecule compounds, the current study identifies higenamine (HG) as an active osteogenic agent that could be a therapeutic candidate for osteoporosis. In vitro data demonstrated that HG effectively induced expressions of osteogenic markers in mouse bone marrow stromal cell (BMSCs) and preosteoblastic cell cultures. Further, HG treatment resulted in enhanced bone formation and prevented accelerated bone loss on two animal models that mimic spontaneous senile osteoporosis and postmenopausal osteoporosis. IQ motif-containing GTPase-activating protein 1 (IQGAP1) was confirmed as a novel target of HG, where HG appears to bind to the Glu-1019 site of IQGAP1 to exert its osteogenic effects. Data subsequently suggested that HG promoted phosphorylation of SMAD2/3 and regulated the SMAD2/3 pathway by inhibiting SMAD4 ubiquitination. Overall, the findings highlight HG as a new small-molecule drug to promote bone formation through SMAD2/3 pathway in osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).

Abstract

Higenamine is elucidated to upregulate SMAD2/3 signaling through binding IQGAP1, which leads to the inhibition of SMAD4 ubiquitination and thereby promotion of the expression of key osteogenesis genes.
Brokerage, power and gender equity: How empowerment‐focused civil society organisations bolster women's influence in rural Indonesia
Authors: Diprose Rachael
Published: March 2023

This article explores how empowerment‐focused Civil Society Organisations (CSOs) traverse scales and perform brokerage functions in helping rural women from marginal groups to connect to and influence powerholders in Indonesia. It identifies three brokerage mechanisms activated by these CSOs: brokering marginal groups' power bases through strengthening organising structures and sources of knowledge/resources; brokering spaces for women's influence on powerholders; and brokering networks with other women and authoritative actors to build supporting coalitions. The article also illustrates that contexts shape how CSO interventions affect change: heavy, resource‐intensive ‘thick’ brokerage strategies were important in deeply patriarchal contexts, whereas ‘thin’ brokerage strategies had some effects in places already more conducive to improving gender equity.
Causal association of the brain structure with the susceptibility, hospitalization, and severity of COVID‐19: A large‐scale genetic correlation study
Authors: Fan Zhihua , Ruan Zhe , Liu Zhi , Guo Bin , Wang Chao , Fan Xuegong , Chen Lizhang , Zhao Shushan
Published: March 2023

Brain structure is related to its ability to resist external pathogens. Furthermore, there are several abnormal anatomical brain events and central system symptoms associated with COVID‐19. This study, which was conducted based on genetic variables, aimed to identify the causal association between brain structure and COVID‐19 phenotypes. We performed a two‐sample bidirectional Mendelian randomization analysis using genetic variables obtained from large genome‐wide association studies as instruments to identify the potential causal effects of various brain imaging‐derived phenotypes (BIDPs) traits on susceptibility, hospitalisation, and severity of COVID‐19. We explored the genetic correlations of 1325 BIDPs with the susceptibility, hospitalisation, and severity of COVID‐19 using Linkage Disequilibrium Score Regression. We observed a causal relationship between increased cortical thickness of the left inferior temporal area and an increased risk of increased COVID‐19 infection (p = 4.29 × 10‐4) and hospitalisation (p = 3.67 × 10‐3). Moreover, the larger total surface area of the whole brain was negatively correlated with the risk of hospitalisation for COVID‐19. Furthermore, there was a significant causal association between increased cerebrospinal fluid volume and decreased severity of COVID‐19 (p = 3.74 × 10‐3). In a conclusion, we provide new insights into the causal association between BIDPs and COVID‐19 phenotypes, which may help elucidate the aetiology of COVID‐19.
Coxsackievirus B: The important agent of hand, foot, and mouth disease
Authors: Liu Yuhan , Chen Junwei , Zhang Ming , Guo Wei , Feng Changzeng , Liu Jiansheng , Xu Lilan , Gao Na , Ma Shaohui
Published: March 2023

Hand, foot, and mouth disease (HFMD) is a common pediatric infectious illness caused by enteroviruses (EVs). EV‐A serotypes are the main pathogens associated with HFMD. In this study, 213 stool samples from 213 children with severe HFMD in Yunnan, China in 2013, 2015, and 2016 were further analyzed retrospectively for EV‐B infection. A total of 70.0% of the specimens tested positive for EV.20 EV serotypes were detected. The predominant serotype was enterovirus A71 (EV‐A71, 27.7%), followed by coxsackievirus B4 (CV‐B4, 16.4%), CV‐A16 (9.9%), CV‐B5 (6.6%), and Echovirus 9 (E‐9,4.7%). EV‐A and EV‐B accounted for 45.1% and 41.3%, respectively. Among the positive specimens, 28.6% were CV‐Bs. Co‐infection was present in 19.3% of these cases. In the study, CV‐B5 and the majority of CV‐B4 isolates belonged to genotypes VI and C3, respectively. This result indicates that EV‐B, especially CV‐Bs, might be the important agents associated with HFMD and this knowledge will contribute to the prevention and treatment of the disease.
Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis
Authors: Li Wei , Gao Zhi , Guan Qing‐Long
Published: March 2023

Tanshinone IIA (Tan IIA) has an important role in treatment of cardiovascular diseases, including atherosclerosis. The vascular smooth muscle cells (VSMCs) are a major part of the atherosclerotic plaque. However, the biological functions of Tan IIA in regulating VSMCs function remain mostly unclear. This research aimed at identifying the explicit molecular mechanism that Tan IIA regulates oxidized low‐density lipoprotein (ox‐LDL)‐mediated VSMC proliferation and migration. VSMCs challenged by ox‐LDL were adopted as cellular model of atherosclerosis, and suffered from Tan IIA treatment. After that, cells proliferation, apoptosis or migration were measured. The expression levels of microRNA (miR)‐137, transient receptor potential cation channel subfamily C member 3 (TRPC3) and proliferating cell nuclear antigen (PCNA) were measured. The targeting relationship between miR‐137 and TRPC3 was determined. It was found that Tan IIA blunted VSMC proliferation, PCNA expression and migration mediated by ox‐LDL. Tan IIA promoted miR‐137 level, and miR‐137 knockdown reversed the influences of Tan IIA on VSMC proliferation, PCNA expression and migration in the presence of ox‐LDL. TRPC3 was verified to be targeted by miR‐137. Moreover, TRPC3 silencing exacerbated the influences of Tan IIA on VSMC proliferation, apoptosis and migration, and it mitigated the inhibitive effects of miR‐137 knockdown on function of Tan IIA. We confirmed for the first time that Tan IIA constrained ox‐LDL‐stimulated VSMC proliferation and migration via regulating the miR‐137/TRPC3 axis, which provided a theoretical basis for the research and promotion of Tan IIA as a therapeutic drug.
B‐cell Lymphoma Presenting as Nasal Septal Perforation
Authors: Ghanem Anthony , Alam Elie , Aoun Jessica
Published: March 2023

Sinonasal lymphoma is a rare clinical entity. Three main subtypes exhibit different clinical patterns and treatment outcomes. We report the first case of a B‐cell lymphoma in a patient without any previous history of nasal surgery, trauma or drug use, who presented to our center with a nasal septal perforation. Laryngoscope, 133:2871–2873, 2023
Hypoglossal Nerve Stimulation as Treatment for Obstructive Apnea in a Patient with a Pharyngeal Flap
Authors: Scheffler Patrick , Eitan Dana , Drewek Rupali , Gnagi Sharon
Published: March 2023

Hypoglossal nerve stimulation can be a successful form of treatment for obstructive sleep apnea in patients with a pharyngeal flap. Although the Inspire device is geared at relieving obstructive sleep apnea due to tongue base obstruction, it can still be highly efficacious in improving AHI and OSA symptoms in the presence of nasopharyngeal narrowing from the pharyngeal flap. Laryngoscope, 133:2428–2429, 2023
Actinomyces: An Under Appreciated Cause of Postoperative Infection in Rhinoplasty
Authors: Eitan Dana N. , Grunebaum Lisa D. , Howard Brittany E.
Published: March 2023

Objective

To discuss a case series of Actinomyces infection post‐rhinoplasty and review the literature for correct diagnosis and management.

Study Design

Case series with chart review.

Methods

Three cases are presented of patients with a history of recurrent infectious symptoms post revision rhinoplasty later being diagnosed as Actinomyces.

Results

Three patients were identified having undergone revision rhinoplasty and later being diagnosed with Actinomyces infection. They initially presented with underwhelming physical exams, mild erythema, slight swelling, yet extreme pain. They also had periods of recurrent infection once antibiotics were stopped. Aerobic, anaerobic, fungal, and Actinomyces cultures were sent to pathology and returned positive for Actinomyces. Treatment typically involved a combination of prolonged antibiotics, incision and drainage, and/or surgical debridement.

Conclusions

Awareness of Actinomyces as a possible cause of infection post‐rhinoplasty is significant as this pathogen can lead to extensive tissue destruction and fistula formation which could be detrimental for a rhinoplasty. Duration of treatment is beyond typical lengths for other infections and a specific culture for Actinomyces is required to be sent as it isn't captured in standard aerobic/anaerobic cultures. Therefore, a high index of suspicion is required by physicians to ensure that patients are evaluated thoroughly. Laryngoscope, 133:2948–2950, 2023
Treatments for Age‐related Vocal Atrophy: A Systematic Review
Authors: Bhatt Neel K. , Garber David , Baertsch Hans , Beard Lynly , Giliberto J. P. , Meyer Tanya K. , Merati Albert L. , Sauder Cara
Published: March 2023

Objective

Age‐related vocal atrophy (ARVA) can dramatically affect voice, communication, and quality of life. The objectives of this systematic review were to (1) determine whether treatments for ARVA were superior to controls (2) compare the relative efficacy of procedural and behavioral treatments (3) review the various types of outcome measures, and (4) evaluate the quality of studies.

Review Methods

The literature was searched using strategies designed by a medical librarian (2/18/21, updated 3/9/22). Studies investigating treatments for bilateral vocal atrophy were included. Studies involving unilateral atrophy, presbyphonia (without endoscopic findings), or an absent comparator group were excluded. The Preferred Reporting Items for Systematic Reviews and Meta‐analyses checklist was used to guide this study.

Results

After applying the inclusion/exclusion criteria, 8 articles remained, including 4 randomized trials and 4 cohort studies, and a narrative synthesis was performed. Surgical and behavioral treatments for ARVA appeared to be superior to control groups, based on specific outcome measures. However, the superiority of these treatments over controls was not uniformly observed across multiple outcome measures. When comparing different treatments, superiority could not be established based on the quality and completeness of the studies included in the systematic review. Outcome measures also varied between individual studies. Finally, the risk of bias was analyzed and scored. Consistent point deductions among reviewed studies were noted.

Conclusions

When comparing treatments for ARVA. Surgery and voice therapy were both superior to control groups based on specific outcome measures from different domains. Superiority of one treatment could not be established.

Level of Evidence

N/A Laryngoscope, 133:2846–2855, 2023
Ultrabroadband Multichannel Vector Vortex Beams With Versatile Electrically Induced Functionality
Authors: Sun Peizhi , Liu Binghui , Wang Yifei , Yuan Conglong , Jia Shuzhen , Shen Dong , Zheng Zhi‐Gang
Published: March 2023

The emergence of vector vortex beams (VVBs) has opened new avenues for various applications in optics and photonics. However, owing to the formidable phase aberration ascribed to the chromatic dispersion, the generation of VVBs suffers from a limited working spectrum, thus rendering the massive integration level and functionality challenging. Here, this work proposes a creative paradigm to generate ultrabroadband multichannel VVBs, via programming the electric field vector through the twisted nematic liquid crystals configured by photopatterning. It is experimentally demonstrated the multichannel VVBs propagate along a group of diffraction orders among an unprecedented bandwidth over 1000 nm covering the visible and NIR band, and the working spectrum can be extended into the mid‐IR region even at 10 µm wavelength with a sufficient efficiency of more than 80%. Remarkably, distinct from the usual electrical switching on–off cycle, the multichannel VVBs can be optionally regulated in either a reversible or irreversible manner by conveniently adjusting the applied voltage, thus endowing the versatile functionality for smart control and confidential purposes. The combination of multichannel VVB generation, ultrabroad spectral range, versatile controllability, and simplicity renders the methodology quite promising in photonics, quantum science, and fundamental physics.
Atomistic MD Simulations of n‐Alkanes in a Phospholipid Bilayer: CHARMM36 versus Slipids
Authors: Wurl Anika , M. Ferreira Tiago
Published: March 2023

Linear alkanes (n‐alkanes) are chemically the most simple linear hydrophobic molecules in nature. Studying the incorporation of n‐alkanes into lipid membranes is therefore a good starting point toward understanding the behavior of hydrophobic molecules in lipid membranes and to assess how accurately molecular dynamics models describe such systems. Here, the miscibility and structure of different n‐alkanes—n‐decane (C10), n‐eicosane (C20), and n‐triacontane (C30)—in dipalmitoylphosphatidylcholine membranes are investigated using two of the most used force fields for lipid membrane molecular dynamics simulations (CHARMM36 and Slipids). The n‐alkanes are miscible in the membrane up to a critical volume fraction, ϕc, that depends on the force field interaction parameters used. ϕc is dependent on alkane chain length only for the model with more disordered chains (Slipids). Below ϕc, a comparison with 2H nuclear magnetic resonance (NMR) spectra indicates that a more realistic structure of the longer alkane molecules (C20 and C30) is obtained using the Slipids force field. On the other hand, for the shorter alkane (C10), Slipids simulations underestimate molecular order and CHARMM36 simulations enable a precise prediction of its experimental spectrum. The predicted 2H NMR spectra are highly sensitive to 1–4 electrostatic interactions, and suggest that a reduction of the partial charges of the longer alkanes and acyl chains in CHARMM36 results in a better performance. The results presented indicate that lipid membranes with incorporated alkanes are highly valuable systems for the validation of force fields designed to perform lipid membrane simulations.
Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease
Authors: Muñoz‐Delgado Laura , Labrador‐Espinosa Miguel Ángel , Macías‐García Daniel , Jesús Silvia , Benítez Zamora Belén , Fernández‐Rodríguez Paula , Adarmes‐Gómez Astrid D. , Reina Castillo María Isabel , Castro‐Labrador Sandra , Silva‐Rodríguez Jesús , Carrillo Fátima , García Solís David , Grothe Michel J. , Mir Pablo
Published: March 2023

Background

Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil‐to‐lymphocyte ratio (NLR) is a well‐established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [123I]FP‐CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density.

Objectives

To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD.

Methods

We assessed clinical features, the peripheral immune profile, and striatal [123I]FP‐CIT DAT binding levels of 211 patients with PD (primary‐cohort). Covariate‐controlled associations between the immune response and striatal DAT levels were assessed using linear regression analyses. For replication purposes, we also studied a separate cohort of 344 de novo patients with PD enrolled in the Parkinson's Progression Markers Initiative (PPMI‐cohort).

Results

A higher NLR was significantly associated with lower DAT levels in the caudate (primary‐cohort: β = −0.01, p < 0.001; PPMI‐cohort: β = −0.05, p = 0.05) and the putamen (primary‐cohort: β = −0.05, p = 0.02; PPMI‐cohort: β = −0.06, p = 0.02). Intriguingly, a lower lymphocyte count was significantly associated with lower DAT levels in both the caudate (primary‐cohort: β = +0.09, p < 0.05; PPMI‐cohort: β = +0.11, p = 0.02) and the putamen (primary‐cohort: β = +0.09, p < 0.05, PPMI‐cohort: β = +0.14, p = 0.01), but an association with the neutrophil count was not consistently observed (caudate; primary‐cohort: β = −0.05, p = 0.02; PPMI‐cohort: β = 0, p = 0.94; putamen; primary‐cohort: β = −0.04, p = 0.08; PPMI‐cohort: β = −0.01, p = 0.73).

Conclusions

Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Surface Molecularly Imprinted Cellulose‐Synthetic Hybrid Particles Prepared via ATRP for Enrichment of Flavonoids in Olive Leaf
Authors: Gomes Catarina P. , Dias Rolando C. S. , Costa Mário Rui P. F. N.
Published: March 2023

Surface molecularly imprinted cellulose‐synthetic hybrid particles are prepared via atom transfer radical polymerization (ATRP). The two‐step process involves the immobilization of α‐bromoisobutyryl bromide in the pristine microcrystalline cellulose, to generate ATRP macroinitiator particles, and then the creation of a crosslinked‐imprinted shell in the particles surface considering ATRP of 4‐vinylpyridine (4VP) and ethylene glycoldimethacrylate (EGDMA) with quercetin as imprinting template. Among the polymerization recipes tested, a system with ethanol as solvent preserves a final size of the hybrid particles suitable for application as adsorbent, while also incorporating the 4VP/EGDMA co‐monomers. Testing of imprinted/non‐imprinted particles for sorption/desorption of standard phenolic compounds shows the modification of the surface of the pristine cellulose and also the achievement of molecular imprinting (imprinting factor ≈2.6). Particles are used for the enrichment of flavonoids in olive leaf extracts and the special features of the developed molecularly imprinted adsorbents are again highlighted with this complex mixture of phenolic compounds. It is shown that production of fractions rich in luteolin‐7‐O‐glucoside, apigenin‐7‐O‐glucoside, or quercetin, among other flavonoids is possible (estimated enrichment factors up to 4). These results point up for the usefulness of natural‐synthetic materials with processes to get high‐added value compounds in the framework of circular bio‐economy.
B1 mapping using an EPI‐based double angle approach: A practical guide for correcting slice profile and B0 distortion effects
Authors: Nöth Ulrike , Shrestha Manoj , Deichmann Ralf
Published: March 2023

Purpose

Aim of this study was to develop a reliable B1 mapping method for brain imaging based on vendor MR sequences available on clinical scanners. Correction procedures for B0 distortions and slice profile imperfections are proposed, together with a phantom experiment for deriving the approximate time‐bandwidth‐product (TBP) of the excitation pulse, which is usually not known for vendor sequences.

Methods

The double angle method was used, acquiring two gradient echo echo‐planar imaging data sets with different excitation angles. A correction factor C (B1, TBP, B0) was derived from simulations for converting double angle method signal quotients into bias‐free B1 maps. In vitro and in vivo tests compare results with reference B1 maps based on an established in‐house sequence.

Results

The simulation shows that C has a negligible B1 dependence, allowing for a polynomial approximation of C (TBP, B0). Signal quotients measured in a phantom experiment with known TBP reconfirm the simulation results. In vitro and in vivo B1 maps based on the proposed method, assuming TBP = 5.8 as derived from a phantom experiment, match closely the reference B1 maps. Analysis without B0 correction shows marked deviations in areas of distorted B0, highlighting the importance of this correction.

Conclusion

Double angle method‐based B1 mapping was set up for vendor gradient echo‐echo‐planar imaging sequences, using a correction procedure for slice profile imperfections and B0 distortions. This will help to set up quantitative MRI studies on clinical scanners with release sequences, as the method does not require knowledge of the exact RF‐pulse profiles or the use of in‐house sequences.
Nonlinear stochastic dynamics of an array of coupled micromechanical oscillators
Authors: Katsidoniotaki Maria I. , Petromichelakis Ioannis , Kougioumtzoglou Ioannis A.
Published: March 2023

The stochastic response of a multi‐degree‐of‐freedom nonlinear dynamical system is determined based on the recently developed Wiener path integral (WPI) technique. The system can be construed as a representative model of electrostatically coupled arrays of micromechanical oscillators, and relates to an experiment performed by Buks and Roukes. Compared to alternative modeling and solution treatments in the literature, the paper exhibits the following novelties. First, typically adopted linear, or higher‐order polynomial, approximations of the nonlinear electrostatic forces are circumvented. Second, for the first time, stochastic modeling is employed by considering a random excitation component representing the effect of diverse noise sources on the system dynamics. Third, the resulting high‐dimensional, nonlinear system of coupled stochastic differential equations governing the dynamics of the micromechanical array is solved based on the WPI technique for determining the response joint probability density function. Comparisons with pertinent Monte Carlo simulation data demonstrate a quite high degree of accuracy and computational efficiency exhibited by the WPI technique. Further, it is shown that the proposed model can capture, at least in a qualitative manner, the salient aspects of the frequency domain response of the associated experimental setup.
Bioorthogonal chemical imaging of solid lipid nanoparticles with minimal labeling by stimulated Raman scattering microscopy
Authors: Lang Xiaoqi , Gao Xin , Wei Mian , Qian Naixin , Min Wei
Published: March 2023

Solid lipid nanoparticles (SLNs) are a state‐of‐the‐art lipid‐based pharmaceutical drug delivery system. Advantages of SLNs include high biocompatibility, low immunogenicity, superiority in drug encapsulation capacity, and improved colloidal stability. They became widely known in late 2020, as several COVID‐19 vaccines are built upon SLNs technology. Despite the increasing impact, the characterization methods of SLNs are currently very limited especially in biological environment, which hinders fundamental understanding of the delivery mechanism and contributes to relatively low success rate in clinical translations. Here, we present close‐to‐label‐free imaging of deuterated SLNs using the emerging stimulated Raman scattering (SRS) microscopy. The introduction of deuterium to lipid structure renders bioorthogonal chemical specificity. Notably, with this approach, we have achieved ultrahigh single‐particle sensitivity both in vitro and in vivo, even with particle counting ability. Our bioorthogonal chemical imaging modality by SRS microscopy can be generalized to visualize a wide spectrum of lipid‐based drug carriers with high spatiotemporal resolution, chemical specificity, and ultimate sensitivity. This work opens up ways to address critical questions in SLN drug delivery and could also facilitate innovations in lipid nanotechnology and clinical translations.

Key points

Direct imaging of lipid nanocarrier that is the basis of the COVID‐19 vaccines.

Novel single‐particle imaging technique applied to nanomedicine.

Frontier of nanomaterial, optical imaging, and molecular pharmacology.
The contribution of crowdfunding for philanthropy: A systematic review and framework of donation and reward crowdfunding
Authors: van Teunenbroek Claire , Dalla Chiesa Carolina , Hesse Laura
Published: March 2023

Which novelties do donation‐ and reward‐based crowdfunding bring to philanthropy? Scholars interested in crowdfunding contributed to developing empirical explanations on which features impact online giving. However, the focus on theory building is limited. We developed a theoretical framework by categorizing the empirical findings reported in 198 studies, which resulted in four crowdfunding features impacting giving: (1) project creator, (2) social information, (3) rewards, and (4) project description. We explain why these features impact giving by integrating them with insights from several fields of social sciences, deriving seven giving mechanisms. We conclude that with impacting donations via crowdfunding, three giving themes exist: being affected by (1) the perceived project's quality, (2) social connections and/or (3) tangible rewards. The categorization of mechanisms for giving allows initiators to extract best practice examples for increasing the probability of successful crowdfunding projects considering the giving mechanisms.
Regulating Zhibo in China: Exploring multiple levels of self‐regulation and stakeholder dynamics
Authors: Qiu Yuanbo , Dwyer Timothy
Published: March 2023

In recent years, user‐generated live streaming platforms have grown significantly in their popularity. However, the circulation of objectionable live streaming content and the unpredictability and high‐intensity user engagement generated by live streaming has posed challenges to the existing regulatory frameworks. In China, the situation of regulating Zhibo (literally ‘live streaming’) is arguably even more complex due to the rapid industrial changes, a mass scale of video content along with the Wanghong Economy, and fragmented internet governance. Drawing on interviews and analysis of regulatory documents, this study investigated the dynamic negotiations among regulatory actors in Chinese live streaming sectors, underscoring that the idea of multiple levels of self‐regulation with minimal state oversight has become the principal strategy for regulating live streaming in a multiactor coordination context. Regulation of the Zhibo is characterized by a conflict between uneven accountability and decentralized regulatory activities in the contemporary regulatory regime.
Ice wedge polygon stability on steep slopes in West Greenland related to temperature and moisture dynamics of the active layer
Authors: Schwarzkopf Katharina , Seitz Steffen , Fritz Michael , Scholten Thomas , Kühn Peter
Published: March 2023

Ice wedge polygons on steep slopes have generally been described as being covered by periglacial sediments and, typically, the active layer on slopes becomes mobile during thaw periods, which can lead to solifluction. In West Greenland close to the ice margin, however, the active layer and ice wedge polygons are stable despite their occurrence on steep slopes with inclinations of ≥30°. We conducted a soil survey (including sampling for soil analyses and radiocarbon dating) in the Umimmalissuaq valley and installed a field station ~4 km east of the current ice margin to monitor soil temperature and water tension at depths of 10, 20 and 35 cm of the active layer on a steep, north‐facing slope in the middle of an ice wedge polygon from 2009 to 2015. Thawing and freezing periods lasted between 2 and 3 months and the active layer was usually completely frozen from November to April. We observed simultaneous and complete water saturation at all three depths of the active layer in one summer for 1 day. The amount of water in the active layer apparently was not enough to trigger solifluction during the summer thaw, even at slope inclinations above 30°. In addition, the dense shrub tundra absorbs most of the water during periods between thawing and freezing, which further stabilizes the slope. This process, together with the dry and continental climate caused by katabatic winds combined with no or limited frost heave, plays a crucial role in determining the stability of these slopes and can explain the presence of large‐scale stable ice wedge polygon networks in organic matter‐rich permafrost, which is about 5,000 years old. This study underlines the importance of soil hydrodynamics and local climate regime for landscape stability and differing intensities of solifluction processes in areas with strong geomorphological gradients and rising air temperatures.
Rational design of mini protein mimicking uricase: Encapsulation in ZIF‐8 for uric acid detection
Authors: Abdul Aziz Siti Fatimah Nur , Rahim Arilla Sri Masayu Abd , Normi Yahaya M. , Alang Ahmad Shahrul Ainliah , Salleh Abu Bakar
Published: March 2023

Five mini proteins mimicking uricase comprising 20, 40, 60, 80, and 100 amino acids were designed based on the conserved active site residues within the same dimer, using the crystal structure of tetrameric uricase from Arthrobacter globiformis (PDB ID: 2yzb) as a template. Based on molecular docking analysis, the smallest mini protein, mp20, shared similar residues to that of native uricase that formed hydrogen bonds with uric acid and was chosen for further studies. Although purified recombinant mp20 did not exhibit uricase activity, it showed specific binding towards uric acid and evinced excellent thermotolerance and structural stability at temperatures ranging from 10°C to 100°C, emulating its natural origin. To explore the potential of mp20 as a bioreceptor in uric acid sensing, mp20 was encapsulated within zeolitic imidazolate framework‐8 (mp20@ZIF‐8) followed by the modification on rGO‐screen printed electrode (rGO/SPCE) to maintain the structural stability. An irreversible anodic peak and increased semicircular arcs of the Nyquist plot with an increase of the analyte concentrations were observed by utilizing cyclic voltammetry and electrochemical impedance spectroscopy (EIS), suggesting the detection of uric acid occurred, which is based on substrate–mp20 interaction.
Domain shuffling of a highly mutable ligand‐binding fold drives adhesin generation across the bacterial kingdom
Authors: Barringer Rob , Parnell Alice E. , Lafita Aleix , Monzon Vivian , Back Catherine R. , Madej Mariusz , Potempa Jan , Nobbs Angela H. , Burston Steven G. , Bateman Alex , Race Paul R.
Published: March 2023

Bacterial fibrillar adhesins are specialized extracellular polypeptides that promote the attachment of bacteria to the surfaces of other cells or materials. Adhesin‐mediated interactions are critical for the establishment and persistence of stable bacterial populations within diverse environmental niches and are important determinants of virulence. The fibronectin (Fn)‐binding fibrillar adhesin CshA, and its paralogue CshB, play important roles in host colonization by the oral commensal and opportunistic pathogen Streptococcus gordonii. As paralogues are often catalysts for functional diversification, we have probed the early stages of structural and functional divergence in Csh proteins by determining the X‐ray crystal structure of the CshB adhesive domain NR2 and characterizing its Fn‐binding properties in vitro. Despite sharing a common fold, CshB_NR2 displays an ~1.7‐fold reduction in Fn‐binding affinity relative to CshA_NR2. This correlates with reduced electrostatic charge in the Fn‐binding cleft. Complementary bioinformatic studies reveal that homologues of CshA/B_NR2 domains are widely distributed in both Gram‐positive and Gram‐negative bacteria, where they are found housed within functionally cryptic multi‐domain polypeptides. Our findings are consistent with the classification of Csh adhesins and their relatives as members of the recently defined polymer adhesin domain (PAD) family of bacterial proteins.
Tezepelumab as add‐on treatment for severe asthma
Authors: Chaplin Steve
Published: March 2023

Tezepelumab (Tezspire) is a new monoclonal antibody therapy for add‐on treatment in adolescents and adults with inadequately controlled severe asthma. This article outlines its mode of action, indication and clinical trial outcomes.
Automated solid‐phase synthesis of metabolically stabilized triazolo‐peptidomimetics
Authors: Guarrochena Xabier , Kaudela Barbara , Mindt Thomas L.
Published: March 2023

The use of 1,4‐disubstituted 1,2,3‐triazoles as trans‐amide bond surrogates has become an important tool for the synthesis of metabolically stabilized peptidomimetics. These heterocyclic bioisosters are generally incorporated into the peptide backbone by applying a diazo‐transfer reaction followed by CuAAC (click chemistry) with an α‐amino alkyne. Even though the manual synthesis of backbone‐modified triazolo‐peptidomimetics has been reported by us and others, no procedure has yet been described for an automated synthesis using peptide synthesizers. In order to efficiently adapt these reactions to an automated setup, different conditions were explored, putting special emphasis on the required long‐term stability of both the diazo‐transfer reagent and the Cu(I) catalyst in solution. ISA·HCl is the reagent of choice to accomplish the diazo‐transfer reaction; however, it was found instable in DMF, the most commonly used solvent for SPPS. Thus, an aqueous solution of ISA·HCl was used to prevent its degradation over time, and the composition in the final diazo‐transfer reaction was adjusted to preserve suitable swelling conditions of the resins applied. The CuAAC reaction was performed without difficulties using [Cu (CH3CN)4]PF6 as a catalyst and TBTA as a stabilizer to prevent oxidation to Cu(II). The optimized automated two‐step procedure was applied to the synthesis of structurally diverse triazolo‐peptidomimetics to demonstrate the versatility of the developed methodology. Under the optimized conditions, five triazolo‐peptidomimetics (8–5 amino acid residues) were synthesized efficiently using two different resins. Analysis of the crude products by HPLC‐MS revealed moderate to good purities of the desired triazolo‐peptidomimetics (70–85%). The synthesis time ranged between 9 and 12.5 h.