bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Cathode Materials for Protonic Ceramic Fuel Cells: Recent Progress and Future Perspectives
Authors: Wang Ning , Tang Chunmei , Du Lei , Zhu Ruijie , Xing Lixin , Song Zhongqian , Yuan Baoyin , Zhao Lei , Aoki Yoshitaka , Ye Siyu
Published: July 2022

Intermediate‐temperature proton ceramic fuel cells (PCFCs)–a promising power generation technology–have attracted significant attention in recent years because of their unique advantages over conventional high‐temperature solid oxide fuel cells and low‐temperature proton exchange membrane fuel cells. The cathodes of PCFCs simultaneously require efficient channels for proton, oxide‐ion, and electron transfer; therefore, designing and engineering cathode materials with tailorable H+, O2−, and e− conductivities are crucial for improving PCFC performance. Despite significant efforts and critical progress in this field, exploring the desired cathode materials remains challenging. This review provides a comprehensive and critical overview of oxide materials for PCFC cathodes, particularly triple H+/O2−/e− conductors. Their proton uptake, conduction mechanisms, and structure–property relationships are focused on to guide future material design. In addition, the electrochemical performance of these cathode materials in PCFCs is discussed and the electrochemical performance gaps among PCFCs with different types of cathode materials are defined. Finally, perspectives on the development of high‐performance PCFCs are proposed.
Pharmacological Chaperones for GCase that Switch Conformation with pH Enhance Enzyme Levels in Gaucher Animal Models
Authors: Santana Andrés G. , Robinson Kyle , Vickers Chelsea , Deen Matthew C. , Chen Hong‐Ming , Zhou Stephen , Dai Ben , Fuller Maria , Boraston Alisdair B. , Vocadlo David J. , Clarke Lorne A. , Withers Stephen G.
Published: July 2022

Gaucher disease is a lysosomal storage disorder caused by mutations which destabilize the native folded form of GCase, triggering degradation and ultimately resulting in low enzyme activity. Pharmacological chaperones (PCs) which stabilize mutant GCase have been used to increase lysosomal activity through improving trafficking efficiency. By engineering their inherent basicity, we have synthesized PCs that change conformation between the ER and the lysosomal environment, thus weakening binding to GCase after its successful trafficking to the lysosome. NMR studies confirmed the conformational change while X‐ray data reveal bound conformations and binding modes. These results were further corroborated by cell studies showing increases in GCase activity when using the pH‐switchable probe at low dosing. Preliminary in vivo assays with humanized mouse models of Gaucher showed enhanced GCase activity levels in relevant tissues, including the brain, further supporting their potential.
Recent Advances in Host‐Guest Supramolecular Hydrogels for Biomedical Applications
Authors: Wang Suxi , Ong Pin Jin , Liu Songlin , Thitsartarn Warintorn , Tan Maureen Janet Beng Hoon , Suwardi Ady , Zhu Qiang , Loh Xian Jun
Published: July 2022

The recognition‐directed host‐guest interaction is recognized as a valuable tool for creating supramolecular polymers. Functional hydrogels constructed through the dynamic and reversible host‐guest complexation are endowed with a great many appealing features, such as superior self‐healing, injectability, flexibility, stimuli‐responsiveness and biocompatibility, which are crucial for biological and medicinal applications. With numerous topological structures and host‐guest combinations established previously, recent breakthroughs in this area mostly focus on further improvement and fine‐tuning of various properties for practical utilizations. The current contribution provides a comprehensive overview of the latest developments in host‐guest supramolecular hydrogels, with a particular emphasis on the innovative molecular‐level design strategies and hydrogel formation methodologies targeting at a wide range of active biomedical domains, including drug delivery, 3D printing, wound healing, tissue engineering, artificial actuators, biosensors, etc. Furthermore, a brief conclusion and discussion on the steps forward to bring these smart hydrogels to clinical practice is also presented.
Multiepitope‐based vaccine design by exploring antigenic potential among leptospiral lipoproteins using comprehensive immunoinformatics and structure‐based approaches
Authors: Kumar Pankaj , Shiraz Mohd. , Akif Mohd.
Published: July 2022

Leptospirosis is a tropical and globally neglected zoonotic disease caused by pathogenic spirochetes, Leptospira. Although the disease has been studied for decades, a potent or effective vaccine is not available so far. Efforts are being made to design an efficient vaccine candidate using different approaches. Immunoinformatics approaches have been proven to be promising in terms of time and cost. Here, we used immunoinformatics and structure‐based approaches to evaluate antigenic B‐ and T‐cell epitopes present on the leptospiral lipoproteins (LipL). The promiscuous overlapping epitopes (B‐cell, T‐cell, interferon (IFN)‐γ positive, and non‐allergens), which can induce humoral, cell‐mediated, and innate immunity, were selected to generate a multiepitope chimeric vaccine. To enhance the vaccine immunogenicity, a Toll‐like receptor (TLR) agonist was fused to the vaccine with a suitable linker. The chimeric vaccine structure was predicted for molecular docking studies with immune receptors. Moreover, the stability of the vaccine–immune receptor complexes was analyzed by normal mode analysis (NMA). The potency of the vaccine construct was predicted by the immune simulation tool. The study provides additional information toward constructing peptide‐based chimeric vaccines  against Leptospira.
What topics should or should not be included in software security education—Qualitative content analysis
Authors: Ebad Shouki A.
Published: July 2022

Software security education is still not preparing students for the types of high‐skilled technical roles that represent the most severe workforce shortage. Recognizing this, academia has begun redefining the knowledge area concepts of software security curricula to meet the current workforce shortage. This article studies the software security courses in Arab Gulf academic programs and benchmarks their descriptions with the corresponding knowledge area from cybersecurity Curricula (CSEC). 2017, the first set of global cybersecurity curricular guidelines. Using content analysis, six concepts or essentials are investigated: security requirements, secure design principles, secure source code, analysis and testing, patch, and ethics. It was found that no course follows all the CSEC. 2017 essentials. The analysis and testing essential were considered by all courses, and security after deployment, including the patch essential, needs more attention because it was not included in any course. Similarly, the security requirements and ethics essentials were also considered by a few courses. However, software success depends on requirements, and ethics has become critical in the cybersecurity and information assurance fields that depend on law and forensics. The secure source code essential was covered by most courses. The well‐known types of code attacks were covered, and over half of the courses discussed secure design principles essential. However, security by design is an emerging development philosophy. The article discussed observations and recommendations that will assist program managers and their staff in making effective decisions about the essentials and concepts that should be included when they are developing the software security curriculum.
DDX24 promotes metastasis by regulating RPL5 in non‐small cell lung cancer
Authors: Hu Xinyan , Li Fangfang , Zhou Yulan , Gan Hairun , Wang Tiancheng , Li Luting , Long Haoyu , Li Bing , Pang Pengfei
Published: July 2022

Purpose

Non‐small cell lung cancer (NSCLC) is a leading cause of cancer death, and metastasis is a crucial determinant of increased cancer mortality. DDX24 has garnered increased attention due to its correlation with tumorigenesis and malignant progression. However, the correlation between DDX24 and NSCLC remains unclear.

Methods

DDX24 expression in NSCLC tissues and survival rate of patients was analyzed using bioinformatic analysis. Transwell assays, wound‐healing assays, and tail vein lung colonization models were employed to determine the role of DDX24 in migration and invasion in vitro and in vivo. We searched for DDX24‐interacting proteins using co‐immunoprecipitation followed by mass spectroscopy and verified the interaction. The influence of DDX24 on RPL5 expression and ubiquitination was examined using protein stability assays.

Results

DDX24 expression was upregulated in NSCLC cell lines and tumors of patients, particularly those with high tumor grades. A high DDX24 level was also correlated with a poor prognosis. DDX24 upregulation enhanced the migration and invasion ability of NSCLC cells, whereas its downregulation had the opposite effects. In vivo xenograft experiments confirmed that tumors with high DDX24 expression had higher metastatic abilities. The interaction between DDX24 and RPL5 promoted its ubiquitination and destabilized it.

Conclusions

DDX24 acted as a pro‐tumorigenic factor and promoted metastasis in NSCLC. DDX24 interacted with RPL5 to promote its ubiquitination and degradation. As a result, targeting DDX24/RPL5 axis may provide a novel potential therapeutic strategy for NSCLC.
Therapists' experiences of a brief case formulation and alliance focused pre‐treatment training session (CALL)
Authors: Jacobsen Celia Faye , Mathiesen Birgit Bork , Poulsen Stig , Lunn Susanne , Dahlgaard Mads , Nielsen Jan
Published: July 2022

Objective

A general lack of supervision outcome studies and new advancements within therapist training methods inspired us to develop a randomised controlled trial, Case formulation and ALLiance (CALL), testing the efficacy of a brief pre‐treatment training session. CALL combines generic case formulation and alliance principles with the supervision of a specific client. This qualitative study acts as a preliminary to the randomised controlled trial and aims to explore psychologists' experiences of participating in CALL.

Method

Semi‐structured interviews were conducted with seven psychologists in private practice, who participated in CALL between January and May 2020. The transcribed interviews were analysed using thematic analysis.

Results

The psychologists described CALL as a clinically useful and collegial experience but simultaneously conveyed a lack of recollection of the training session and doubts as to its enduring utilisation.

Conclusion

CALL has the potential to positively influence the process and outcome of therapy through the fostering of case formulation and alliance management skills, as well as a strong supervisory alliance. However, the familiar content or brief format of the session, and participants' memory bias, may have limited the utilisation and recall of the intervention.
An accidental emamectin benzoate poisoning in child: A case report
Authors: Yadav Gopal Kumar , Rohita Dipesh Kumar , Mandal Krishna Chandra , Paudel Binod , Devkot Ashok Raj
Published: July 2022

We report a case of accidental Emamectin Benzoate poisoning in a six‐year‐old child resulting in nausea, vomiting, abdominal pain, and confusion. We did vigorous gastric lavage with saline, activated charcoal, and coconut oil. The other supportive treatment improved the outcome of the patient with complete resolution of symptoms.
Intraoperative recurrent laryngeal nerve monitoring in unconventional thyroid surgery
Authors: Filippo Carta , Valeria Marrosu , Valeria Pinto , Melania Tatti , Bontempi Mauro , Cinzia Mariani , Roberto Puxeddu
Published: July 2022

The most common surgical risk after total thyroidectomy remains the recurrent laryngeal nerve (RLN) injury. Nowadays, the use of intraoperative nerve monitoring systems (IONM) such as the endotracheal tube‐based is recommended to prevent RLN palsy. The use of the nerve monitoring is standardized by dedicated guidelines on the basis of a normal laryngeal anatomy, but previous head and neck surgical procedures may complicate its application. The authors herewith present a case of a non‐conventional use of endotracheal tube‐based IONM in a 72‐year‐old patient who underwent to a second‐stage total thyroidectomy for metastatic papillary cancer incidentally detected after an open partial horizontal laryngectomy (OPHL) extended to one arytenoid (Type IIa + ary left) for squamous cell carcinoma. The use of the endotracheal tube‐based IONM in such particular case where the function of the only remaining arytenoid had to be absolutely preserved was effective in avoiding the RLN accidental injury. The authors reviewed the non‐traditional use of IONM and described the procedure in case of thyroidectomy in patients previously treated by OPHL.
The importance of inspection in clinical cardiology: Frank's sign
Authors: Bazoukis George , Papadatos Stamatis S. , Varrias Dimitrios , Tse Gary
Published: July 2022

The Frank's sign (FS) is a diagonal earlobe crease running from the tragus to the edge of the auricle. In this case, we describe a 71 years‐old male patient with FS who presented to the emergency department complaining of epigastric pain. A non‐ST elevation myocardial infarction was diagnosed.
Discovery of Complex Binding and Reaction Mechanisms from Ternary Gases in Rare Earth Metal–Organic Frameworks
Authors: Christian Matthew S. , Nenoff Tina M. , Rimsza Jessica M.
Published: July 2022

Understanding the selectivity of metal–organic frameworks (MOFs) to complex acid gas streams will enable their use in industrial applications. Herein, ab initio molecular dynamic simulations (AIMD) were used to simulate ternary gas mixtures (H2O‐NO2‐SO2) in rare earth 2,5‐dihydroxyterephthalic acid (RE‐DOBDC) MOFs. Stronger H2O gas‐metal binding arose from thermal vibrations in the MOF sterically hindering access of SO2 and NO2 molecules to the metal sites. Gas‐gas and gas‐linker interactions within the MOF framework resulted in the formation of multiple secondary gas species including HONO, HNO2, NOSO, and HNO3−. Four gas adsorption sites were identified along with a new de‐protonation reaction mechanism not observable through experiment. This study not only provides valuable information on competitive gas binding energies in the MOF, it also provides important chemical insights into transient chemical reactions and mechanisms.
Drivers of racial, regional, and socioeconomic disparities in late‐stage breast cancer mortality
Authors: Moubadder Leah , Collin Lindsay J. , Nash Rebecca , Switchenko Jeffrey M. , Miller‐Kleinhenz Jasmine M. , Gogineni Keerthi , Ward Kevin C. , McCullough Lauren E.
Published: July 2022

Background

The authors identified tumor, treatment, and patient characteristics that may contribute to differences in breast cancer (BC) mortality by race, rurality, and area‐level socioeconomic status (SES) among women diagnosed with stage IIIB–IV BC in Georgia.

Methods

Using the Georgia Cancer Registry, 3084 patients with stage IIIB–IV primary BC (2013–2017) were identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing mortality among non‐Hispanic Black (NHB) versus non‐Hispanic White (NHW), residents of rural versus urban neighborhoods, and residents of low‐ versus high‐SES neighborhoods by tumor, treatment, and patient characteristics. The mediating effects of specific characteristics on the association between race and BC mortality were estimated.

Results

Among the study population, 41% were NHB, 21% resided in rural counties, and 72% resided in low SES neighborhoods. The authors observed mortality disparities by race (HR, 1.27; 95% CI, 1.13, 1.41) and rurality (HR, 1.14; 95% CI, 1.00, 1.30), but not by SES (HR, 1.04; 95% CI, 0.91, 1.19). In the stratified analyses, racial disparities were the most pronounced among women with HER2 overexpressing tumors (HR, 2.30; 95% CI, 1.53, 3.45). Residing in a rural county was associated with increased mortality among uninsured women (HR, 2.25; 95% CI, 1.31, 3.86), and the most pronounced SES disparities were among younger women (<40 years: HR, 1.46; 95% CI, 0.88, 2.42).

Conclusions

There is considerable variation in racial, regional, and socioeconomic disparities in late‐stage BC mortality by tumor, treatment, and patient characteristics.
Alpha‐Nickel Hydroxide Coating of Metallic Nickel for Enhanced Alkaline Hydrogen Evolution
Authors: Xue Song , Liang Yunchang , Hou Shujin , Zhang Yajing , Jiang Heqing
Published: July 2022

In this work, alkaline hydrogen evolution reaction (HER) processes of three typical nickel‐based electrocatalysts [i. e., Ni, α‐Ni(OH)2, and β‐Ni(OH)2] were investigated to probe critical factors that determine the activity and durability. The HER activity trend was observed as Ni≫α‐Ni(OH)2>β‐Ni(OH)2, likely attributed to a synergy between metallic Ni and Ni(OH)2 components on the Ni surface and fast water dissociation kinetics on the α‐Ni(OH)2 surface. With the HER proceeding, the metallic Ni surface, however, gradually became α‐Ni(OH)2, and α‐Ni(OH)2 surface ultimately transformed into β‐phase, leading to a dramatic activity decrease of Ni electrodes. Therefore, Ni electrodes were coated with α‐Ni(OH)2 nanosheets to slow down the nickel hydroxylation and optimize the surface ratio of Ni(OH)2 to metallic Ni. This simple coating procedure enhanced both activity and durability of Ni electrocatalysts.
Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2
Authors: Zhu Yingzi , Gu Heng , Yang Lu , Li Na , Chen Qiuyue , Kang Danqing , Lin Shengyan , Jing Yukai , Jiang Panpan , Chen Qianglin , Luo Li , Liu Ju , Chang Jiang , Li Zhenzhen , Wang Yi , Dai Xin , Miller Heather , Westerberg Lisa S. , Park Chan‐Sik , Kubo Masato , Gong Quan , Dong Lingli , Liu Chaohong
Published: July 2022

Background

CCR2 is involved in maintaining immune homeostasis and regulating immune function. This study aims to elucidate the mechanism by which CCR2 regulates B‐cell signalling.

Methods

In Ccr2‐knockout mice, the development and differentiation of B cells, BCR proximal signals, actin movement and B‐cell immune response were determined. Besides, the level of CCR2 in PBMC of SLE patients was analysed by bioinformatics.

Results

CCR2 deficiency reduces the proportion and number of follicular B cells, upregulates BCR proximal signalling and enhances the oxidative phosphorylation of B cells. Meanwhile, increased actin filaments aggregation and its associated early‐activation events of B cells are also induced by CCR2 deficiency. The MST1/mTORC1/STAT1 axis in B cells is responsible for the regulation of actin remodelling, metabolic activities and transcriptional signalling, specific MST1, mTORC1 or STAT1 inhibitor can rescue the upregulated BCR signalling. Glomerular IgG deposition is obvious in CCR2‐deficient mice, accompanied by increased anti‐dsDNA IgG level. Additionally, the CCR2 expression in peripheral B cells of SLE patients is decreased than that of healthy controls.

Conclusions

CCR2 can utilise MST1/mTORC1/STAT1 axis to regulate BCR signalling. The interaction between CCR2 and BCR may contribute to exploring the mechanism of autoimmune diseases.
What can occupancy models gain from time‐to‐detection data?
Authors: Priyadarshani Dinusha , Altwegg Res , Lee Alan T. K. , Hwang Wen‐Han
Published: July 2022

The time taken to detect a species during site occupancy surveys contains information about the observation process. Accounting for the observation process leads to better inference about site occupancy. We explore the gain in efficiency that can be obtained from time‐to‐detection (TTD) data and show that this model type has a significant benefit for estimating the parameters related to detection intensity. However, for estimating occupancy probability parameters, the efficiency improvement is generally very minor. To explore whether TTD data could add valuable information when detection intensities vary between sites and surveys, we developed a mixed exponential TTD occupancy model. This new model can simultaneously estimate the detection intensity and aggregation parameters when the number of detectable individuals at the site follows a negative binomial distribution. We found that this model provided a much better description of the occupancy patterns than conventional detection/nondetection methods among 63 bird species data from the Karoo region of South Africa. Ignoring the heterogeneity of detection intensity in the TTD model generally yielded a negative bias in the estimated occupancy probability. Using simulations, we briefly explore study design trade offs between numbers of sites and surveys for different occupancy modeling strategies.
Revealing the Multifunctional Electrocatalysis of Indium‐Modulated Phthalocyanine for High‐Performance Lithium‐Sulfur Batteries
Authors: Guo Yang , Jin Zhaoqing , Lu Jianhao , Wang Zilong , Song Zihao , Wang Anbang , Wang Weikun , Huang Yaqin
Published: July 2022

The sluggish kinetics of complicated multiphase conversions and the severe shuttling effect of lithium polysulfides (LiPSs) significantly hinder the applications of Li‐S battery, which is one of the most promising candidates for the next‐generation energy storage system. Herein, a bifunctional electrocatalyst, indium phthalocyanine self‐assembled with carbon nanotubes (InPc@CNT) composite material, is proposed to promote the conversion kinetics of both reduction and oxidation processes, demonstrating a bidirectional catalytic effect on both nucleation and dissolution of Li2S species. The theoretical calculation shows that the unique electronic configuration of InPc@CNT is conducive to trapping soluble polysulfides in the reduction process, as well as the modulation of electron transfer dynamics also endows the dissolution of Li2S in the oxidation reaction, which will accelerate the effectiveness of catalytic conversion and facilitate sulfur utilization. Moreover, the InPc@CNT modified separator displays lower overpotential for polysulfide transformation, alleviating polarization of electrode during cycling. The integrated spectroscopy analysis, HRTEM, and electrochemical study reveal that the InPc@CNT acts as an efficient multifunctional catalytic center to satisfy the requirements of accelerating charging and discharging processes. Therefore, the Li–S battery with InPc@CNT‐modified separator obtains a discharge‐specific capacity of 1415 mAh g−1 at a high rate of 0.5 C. Additionally, the 2 Ah Li–S pouch cells deliver 315 Wh kg−1 and achieved 80% capacity retention after 50 cycles at 0.1 C with a high sulfur loading of 10 mg cm−2. Our study provides a practical method to introduce bifunctional electrocatalysts for boosting the electrochemical properties of Li–S batteries.
Electrochemical Detection of Artemisinin Using Cobalt Sulphide/Reduced Graphene Oxide Nanocomposite
Authors: Kwabena Adu Darko , Nate Zondi , Alake John , Wisdom Ike Blessing , Chauhan Ruchika , Karpoormath Rajshekhar
Published: July 2022

Solvothermally synthesized cobalt sulphide/reduced graphene oxide (CoS/rGO) was used to fabricate an electrochemical sensor for detection of artemisinin. Microscopic techniques were used to characterize CoS/rGO nanocomposite. The electrochemical sensor was fabricated by modifying the surface of glassy carbon electrode with CoS/rGO nanocomposite. [Fe(CN)6]3−/4− was used as a mediator to aid oxidation of artemisinin. Differential pulse voltammetric technique was used for the detection of artemisinin. A linear range of 30–100 μM was used. Experimentally, a detection limit of 0.5 μM was obtained. Therefore, the developed sensor can be used for quality control of artemisinin.
A cross‐sectional study of COVID‐19 vaccination patterns among patients with epilepsy in Hong Kong
Authors: Chan Charlie CH , Choi Chun‐Ho , Lui Wai Ting , Ip Bonaventure , Ma Karen KY , Ma Sze Ho , Fan Florence SY , Au Lisa , Lau Alexander , Chan Anne YY , Ip Vincent , Soo Yannie , Leung Thomas , Mok Vincent , Leung Howan
Published: July 2022

Objective

As Hong Kong faced the 5th wave of the COVID‐19 pandemic, the facilitators and hurdles toward effective vaccination is important for healthcare professionals to understand the vaccination gap among patients with epilepsy.

Methods

A cross‐sectional, pragmatic study of COVID‐19 vaccination was performed at a tertiary epilepsy center with regards to patterns of vaccination and any unusually high rate of adverse events. Patients having recent visits at the epilepsy center (4 months) had their anonymized electronic linkage records examined 12 months after the inception of vaccination program for types of vaccines, seizure demographics, and adverse events following immunization (AEFI).

Results

A total of 200 patients with epilepsy and their anonymized data were analyzed. The vaccine uptake was approximately 60% of that of the general population. Twice as many patients with epilepsy chose to receive mRNA vaccine as compared with inactivated vaccine. The proportion of patients who kept up‐to‐date with all available dosing was 7%. Patients with epilepsy with genetic etiology were least likely to receive vaccination (13/38, 34%, P = .02). There was no unreasonably high rate of unacceptable side effects after vaccination among patients with epilepsy. Only 3 patients reported worsening of seizures without meeting the criteria for AEFI. Refractory epilepsy, allergy to antiseizure medications and elder age (≥65) did not confer any significant difference in vaccination patterns or adverse effects.

Significance

A vaccination gap exists among epilepsy patients which calls for actionable strategies for improving vaccine uptake, including education and outreach programs.
Endoscopic trans‐lateral oropharyngeal wall approach to the petrous apex and the petroclival region
Authors: Li Lifeng , Xu Hongbo , London Nyall R. , Carrau Ricardo L. , Jin Yonggang , Chen Xiaohong
Published: July 2022

Background

A trans‐lateral oropharyngeal wall approach (TLOWA) to the petrous apex has not been previously defined. This study aims to assess the feasibility of a TLOWA for surgical access to the petrous apex and the petroclival region.

Methods

An endoscopic TLOWA for exposure of the petrous apex and petroclival region was performed on five cadaveric specimens (10 sides). Associated anatomical landmarks were defined, and the strategies for maximal exposure of the internal carotid artery (ICA) were explored.

Results

Via a TLOWA, the parapharyngeal ICA was widely exposed in all 10 sides. Following transection of the Eustachian tube, the inferior petrous apex and petroclival region could be sufficiently exposed. After drilling the anteroinferior bony canal, the horizontal petrous ICA, foramen lacerum, and the paraclival ICA could be adequately revealed.

Conclusion

The TLOWA may provide an alternative corridor for access to the petrous apex and the petroclival region. The parapharyngeal, petrous, lower paraclival ICAs, and the foramen lacerum could be adequately exposed via the TLOWA.
Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry‐based metabolomics: A case‐control study nested in the Northern Sweden Health and Disease Study
Authors: Östman Johnny R. , Pinto Rui C. , Ebbels Timothy M. D. , Thysell Elin , Hallmans Göran , Moazzami Ali A.
Published: July 2022

Prostate cancer (PCa) is the most common cancer form in males in many European and American countries, but there are still open questions regarding its etiology. Untargeted metabolomics can produce an unbiased global metabolic profile, with the opportunity for uncovering new plasma metabolites prospectively associated with risk of PCa, providing insights into disease etiology. We conducted a prospective untargeted liquid chromatography‐mass spectrometry (LC‐MS) metabolomics analysis using prediagnostic fasting plasma samples from 752 PCa case‐control pairs nested within the Northern Sweden Health and Disease Study (NSHDS). The pairs were matched by age, BMI, and sample storage time. Discriminating features were identified by a combination of orthogonal projection to latent structures‐effect projections (OPLS‐EP) and Wilcoxon signed‐rank tests. Their prospective associations with PCa risk were investigated by conditional logistic regression. Subgroup analyses based on stratification by disease aggressiveness and baseline age were also conducted. Various free fatty acids and phospholipids were positively associated with overall risk of PCa and in various stratification subgroups. Aromatic amino acids were positively associated with overall risk of PCa. Uric acid was positively, and glucose negatively, associated with risk of PCa in the older subgroup. This is the largest untargeted LC‐MS based metabolomics study to date on plasma metabolites prospectively associated with risk of developing PCa. Different subgroups of disease aggressiveness and baseline age showed different associations with metabolites. The findings suggest that shifts in plasma concentrations of metabolites in lipid, aromatic amino acid, and glucose metabolism are associated with risk of developing PCa during the following two decades.
Implementing and reflecting on the Veterinary Graduate Development Programme
Authors: Richards Kate
Published: July 2022

This article outlines the benefits that the Veterinary Graduate Development Programme (VetGDP) brings to practices and how the programme supports the newest veterinary sector cohort with their clinical and professional skills. It also includes first‐hand experiences from two newly graduated veterinary surgeons, Isabelle Pearce and Stephanie‐Rae Flicker, who discuss how the VetGDP has helped them to develop their skills and confidence in their first roles following graduation.
Radiofrequency impedance monitoring of the biological tissues under local heating by optical radiation
Authors: Kovalenko Nikita , Sovin Kirill , Malikova Tatiana , Smirnov Artur , Anpilov Vladimir , Ryabushkin Oleg
Published: July 2022

Development of methods for simultaneous control of state of biological tissues during optical treatment is the important tasks in laser surgery. We introduce a novel approach for the monitoring of the state of biological tissues in the process of its local heating by optical radiation. It is based on measurements of the electrical radiofrequency impedance kinetics of the sample during irradiation. The obtained data are processed using interconnected mathematical modeling of corresponding thermodynamic, optical and electrical problems. Experimental applications of this approach, represented in the paper, reveal its high sensitivity, repeatability and consistency with the model. The introduced method can be used for the selection and optimization of radiation parameters of medical laser sources as an alternative or an addition to histological techniques. Radiofrequency impedance measurement can be used directly in the course of surgical operations for monitoring the treated tissues state, including its temperature and degree of damage.
Moving towards a novel therapeutic strategy for hyperammonemia that targets glutamine metabolism
Authors: Fukui Kaori , Takahashi Tomoyuki , Matsunari Hitomi , Uchikura Ayuko , Watanabe Masahito , Nagashima Hiroshi , Ishihara Naotada , Kakuma Tatsuyuki , Watanabe Yoriko , Yamashita Yushiro , Yoshino Makoto
Published: July 2022

Patients with urea cycle disorders intermittently develop episodes of decompensation with hyperammonemia. Although such an episode is often associated with starvation and catabolism, its molecular basis is not fully understood. First, we attempted to elucidate the mechanism of such starvation‐associated hyperammonemia. Using a mouse embryonic fibroblast (MEF) culture system, we found that glucose starvation increases ammonia production, and that this increase is associated with enhanced glutaminolysis. These results led us to focus on α‐ketoglutarate (AKG), a glutamate dehydrogenase inhibitor, and a major anaplerotic metabolite. Hence, we sought to determine the effect of dimethyl α‐ketoglutarate (DKG), a cell‐permeable AKG analog, on MEFs and found that DKG mitigates ammonia production primarily by reducing flux through glutamate dehydrogenase. We also verified that DKG reduces ammonia in an NH4Cl‐challenged hyperammonemia mouse model and observed that DKG administration reduces plasma ammonia concentration to 22.8% of the mean value for control mice that received only NH4Cl. In addition, we detected increases in ornithine concentration and in the ratio of ornithine to arginine following DKG treatment. We subsequently administered DKG intravenously to a newborn pig with hyperammonemia due to ornithine transcarbamylase deficiency and found that blood ammonia concentration declined significantly over time. We determined that this effect is associated with facilitated reductive amination and glutamine synthesis. Our present data indicate that energy starvation triggers hyperammonemia through enhanced glutaminolysis and that DKG reduces ammonia accumulation via pleiotropic mechanisms both in vitro and in vivo. Thus, cell‐permeable forms of AKG are feasible candidates for a novel hyperammonemia treatment.
Campylobacter jejuniinduces differentiation of human neutrophils to the CD16hi/CD62Llo subtype
Authors: Dolislager Carolina G , Callahan Sean M , Donohoe Dallas R , Johnson Jeremiah G
Published: July 2022

The discovery of neutrophil subtypes has expanded what is known about neutrophil functions, yet there is still much to learn about the role of these subtypes during bacterial infection. We investigated whether Campylobacter jejuni induced differentiation of human neutrophils into the hypersegmented, CD16hi/CD62Llo subtype. In addition, we investigated whether C. jejuni-dependent differentiation of this neutrophil subtype induced cancer-promoting activities of human T cells and colonocytes, which were observed in other studies of hypersegmented, CD16hi/CD62Llo neutrophils. We found that C. jejuni causes a significant shift in human neutrophil populations to the hypersegmented, CD16hi/CD62Llo subtype and that those populations exhibit delayed apoptosis, elevated arginase-1 expression, and increased reactive oxygen species production. Furthermore, incubation of C. jejuni-infected neutrophils with human T cells resulted in decreased expression of the ζ-chain of the TCR, which was restored upon supplementation with exogenous l-arginine. In addition, incubation of C. jejuni-infected neutrophils with human colonocytes resulted in increased HIF-1α stabilization and NF-κB activation in those colonocytes, which may result in the up-regulation of protumorigenic genes.
q value and parent energy optimization using a low‐voltage ionization approach increases resolution in linear ion trap mass spectrometry
Authors: Madama Simone , Falletta Ermelinda , Malvandi Amir Mohammad , Arzoni Kevin , Brogna Carlo , Varelli Marco , Bertelli Matteo , Conti Matteo , Larini Martina , Guidugli Federico , Traldi Pietro , Cristoni Simone
Published: July 2022

In this work, the isolation step in the linear ion trap was performed using different “q values” conditions at a low collision‐induced dissociation (CID) energy leading to the parent ion resolution improvements, reasonably due to better ion energy distribution. According to the results, we obtained a greater resolution and mass accuracy operating in both traditional electrospray and low voltage ionization near the q value = 0.778 and with a CID energy of 10%. This effect was evaluated with low‐molecular‐mass compounds (skatole and arginine). The proposed optimization yielded a superior instrument performance without adding technological complexity to mass spectrometry analyses.
Separation and characterization of bovine milk proteins by capillary electrophoresis‐mass spectrometry
Authors: Ghafoori Zahra , Tehrani Tahereh , Pont Laura , Benavente Fernando
Published: July 2022

Protein profiling of major bovine milk proteins (i.e., whey and casein proteins) is of great interest in food science and technology. This complex set of protein proteoforms may vary with breed, genetics, lactation stage, health, and nutritional status of the animal. Current routine methods for bovine milk protein profiling at the intact level are typically based on capillary electrophoresis‐ultraviolet, which does not allow confirming unequivocally the identity of the separated proteins. As an alternative, in this study, we describe for the first time a novel and simple capillary electrophoresis‐mass spectrometry method in positive electrospray ionization mode. Under the optimized conditions, capillary electrophoresis‐mass spectrometry allowed the separation and identification at the intact level of major bovine milk whey and casein proteins in less than 15 min. Furthermore, high‐resolution mass spectrometry confirmed its importance in the reliable characterization of bovine milk protein proteoforms, especially those with slight molecular mass differences, such as β‐casein A1 and A2, which are relevant to unequivocally identify milk with specific β‐casein compositions (e.g., A2A2 milk, which is widely known as A2 milk). This differentiation was not possible by matrix‐assisted laser desorption/ionization mass spectrometry, which provided rapidly and easily a rich but less accurate fingerprint of bovine milk proteins due to the lower mass resolution.
Evaluating Tumor‐Infiltrating Lymphocytes in Breast Cancer
Authors: Jia Yingying , Zhu Yangyang , Li Ting , Song XueWen , Duan Ying , Yang Dan , Nie Fang
Published: July 2022

Objectives

Tumor‐infiltrating lymphocytes (TILs) have emerged as an efficient biomarker predicting treatment response and prognosis of breast cancer (BC). This study aimed to evaluate the association between conventional ultrasound and contrast‐enhanced ultrasound (CEUS) imaging features with TIL levels in invasive BC patients.

Methods

We retrospectively included 267 women with invasive BC who had undergone conventional ultrasound and CEUS. Patients were divided into low (≤10%) and high (>10%) TIL groups. Conventional ultrasound and CEUS features were analyzed by two sonographers. The associations between the TIL levels and imaging features were evaluated.

Results

Of the 267 patients, 122 with high TILs and 145 with low TIL levels. High TIL tumors were more likely to have a circumscribed margin, oval or round shape, and enhanced posterior echoes on ultrasonography (p < 0.05). In contrast, low TIL tumors were more likely to have an irregular shape, un‐circumscribed, indistinct and spiculated margin (p < 0.05). In CEUS, high TIL tumors showed a more regular shape, clearer margin, more homogeneous enhancement and higher peak intensity (PI) value (p < 0.05). Logistic analysis indicated that shape, posterior features, PI, and enhanced homogeneity were independent predictors for high TIL tumors. The model combined the four independent predictors have a moderate performance in predicting high TIL tumors with AUC 0.79, sensitivity 0.72, and specificity 0.78.

Conclusions

Conventional ultrasound and CEUS features were associated with TIL levels in invasive BC. Consequently, the results suggested that preoperative conventional ultrasound and CEUS may be a useful noninvasive imaging biomarker for individualized treatment decisions.
A call to integrate health equity into learning health system research training
Authors: Coley R. Yates , Duan Kevin I. , Hoopes Andrea J. , Lapham Gwen T. , Liljenquist Kendra , Marcotte Leah M. , Ramirez Magaly , Schuttner Linnaea
Published: July 2022

In 2016, the Agency for Healthcare Research and Quality (AHRQ) recommended seven domains for training and mentoring researchers in learning health systems (LHS) science. Health equity was not included as a competency domain. This commentary from scholars in the Consortium for Applied Training to Advance the Learning health system with Scholars/Trainees (CATALyST) K12 program recommends that competency domains be extended to reflect growing demands for evidence on health inequities and interventions to alleviate them. We present real‐life case studies from scholars in an LHS research training program that illustrate facilitators, challenges, and potential solutions at the program, funder, and research community‐level to receiving training and mentorship in health equity‐focused LHS science. We recommend actions in four areas for LHS research training programs: (a) integrate health equity throughout the current LHS domains; (b) develop training and mentoring in health equity; (c) establish program evaluation standards for consideration of health equity; and (d) bring forth relevant, extant expertise from the areas of health disparities research, community‐based participatory research, and community‐engaged health services research. We emphasize that LHS research must acknowledge and build on the substantial existing contributions, mainly by scholars of color, in the health equity field.
Global bifurcation results for some fourth‐order nonlinear eigenvalue problem with a spectral parameter in the boundary condition
Authors: Aliyev Ziyatkhan S. , Aliyeva Yagut N.
Published: July 2022

This paper is devoted to the study of global bifurcation from infinity of nontrivial solutions of a nonlinear eigenvalue problem for ordinary differential equations of fourth order with a spectral parameter in the boundary condition. We prove the existence of two families of unbounded continua of nontrivial solutions to this problem, which emanate from bifurcation points in
and possess oscillatory properties of eigenfunctions (and their derivatives) of the corresponding linear problem in some neighborhoods of these bifurcation points.
Clinical acceptability of fully automated external beam radiotherapy for cervical cancer with three different beam delivery techniques
Authors: Rhee Dong Joo , Jhingran Anuja , Huang Kai , Netherton Tucker J. , Fakie Nazia , White Ingrid , Sherriff Alicia , Cardenas Carlos E. , Zhang Lifei , Prajapati Surendra , Kry Stephen F. , Beadle Beth M. , Shaw William , O'Reilly Frederika , Parkes Jeannette , Burger Hester , Trauernicht Chris , Simonds Hannah , Court Laurence E.
Published: July 2022

Purpose

To fully automate CT‐based cervical cancer radiotherapy by automating contouring and planning for three different treatment techniques.

Methods

We automated three different radiotherapy planning techniques for locally advanced cervical cancer: 2D 4‐field‐box (4‐field‐box), 3D conformal radiotherapy (3D‐CRT), and volumetric modulated arc therapy (VMAT). These auto‐planning algorithms were combined with a previously developed auto‐contouring system. To improve the quality of the 4‐field‐box and 3D‐CRT plans, we used an in‐house, field‐in‐field (FIF) automation program. Thirty‐five plans were generated for each technique on CT scans from multiple institutions and evaluated by five experienced radiation oncologists from three different countries. Every plan was reviewed by two of the five radiation oncologists and scored using a 5‐point Likert scale.

Results

Overall, 87%, 99%, and 94% of the automatically generated plans were found to be clinically acceptable without modification for the 4‐field‐box, 3D‐CRT, and VMAT plans, respectively. Some customizations of the FIF configuration were necessary on the basis of radiation oncologist preference. Additionally, in some cases, it was necessary to renormalize the plan after it was generated to satisfy radiation oncologist preference.

Conclusion

Approximately, 90% of the automatically generated plans were clinically acceptable for all three planning techniques. This fully automated planning system has been implemented into the radiation planning assistant for further testing in resource‐constrained radiotherapy departments in low‐ and middle‐income countries.
Reproducibility of rapid multi‐parameter mapping at 3T and 7T with highly segmented and accelerated 3D‐EPI
Authors: Wang Difei , Ehses Philipp , Stöcker Tony , Stirnberg Rüdiger
Published: July 2022

Purpose

Quantitative multi‐parameter mapping (MPM) has been shown to provide good longitudinal and cross‐sectional reproducibility for clinical research. Unfortunately, acquisition times (TAs) are typically infeasible for routine scanning at high resolutions.

Methods

A fast whole‐brain MPM protocol based on interleaved multi‐shot 3D‐EPI with controlled aliasing (SC‐EPI) at 3T and 7T is proposed and compared with MPM using a standard spoiled gradient echo (FLASH) sequence. Four parameters (R1, PD, , and MTsat) were measured in less than 3 min at 1 mm isotropic resolution. Five subjects went through the same scanning sessions twice at each scanner. The intra‐subject coefficient of variation (scan–rescan) (CoV) was estimated for each protocol and scanner to assess the longitudinal reproducibility.

Results

At 3T, the CoV of SC‐EPI ranged between 1.2%–4.8% for PD and R1, 2.8%–10.6% for and MTsat, which was comparable with FLASH (0.6%–4.9% for PD and R1, 2.6%–11.3% for and MTsat). At 7T, where the SC‐EPI TA was reduced to ∼2 min, the CoV of SC‐EPI (1.4%–10.6% for PD, R1, and ) was 1.2–2.4 times larger than the CoV of FLASH (1.0%–15%) and MTsat showed much higher variability across subjects. The SC‐EPI‐MPM protocol at 3T showed high reproducibility and yielded stable quantitative maps at a clinically feasible resolution and scan time, whereas at 7T, MT saturation homogeneity needs to be improved.

Conclusion

SC‐EPI‐based MPM is feasible as an additional MRI modality in clinical or population studies where the parameters offer great potential as biomarkers.
Glucagon‐like peptide‐1, glucose‐dependent insulinotropic polypeptide, and glucagon receptor poly‐agonists: a new era in obesity pharmacotherapy
Authors: Malik Is‐haq O. , Petersen Max C. , Klein Samuel
Published: July 2022

Achieving successful long‐term weight loss with lifestyle modification in people with obesity is difficult and underscores the need for effective pharmacotherapy. Since 1947, a total of 18 medications have been approved by the US Food and Drug Administration for treating obesity; however, only 5 remain available for long‐term use in the US. Semaglutide, a glucagon‐like peptide‐1 (GLP‐1) receptor agonist approved in 2021, demonstrated much greater weight loss than previous medications, which stimulated the development of poly‐agonists that combine GLP‐1 receptor agonism with glucose‐dependent insulinotropic polypeptide (GIP) and glucagon receptor agonism. The potential of this approach was recently demonstrated by the extraordinary weight loss achieved by tirzepatide, a GLP‐1/GIP receptor dual agonist. The therapeutic efficacy of poly‐agonists is likely to change the treatment paradigm for obesity. However, the use of medications for obesity, as for other chronic diseases, will likely require lifelong treatment, which makes it important to analyze the long‐term efficacy, safety, and economic implications of chronic pharmacotherapy.