bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Tags in One Probe: Combining Fluorescence‐ and Biotin‐based Detection of the Trypanosomal Cysteine Protease Rhodesain
Authors: Lemke Carina , Jílková Adéla , Ferber Dominic , Braune Annett , On Anja , Johe Patrick , Zíková Alena , Schirmeister Tanja , Mareš Michael , Horn Martin , Gütschow Michael
Published: July 2022

Rhodesain is the major cysteine protease of the protozoan parasite Trypanosoma brucei and a therapeutic target for sleeping sickness, a fatal neglected tropical disease. We designed, synthesized and characterized a bimodal activity‐based probe that binds to and inactivates rhodesain. This probe exhibited an irreversible mode of action and extraordinary potency for the target protease with a kinac/Ki value of 37,000 M−1s−1. Two reporter tags, a fluorescent coumarin moiety and a biotin affinity label, were incorporated into the probe and enabled highly sensitive detection of rhodesain in a complex proteome by in‐gel fluorescence and on‐blot chemiluminescence. Furthermore, the probe was employed for microseparation and quantification of rhodesain and for inhibitor screening using a competition assay. The developed bimodal rhodesain probe represents a new proteomic tool for studying Trypanosoma pathobiochemistry and antitrypanosomal drug discovery.
Cardiac events among patients with sarcoma treated with doxorubicin by method of infusion: A real‐world database study
Authors: Cranmer Lee D. , Hess Lisa M. , Sugihara Tomoko , Muntz Howard G.
Published: July 2022

Background

Administration of doxorubicin by continuous intravenous (CIV) infusion, versus bolus (BOL) administration, has been proposed to mitigate the risk of cardiac events. This study used real‐world data to explore the association between mode of doxorubicin administration and duration of treatment, time‐to‐treatment failure (TTF), and cardiac events.

Methods

Occurrence of cardiac events after initiation of BOL versus CIV doxorubicin for sarcoma in the International Business Machines MarketScan claims database were compared. Duration of doxorubicin treatment, TTF, and time‐to‐first‐cardiac event (TCE) were evaluated using Kaplan–Meier method and unadjusted and adjusted Cox regression models.

Results

A total of 196 patients were included in the BOL group and 399 in the CIV group. In unadjusted analyses, there were significant differences between BOL versus CIV for duration of doxorubicin treatment (median 1.4 vs. 2.1 months, p = .002), TTF (median 8.8 vs. 5.6 months, p = .002), and TCE (medians not reached, p = .03). Adjusting for baseline covariates, only TTF remained significant (hazard ratio: 0.71, 95% confidence interval 0.59–0.86, p = .0004), favoring BOL.

Conclusions

While the risk of cardiac complications was higher with BOL in unadjusted analysis, the risk was no longer present in the adjusted analysis. While we cannot draw causal inferences due to the retrospective, nonrandomized study design, these data suggest that replacing BOL with prolonged CIV administration has not been effective as a strategy to mitigate cardiac events, given community standards of oncologic practice.
Visualization of profiling and tracing in CPU‐GPU programs
Authors: Fiorini Arnaud , Dagenais Michel R.
Published: July 2022

As the complexity of the toolchain increases for heterogeneous CPU‐GPU systems, the needs for comprehensive tracing and debugging tools also grows. Heterogeneous platforms bring new possibilities but also new performance issues that are hard to detect. Some techniques that were used on CPU programs are now adapted to GPUs. However, there are some concepts specific to GPUs, like SIMD processing, and the effects of the close interactions between the CPUs and the GPUs, with shared virtual memory and user‐level queues. Multiple sources of data need to be extracted and correlated to obtain a more global view of the performance. In this article, we introduce a novel approach for measuring and visualizing performance defects inside CPU‐GPU programs by combining kernel events, compute kernel events, user API calls and memory transfers. We created two new views that combine this information, to help provide a global view. This framework uses the open source user queue system described in the HSA standard. It can easily be adapted to any user queue system for heterogeneous computing devices. We compare this framework with current existing tools and test it against the Rodinia benchmark. We look at how the execution behavior affects the tracing and profiling overhead and we use Trace Compass to visualize the resulting trace.
Science gateway adoption using plug‐in middleware for evidence‐based healthcare data management
Authors: Oruche Roland , Milman Eric , Lemus Alarcon Mauro , Cheng Xiyao , Pandey Ashish , Wang Songjie , Calyam Prasad , Kee Kerk
Published: July 2022

There is a growing need for next‐generation science gateways to increase the accessibility of emerging large‐scale datasets for data consumers (e.g., clinicians, researchers) who aim to combat COVID‐19‐related challenges. Such science gateways that enable access to distributed computing resources for large‐scale data management need to be made more programmable, extensible, and scalable. In this article, we propose a novel socio‐technical approach for developing a next‐generation healthcare science gateway, namely,OnTimeEvidencethat addresses data consumer challenges surrounding the COVID‐19 pandemic related data analytics. OnTimeEvidence implements an intelligent agent, namely,Vidura Advisorthat integrates an evidence‐based filtering method to transform manual practices and improve scalability of data analytics. It also features a plug‐in management middleware that improves the programmability and extensibility of the science gateway capabilities using microservices. Lastly, we present a usability study that shows the important factors from data consumers' perspective to adopt OnTimeEvidence with chatbot‐assisted middleware support to increase their productivity and collaborations to access vast publication archives for rapid knowledge discovery tasks.
Comparison of Nitrogen Activation on Trinuclear Niobium and Tungsten Sulfide Clusters Nb3Sn and W3Sn (n=0–3): A DFT Study
Authors: Gurti Joseph Israel , Ding Xun‐Lei , Wang Ya−Ya , Chen Yan , Li Wei , Wang Xin
Published: July 2022

The front cover artwork is provided by Prof. Xun‐Lei Ding's group at North China Electric Power University (NCEPU). The image shows the cleavage of the triple bond of a dinitrogen molecule on trinuclear metal clusters with sulfide ligands, which is the critical step in nitrogen reduction reactions (NRR). Read the full text of the Research Article at 10.1002/cphc.202200124.
Synthesis and Photochemical Investigation of Tetraacylgermanes
Authors: Haslinger Carola , Leutgeb Lukas P. , Haas Michael , Baudis Stefan , Liska Robert
Published: July 2022

Tetraacylgermanes are auspicious candidates for additive manufacturing (such as lithography based ceramic manufacturing), as they are known to show high reactivity towards (meth)acrylates and absorption at wavelengths above 460 nm. We synthesized two novel tetraacylgermanes and investigated the reactivity of these compounds with methoxy groups in the ortho position of the aromatic moiety by comparing them both to reference substances lacking this substitution pattern and to the commercial benchmark Ivocerin®. In order to rationally assess the performance of these photoinitiators, steady‐state photolysis (SSP) experiments and RT‐FTIR photorheology measurements were performed. Comparable strong absorption in the long wavelength region and high photoreactivity has been found for the new initiators.
Metabolic study of hypoxia‐inducible factor stabilizers BAY 87‐2243, MK‐8617, and PT‐2385 in equine liver microsomes for doping control
Authors: Philip Moses , Karakka Kal Abdul Khader , Mathew Binoy , Subhahar Michael Benedict , Karatt Tajudheen K. , Perwad Zubair
Published: July 2022

A number of erythropoiesis stimulants are entering the final stage of clinical trials due to recent scientific progress in hypoxia‐regulated erythropoiesis. Considering how erythropoiesis‐stimulating compounds enhance the capacity of the organism to transport oxygen, they pose a great risk of being misused as performance enhancers. In this paper, we report the metabolic fate of three popular hypoxia‐inducible factor‐prolyl hydroxylase Inhibitors (HIF‐PHI) compounds, namely, BAY 87‐2243, MK‐8617, and PT‐2385 in equine liver microsomes using Q‐Exactive high‐resolution mass spectrometry. This study found 22 metabolites for BAY 87‐2243 (19 phase I and three phase II), three metabolites for MK‐8617 (all phase I), and five metabolites for PT‐2385 (two phase I and three phase II). The major findings of the present study are as follows: (1) all three potential HIF‐PHI drug candidates, namely, BAY 87‐2243, MK‐8617, and PT‐2385 are susceptible to oxidation, producing their corresponding hydroxylated metabolites; (2) the ring dissociated metabolites were detected for BAY 87‐2243 and PT‐2385; (3) in the case of BAY 87‐2243 and PT‐2385, glucuronic acid conjugated metabolites were detected; and (4) none of the drugs produced sulfonic acid conjugated metabolites.
Feasibility and acceptability of video‐based microinterventions for eating disorder prevention among adolescents in secondary schools
Authors: Kristoffersen Mhairi , Johnson Catherine , Atkinson Melissa J.
Published: July 2022

Objective

Eating disorders (EDs) often emerge in late adolescence. Schools are ideal settings for prevention programs; however, cost and time limit implementation. Microinterventions may overcome these challenges. This study adapted two microinterventions (cognitive dissonance, self‐compassion) and assessed feasibility and acceptability among mid‐adolescents to provide proof‐of‐concept for further investigation.

Method

Feedback from staff (n = 5) and student (n = 15) focus groups contributed iteratively to the adaptation of intervention materials. Students in Grade 10 and 11 (N = 101, Mage = 15.80, SD = 0.68) were then randomly allocated by class to a 20‐min video‐based cognitive‐dissonance or self‐compassion intervention, accessed on their school devices. ED risk and protective factors were assessed at baseline, immediate postintervention (state outcomes), and 1‐week follow‐up (trait outcomes). Acceptability items were included at both timepoints.

Results

Implementation was deemed feasible. Girls generally reported greater acceptability than boys. Among girls, the self‐compassion intervention demonstrated greater acceptability. Among boys, some aspects of acceptability (e.g., lesson endorsement, utilization of techniques) were rated higher in the cognitive dissonance group whereas other aspects (e.g., understanding, interest) were greater in the self‐compassion group. All groups exhibited favorable changes in most state outcomes, however trait outcome change was varied.

Discussion

Microinterventions provide a feasible way of implementing prevention strategies in a time‐poor educational context. Future large‐scale evaluation is warranted to determine efficacy, following modifications based on current findings.

Public Significance

This study shows promising feasibility and acceptability of two brief, self‐guided video‐based lessons (microinterventions) for adolescents in school classrooms, that use psychological techniques to target appearance pressures as a key risk factor for eating disorders. Such interventions are easier to implement in school settings than longer, facilitator‐led interventions, to encourage greater uptake and ongoing use. Findings support further research to evaluate effectiveness, to ultimately provide accessible and gender‐inclusive tools for busy schools.
The world's largest omnivore is a fish
Authors: Meekan M. G. , Virtue P. , Marcus L. , Clements K. D. , Nichols P. D. , Revill A. T.
Published: July 2022

The evolution of very large body size requires a ubiquitous and abundant source of food. In marine environments, the largest animals such as whale sharks are secondary consumers that filter feed on nekton, which is plentiful, although patchy. Consequently, feeding in coastal environments requires cost‐efficient foraging that focuses on oceanographic features that aggregate both nektonic prey and marine debris such as floating macroalgae. Consumption of this algae could present an energetic challenge for these animals, unless some component can be digested. Here, we use a multi‐technique approach involving amino acid compound‐specific stable isotope analysis (CSIA) and fatty acid analysis to determine the trophic level of whale sharks and to identify likely items in the diet. CSIA analyses showed that the species has a trophic level consistent with omnivory. Fatty acid profiles of whale shark tissues, feces and potential prey items suggest that the floating macroalgae, Sargassum, and its associated epibionts is a significant source of food. Although this overcomes the energetic challenge of consumption of floating algae, this mode of feeding and the need to focus on oceanographic features that aggregate prey also increases the threat to the species posed by pollutants such as plastic.
Clinical effect of obesity on N‐terminal pro‐B‐type natriuretic peptide cut‐off concentrations for the diagnosis of acute heart failure
Authors: Kozhuharov Nikola , Martin Jasmin , Wussler Desiree , Lopez‐Ayala Pedro , Belkin Maria , Strebel Ivo , Flores Dayana , Diebold Matthias , Shrestha Samyut , Nowak Albina , Gualandro Danielle M. , Michou Eleni , Zimmermann Tobias , Rentsch Katharina , von Eckardstein Arnold , Keller Dagmar I. , Breidthardt Tobias , Mueller Christian ,   BASEL V Investigators
Published: July 2022

Aims

Obese patients have lower natriuretic peptide concentrations. We hypothesized that adjusting the concentration of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) for obesity could further increase its clinical utility in the early diagnosis of acute heart failure (AHF).

Methods and results

This hypothesis was tested in a prospective diagnostic study enrolling unselected patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists/internists centrally adjudicated the final diagnosis using all individual patient information including cardiac imaging. NT‐proBNP plasma concentrations were applied: first, using currently recommended cut‐offs; second, using cut‐offs lowered by 33% with body mass index (BMI) of 30–34.9 kg/m2 and by 50% with BMI ≥ 35 kg/m2. Among 2038 patients, 509 (25%) were obese, of which 271 (53%) had AHF. The diagnostic accuracy of NT‐proBNP as quantified by the area under the receiver‐operating characteristic curve was lower in obese versus non‐obese patients (0.890 vs. 0.938). For rapid AHF rule‐out in obese patients, the currently recommended cut‐off of 300 pg/ml achieved a sensitivity of 96.7% (95% confidence interval [CI] 93.8–98.2%), ruling out 29% of patients and missing 9 AHF patients. For rapid AHF rule‐in, the age‐dependent cut‐off concentrations (age <50 years: 450 pg/ml; age 50–75 years: 900 pg/ml; age >75 years: 1800 pg/ml) achieved a specificity of 84.9% (95% CI 79.8–88.9%). Proportionally lowering the currently recommended cut‐offs by BMI increased sensitivity to 98.2% (95% CI 95.8–99.2%), missing 5 AHF patients; reduced the proportion of AHF patients remaining in the ‘gray zone’ (48% vs. 26%; p = 0.002), achieving a specificity of 76.5% (95% CI 70.7–81.4%).

Conclusions

Adjusting NT‐proBNP concentrations for obesity seems to further increase its clinical utility in the early diagnosis of AHF.
Use of guideline‐recommended medical therapy in patients with heart failure and chronic kidney disease: from physician's prescriptions to patient's dispensations, medication adherence and persistence
Authors: Janse Roemer J. , Fu Edouard L. , Dahlström Ulf , Benson Lina , Lindholm Bengt , van Diepen Merel , Dekker Friedo W. , Lund Lars H. , Carrero Juan‐Jesus , Savarese Gianluigi
Published: July 2022

Aim

Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians' and patients' patterns of use of evidence‐based medical therapies in HF across CKD stages.

Methods and results

We studied HF patients with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction enrolled in the Swedish Heart Failure Registry in 2009–2018. We investigated the likelihood of physicians to prescribe guideline‐recommended therapies to patients with CKD, and of patients to fill the prescriptions within 90 days of incident HF (initiating therapy), to adhere (proportion of days covered ≥80%) and persist (continued use) on these treatments during the first year of therapy. We identified 31 668 patients with HFrEF (median age 74 years, 46% CKD). The proportions receiving a prescription for angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors (ACEi/ARB/ARNi) were 96%, 92%, 86%, and 68%, for estimated glomerular filtration rate (eGFR) ≥60, 45–59, 30–44, and <30 ml/min/1.73 m2, respectively; for beta‐blockers 94%, 93%, 92%, and 92%, for mineralocorticoid receptor antagonists (MRAs) 45%, 44%, 37%, 24%; and for triple therapy (combination of ACEi/ARB/ARNi + beta‐blockers + MRA) 38%, 35%, 28%, and 15%. Patients with CKD were less likely to initiate these medications, and less likely to adhere to and persist on ACEi/ARB/ARNi, MRA, and triple therapy. Among stoppers, CKD patients were less likely to restart these medications. Results were consistent after multivariable adjustment and in patients with HFmrEF (n = 15 114).

Conclusions

Patients with HF and CKD are less likely to be prescribed and to fill prescriptions for evidence‐based therapies, showing lower adherence and persistence, even at eGFR categories where these therapies are recommended and have shown efficacy in clinical trials.
Research on the feasibility of polyethylene terephthalate foam used in wind turbine blades
Authors: Liu Haiming , Antwi‐Afari Maxwell Fordjour , Mi Haoyang , Liu Chuntai
Published: July 2022

The sandwich foam materials of wind turbine blades are mainly polyvinyl chloride (PVC) and styrene–acrylonitrile (SAN) foams due to their good mechanical properties. However, PVC foam is unrecyclable and not resistant to high‐temperature conditions, while SAN foam is more expensive than PVC foam. Polyethylene terephthalate (PET) has irreplaceable advantages than both PVC and SAN foams because of its better mechanical performance, fantastic heat‐resistant, low cost, and environmental friendliness (100% recyclability). In this article, the mechanical properties, thermal stability, resin uptake, and cellular morphology of PET T92, PVC H60, and SAN T400 foams were discussed. The results showed that the mechanical properties of T92 were equivalent to the existing H60 and T400, and even exceed their properties. It was found that the thermal stability of T92 was better than H60 and T400 under the same high temperature. Moreover, the pore of T92 was more uniform and regular than H60 and T400. Furthermore, the overall cost of T92 was lower than H60 and T400. The findings suggest that PET foam with a density of 100 kg/m3 can completely replace PVC 60 kg/m3 and SAN 71 kg/m3 foams from the perspective of mechanical performance, cost, thermal stability, and environmental protection.
Prioritizing Pharmaceutical Contaminants in Great Lakes Tributaries Using Risk-Based Screening Techniques
Authors: Pronschinske Matthew A. , Corsi Steven R. , DeCicco Laura A. , Furlong Edward T. , Ankley Gerald T. , Blackwell Brett R. , Villeneuve Daniel L. , Lenaker Peter L. , Nott Michelle A.
Published: July 2022

In a study of 44 diverse sampling sites across 16 Great Lakes tributaries, 110 pharmaceuticals were detected of 257 monitored. The present study evaluated the ecological relevance of detected chemicals and identified heavily impacted areas to help inform resource managers and guide future investigations. Ten pharmaceuticals (caffeine, nicotine, albuterol, sulfamethoxazole, venlafaxine, acetaminophen, carbamazepine, gemfibrozil, metoprolol, and thiabendazole) were distinguished as having the greatest potential for biological effects based on comparison to screening-level benchmarks derived using information from two biological effects databases, the ECOTOX Knowledgebase and the ToxCast database. Available evidence did not suggest substantial concern for 75% of the monitored pharmaceuticals, including 147 undetected pharmaceuticals and 49 pharmaceuticals with screening-level alternative benchmarks. However, because of a lack of biological effects information, screening values were not available for 51 detected pharmaceuticals. Samples containing the greatest pharmaceutical concentrations and having the highest detection frequencies were from Lake Erie, southern Lake Michigan, and Lake Huron tributaries. Samples collected during low-flow periods had higher pharmaceutical concentrations than those collected during increased-flow periods. The wastewater-treatment plant effluent content in streams correlated positively with pharmaceutical concentrations. However, deviation from this correlation demonstrated that secondary factors, such as multiple pharmaceutical sources, were likely present at some sites. Further research could investigate high-priority pharmaceuticals as well as those for which alternative benchmarks could not be developed. Environ Toxicol Chem 2022;41:2221–2239. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Joint optimization algorithm of user association and power control based on spatial traffic distribution
Authors: Wang Weipeng , Zhao Jihong , Qu Hua , Zhang Yanpeng , Ren Gongye
Published: July 2022

5G networks must reduce network overhead while meeting user needs. Based on the flow model, this paper jointly optimizes the user association and power control in cellular networks, aiming at achieving a reasonable compromise between user delay and network energy consumption. Unlike previous snapshot models, flow models focus on the spatial distribution of traffic demand instead of the specific location of users. We consider a nonuniformity of spatial traffic distribution and load coupling among base stations (BSs). Firstly, an iterative algorithm is proposed to solve the optimal user association strategy under certain power of BSs. Then, a greedy power adjustment and user association algorithm (GPA‐UA) is proposed to further optimize the objective function. The simulation results show that the proposed algorithm can reduce both user delay and network energy consumption in most cases, and the performance of the proposed algorithm is approximate to the Optimal scheme while GPA‐UA has lower complexity.
Determination of the lactose and galactose content of common foods: Relevance to galactosemia
Authors: Shakerdi Loai A. , Wallace Leonie , Smyth Georgina , Madden Nora , Clark Anne , Hendroff Una , McGovern Marianne , Connellan Sarah , Gillman Barbara , Treacy Eileen P.
Published: July 2022

Classical galactosemia (CG) is a disorder of galactose metabolism which results from deficiency of the enzyme galactose‐1‐phosphate uridylyl transferase (GALT). Treatment consists of immediately eliminating galactose from the diet in the new‐born and lifelong restriction of dietary galactose. The inclusion of a wider variety of foods for people with CG may provide many benefits, including improved nutritional adequacy and quality of life. Galactose plays an important role in glycosylation of glycoproteins and glycolipids. Moderate liberalization of galactose restriction has been shown to improve immunoglobulin G (IgG) glycosylation for some individuals with CG. Moreover, recent outcome research suggests that strict restriction of nondairy galactose may have more unfavorable outcomes than moderate liberalization in CG patients. In the current work, based on patient feedback, we have analyzed the lactose and galactose content of different foods available in Ireland. These include a range of cheeses, yogurts, pizzas, soups, biscuits, cakes, pastries, crackers, mayonnaises, salad creams, fat spreads, crisps, corn chips, salamis, and gravies. This work provides information to support the development of a practical food‐based approach to facilitate analysis of dietary galactose intake and to possibly increase overall variety of food choices for people with CG.
Stable isotope geochemistry and microfossil assemblages of carbonate rocks in the ophiolite mélange zone of the Indo–Myanmar orogenic Belt, NE India: Implications on age and depositional environment
Authors: Singh Athokpam Krishnakanta , Guruaribam Venus , Singh Yengkhom Raghumani , Singh Nongmaithem Ibotombi , Singh Leimapokpam Romendro , Chaubey Monika , Tewari Vinod Chandra , Singh Wangkheimayum Inaocha , Lakhan Nongmaithem , Devi Loitongbam Debala , Chanu Rajkumari Sanalembi
Published: July 2022

A comprehensive data of whole‐rock and stable isotopic geochemistry along with microfossil assemblages of the carbonate rocks of the ophiolite mélange zone of the Indo–Myanmar orogenic Belt (IMOB), north‐east India are discussed, to determine the influence of terrigenous contamination during the formation of these carbonate rocks and also to understand their depositional environment and ages. These carbonate rocks contain a diverse fauna with the dominance of foraminiferal assemblages of planktonic foraminifera (Globotruncana sp. and Heterohelix sp., etc.) which indicates they were formed during the Santonian to Maastrichtian age. Based on chemical compositions, these carbonate rocks have been identified as limestone (CaO/MgO > 50.1) to slightly dolomitic limestone (9.1 < CaO/MgO < 50.1). Total rare earth element (REE) contents in these carbonates are variable (22.39–146.05 ppm). The Post‐Archean Australian Shale (PAAS)‐normalized REE + Y patterns of these carbonates exhibit seawater‐like REE patterns with LREE depletion and relative HREE enrichment with negative Ce anomalies (Ce/Ce* = 0.32–0.79) and positive Y (4.42–27.81 ppm) and Eu anomalies (Eu/Eu* = 1.11–1.86), suggesting that they were deposited under an oxygenated environment with contamination by hydrothermal activity. They are also depleted in δ13C 0/00 (PDB) (1.02–1.570/00) and δ18O 0/00 (PDB) (−6.37 to −9.00%) values which characterize marine precipitates. Eu anomalies and spread in negative δ18O 0/00 (PDB) values to a lesser extent of δ13C 0/00 (PDB) values of these carbonates suggest their formation was altered by diagenesis in the shallow marine environment. Our new whole‐rock and stable isotope geochemical characteristics, in conjunction with microfacies, suggest that the investigated carbonate rocks might have been formed in low‐energy environments, and deposited in neritic to bathyal palaeoenvironments during the Santonian to Maastrichtian interval.
A hierarchical anatomical framework and workflow for organizing stereotactic encephalography in epilepsy
Authors: Zheng Bryan , Hsieh Ben , Rex Nathaniel , Lauro Peter M. , Collins Scott A. , Blum Andrew S. , Roth Julie L. , Ayub Neishay , Asaad Wael F.
Published: July 2022

Stereotactic electroencephalography (SEEG) is an increasingly utilized method for invasive monitoring in patients with medically intractable epilepsy. Yet, the lack of standardization for labeling electrodes hinders communication among clinicians. A rational clustering of contacts based on anatomy rather than arbitrary physical leads may help clinical neurophysiologists interpret seizure networks. We identified SEEG electrodes on post‐implant CTs and registered them to preoperative MRIs segmented according to an anatomical atlas. Individual contacts were automatically assigned to anatomical areas independent of lead. These contacts were then organized using a hierarchical anatomical schema for display and interpretation. Bipolar‐referenced signal cross‐correlations were used to compare the similarity of grouped signals within a conventional montage versus this anatomical montage. As a result, we developed a hierarchical organization for SEEG contacts using well‐accepted, free software that is based solely on their post‐implant anatomical location. When applied to three example SEEG cases for epilepsy, clusters of contacts that were anatomically related collapsed into standardized groups. Qualitatively, seizure events organized using this framework were better visually clustered compared to conventional schemes. Quantitatively, signals grouped by anatomical region were more similar to each other than electrode‐based groups as measured by Pearson correlation. Further, we uploaded visualizations of SEEG reconstructions into the electronic medical record, rendering them durably useful given the interpretable electrode labels. In conclusion, we demonstrate a standardized, anatomically grounded approach to the organization of SEEG neuroimaging and electrophysiology data that may enable improved communication among and across surgical epilepsy teams and promote a clearer view of individual seizure networks.
MeCP2 loss‐of‐function dysregulates microRNAs regionally and disrupts excitatory/inhibitory synaptic transmission balance
Authors: Horvath Patricia M. , Piazza Michelle K. , Kavalali Ege T. , Monteggia Lisa M.
Published: July 2022

Rett syndrome is a leading cause of intellectual disability in females primarily caused by loss of function mutations in the transcriptional regulator MeCP2. Loss of MeCP2 leads to a host of synaptic phenotypes that are believed to underlie Rett syndrome pathophysiology. Synaptic deficits vary by brain region upon MeCP2 loss, suggesting distinct molecular alterations leading to disparate synaptic outcomes. In this study, we examined the contribution of MeCP2's newly described role in miRNA regulation to regional molecular and synaptic impairments. Two miRNAs, miR‐101a and miR‐203, were identified and confirmed as upregulated in MeCP2 KO mice in the hippocampus and cortex, respectively. miR‐101a overexpression in hippocampal cultures led to opposing effects at excitatory and inhibitory synapses and in spontaneous and evoked neurotransmission, revealing the potential for a single miRNA to broadly regulate synapse function in the hippocampus. These results highlight the importance of regional alterations in miRNA expression and the specific impact on synaptic function with potential implications for Rett syndrome.
Laser‐enabled delivery of antiretroviral drugs into HIV‐1 infected TZM‐bl cells
Authors: Maphanga Charles , Manoto Sello , Mabena Chemist , Ombinda‐Lemboumba Saturnin , Maaza Malik , Mthunzi‐Kufa Patience
Published: July 2022

The use of femtosecond laser to create sub‐microscopic transient pores on the cell membrane allowing exogenous material into mammalian cells has become a very efficient optical delivery method over the past decade. This study focuses on laser‐enabled delivery of antiretroviral (ARV) drugs into HIV‐1 infected TZM‐bl cells in vitro. A 1 kHz femtosecond laser emitting at a wavelength of 800 nm was used to photoporate cells at 6.5 μW. Trypan blue was used for characterisation and its uptake was quantified using Matlab software. Cell membrane damage was assessed using the lactate dehydrogenase (LDH) assay while HIV‐1 infection was assessed using luciferase assay. Our results showed successful delivery of ARVs into HIV‐1 infected cells without compromising their cell membranes, subsequently reducing the level of infection. The LDH assay showed no significant cell membrane damage of laser‐treated cells, and the luciferase assay demonstrated significant reduction in the level of HIV‐1 infection.
A high spatial resolution osteogenic differentiation in human mesenchymal stem cells induced by femtosecond laser
Authors: Liu Shiyue , Chen Dihan , Xie Zhenming , Zhao Shirui , Tang Wanyi , He Hao , Ho Yi‐Ping , Ho Ho‐Pui , Kong Siu‐Kai
Published: July 2022

A variety of physical and chemical methods have been developed in research laboratories for the induction of stem cell differentiation. However, the use of exogenous chemicals and materials may limit their widespread utility in clinics. To develop a clean and precise induction approach with minimal invasion, we reported here that 1‐second stimulation by a tightly focused femtosecond laser (fsL) (140 mW/μm2, 200 fs) can modulate the signaling systems in human mesenchymal cells, such as intracellular calcium and reactive oxygen species. Upon stimulation on an automatic platform, hMSCs were found to express osteoblastic markers and form calcium‐rich deposits. Moreover, tissue mineralization was observed when the fsL‐illuminated hMSCs were ectopically transplanted into nude mice. Collectively, we described a novel and non‐contact optical stimulation method for cell differentiation with high spatiotemporal resolution.
Preparation and characterization of Schiff base nickel complexes and their application in the coupling reaction of cyclohexene oxide and carbon dioxide
Authors: Hsu Shih‐Hsien , Chen Hung‐Chih , Hung Yu‐Ching , Li Yi‐Xuan , Liu Guan‐Lin , Ko Bao‐Tsan , Lin Chu‐Chieh
Published: July 2022

A series of novel nickel complex (1–10) supported by NNO‐tridentate Schiff‐base ligands (L1H–L10H) were synthesized and used as catalysts for the reaction of cyclohexene oxide (CHO) and carbon dioxide. Structure determination reveals that all of these complexes are di‐nuclear species with either hexa‐coordinated Ni centers [(OAc)Ni(μ‐L)2(μ‐H2O)Ni(OAc)] (1–6, 9–10) or penta‐coordinated Ni centers [(LNi(μ‐OAc)2NiL] (7–8) with respect to various electronic and steric effect. Interestingly, experimental results indicated that these complexes were inactive in the reaction of CO2 and CHO in the absence of co‐catalysts. However, they exhibited efficient activity and high selectivity yielding cyclic carbonate in the presence of ammonium halides. Among them, complexes with more steric bulky ligand showed somewhat higher activity. Kinetic studies reveal the reaction of CHO and CO2 catalyzed by 4 in the presence of 4 equiv of nBu4NCl as co‐catalyst yielding cyclic carbonate with active energy (ΔG‡) of 59.1 kJ/mol, ΔH‡ of 55.86 kJ/mol and ΔS‡ of −118.28 J/(mol × K) indicating association of substrates occurs prior to the rate‐determining step.
Reference intervals of anti‐Müllerian hormone in Korean women
Authors: Choi Rihwa , Lee Sang Gon , Lee Eun Hee
Published: July 2022

Background

Limited data are available with reference intervals of serum anti‐Müllerian hormone (AMH) level in Korean women.

Methods

We retrospectively reviewed serum AMH test results performed with automated electrochemiluminescence immunoassay in Korean women who visited health promotion centers between January 2019 and December 2020. Serum AMH results by age group were compared with previously reported reference intervals.

Results

During the 2‐year study period, a total of 1953 AMH test results from Korean women (age 20–49 years) undergoing general health checkups were obtained. Serum AMH level differed significantly by age group. Peak AMH level was observed at age 25–29 years and decreased to undetectable for subjects older than 44 years. The 2.5th, 5th, and 10th percentile values of the present study were comparable with previously assessed lower limits of reference intervals. The upper limit of the reference interval defined as the 97.5th percentile value in women younger than 35 years was higher than that of Western populations. The 90th percentile value of the present study population was similar to the 95th or 97.5th percentile value of reference intervals for Western populations of women younger than 35 years.

Conclusion

Understanding patient populations and differences in reference intervals by age group and measurement method can help guide clinical decisions and clinical laboratory analysis.
An insight into the diagnostic and prognostic value of HOX A13’s expression in non‐muscle invasive bladder cancer
Authors: Setti Boubaker Nouha , Gurtner Aymone , Trabelsi Nesrine , Manni Isabella , Blel Ahlem , Saadi Ahmed , Chakroun Marouene , Naimi Zeineb , Zaghbib Selim , Ksontini Meriam , Meddeb Khedija , Rammeh Soumaya , Ayed Haroun , Chebil Mohamed , Piaggio Giulia , Ouerhani Slah
Published: July 2022

Background

Several studies have interrogated the molecular pathways and their interacting genes underlying bladder cancer (BCa) tumorigenesis, yet, the role of homeobox genes is still poorly understood. Specifically, HOXA13, which plays an important role as a major actor in the urogenital tract's development.

Methods

Immunohistochemical (IHC) staining was performed to inspect the differential expression of HOXA13 protein in non‐muscle‐invasive bladder cancer (NMIBC) and non‐tumoral tissues. A semiquantitative scoring system was adopted to evaluate the IHC labeling. Correlation to clinical parameters was performed by descriptive statistics. Overall survival was estimated by the Kaplan–Meier method and Cox regression model. The functional HOX A13 protein association networks (PPI) were obtained using String 11.0 database.

Results

HOX A13 exhibited cytoplasmic and nuclear staining. Its expression levels were lower in high‐grade NMIBC (HG NMIBC) compared to low‐grade ones (LG NMIBC). The expression of HOX A13 was correlated to tumor grade (LG/HG) (p = 0.036) and stage (TA/T1) (p = 0.036). Nevertheless, its expression was not correlated to clinical parameters and was not able to predict the overall survival of patients with HG NMIBC. Finally, PPI analysis revealed that HOX A13 seems to be a part of a molecular network holding mainly PBX1, MEIS, ALDH1A2, HOX A10, and HOX A11.

Conclusion

The deregulation of HOX A13 is not associated with the prognosis of BCa. It seems to be rather implicated in the early initiation of urothelial tumorigenesis and thus may serve as a diagnostic marker in patients with NMIBC. Further experimentations on larger validation sets are mandatory.
Pleiotropic roles of evolutionarily conserved signaling intermediate in toll pathway (ECSIT) in pathophysiology
Authors: Chaitanya Nyshadham S. N. , Tammineni Prasad , Nagaraju Ganji Purnachandra , Reddy Aramati BM
Published: July 2022

The evolutionarily conserved signaling intermediate in toll pathway (ECSIT) is a cytosolic adaptor protein associated with the toll‐like receptor pathway. It has a distinct N‐terminal mitochondrial targeting sequence, pentatricopeptide repeat motif, and a C‐terminal pleckstrin homology domain. ECSIT regulates many biological processes like embryonic development, inflammation, cardiac function, and assembly of mitochondrial complex I. Besides, ECSIT also interacts with multiple signaling intermediates like tumor necrosis receptor associated factor 6 and retinoic acid inducible gene 1 as well as regulates various pathways in the microcellular environment. However, molecular details of ECSIT functions in pathophysiology remain elusive. This review summarizes the diverse functions of ECSIT and its involvement in pathophysiological conditions such as Alzheimer's, oxidative stress, and infection.
Electric field enhanced heterogeneous Fenton reaction: simultaneous pollutant degradation and catalyst reactivation
Authors: Zhou Zijie , Yin Xu , Li Wei , Liu Run , Wei Kajia , Liu Xiaodong , Sun Xiuyun , Han Weiqing
Published: July 2022

BACKGROUND

Traditional Fe‐based heterogeneous Fenton catalysts have the problem of a low generation rate of Fe(II) from Fe(III), and this leads to poor reaction efficiency and catalyst deactivation. In this work, Fe3O4@N‐MWCNT catalyst with both strong magnetism and high electrical conductivity was synthesized. In addition, a novel unibody degradation‐reactivation reactor was designed for simultaneous pollutant degradation and catalyst reactivation.

RESULTS

The X‐ray Diffraction (XRD) patterns and Scanning Electron Microscope (SEM) images reveal the great dispersity of Fe3O4 loaded on oxidized‐MWCNT. The Vibrating Sample Magnetometer (VSM) tests and electrochemical characterization confirmed the strong magnetism, high electrical conductivity, and good capacitance performance of the catalyst. The optimum condition of heterogeneous Fenton degradation experiments was investigated. A favorable recovery of Fe(II) was confirmed through the detection of the Fe(II): Fe(III) ratio from X‐ray Photoelectron Spectroscopy (XPS) characterization.

CONCLUSION

The combination of Fe3O4 and MWCNT can significantly increase the heterogeneous Fenton catalytic activity of the catalyst. Under the assistance of a finely controlled flow pattern and an applied magnetic field, three different processes (including heterogeneous Fenton reaction, electrochemical oxidation, and catalyst reactivation) were joined organically into a synergistic reaction system. It is demonstrated that the catalyst can replenish the sacrificed electrons during the reactivation process and improve its cycling performance. © 2022 Society of Chemical Industry (SCI).
Local Patterns in 2‐Year T1ρ and T2 Changes of Hip Cartilage Are Related to Sex and Functional Data: A Prospective Evaluation on Hip Osteoarthritis Participants
Authors: Roach Koren E. , Souza Richard B. , Majumdar Sharmila , Pedoia Valentina
Published: July 2022

Background

Although T1ρ and T2 have emerged as early indicators for hip osteoarthritis (OA), there is little information regarding longitudinal changes across the cartilage in the early stages of this disease.

Purpose

To characterize the variability in 2‐year hip cartilage T1ρ and T2 changes and investigate associations between these patterns of change and common indicators of hip OA.

Study Type

Prospective.

Population

A total of 25 women (age: 51.9 ± 16.3 years old; BMI: 22.6 ± 2.0 kg/m2) and 17 men (age: 55.8 ± 14.9 years old; body mass index (BMI): 24.4 ± 3.8 kg/m2) who were healthy or with early‐to‐moderate hip OA.

Field Strength/Sequence

A 3 T MRI (GE), 3D combined T1ρ/T2 magnetization‐prepared angle‐modulated partitioned k‐space spoiled gradient echo snapshots.

Assessment

Principal component (PC) analysis of Z‐score difference maps of 2‐year changes in hip cartilage T1ρ and T2 relaxation times, participant hip disability and osteoarthritis outcome scores (HOOS) and functional tests at 2‐year follow‐up.

Statistical Tests

Shapiro–Wilk test, unpaired t‐tests, Kruskal Wallis tests, Pearson or Spearman (ρ) correlations. Significance was set at P < 0.05.

Results

Women (−6.40 ± 14.48) had significantly lower T1ρ PC1 scores than men (10.05 ± 26.15). T1ρ PC4 was significantly correlated with HOOSsport, HOOSsymptoms, HOOSpain, HOOSadl, and HOOSqol at 2‐year follow‐up (ρ: [0.36, 0.50]). T1ρ PC2 and PC4 were significantly correlated with 30‐second chair test (ρ = −0.39 and ρ = 0.24, respectively) and side plank (ρ = −0.32 and ρ = 0.21). T1ρ and T2 PC2 were significantly correlated with 40 m walk test (ρ = 0.34 and ρ = 0.31) and 30‐second chair rise test (ρ = −0.39 and ρ = −0.32).

Data Conclusion

Men exhibited accelerated T1ρ increases across the femoral cartilage compared to women, suggesting sex should be considered when evaluating early hip OA. Participants with poorer HOOS and function exhibited greater T1ρ and T2 increases in superior and anterior femoral cartilage and greater T1ρ increases in the anterior femoral cartilage. These patterns of short‐term relaxometry increases could indicate hip OA progression.

Evidence Level

2

Technical Efficacy

Stage 3
A comparative study on electromagnetic quasistatic time‐domain field calculations
Authors: Henkel Marvin‐Lucas , Kasolis Fotios , Schöps Sebastian , Clemens Markus
Published: July 2022

Electromagnetic quasistatic field models, which take into consideration resistive, inductive, and capacitive effects, have been introduced for electrical engineering applications whose geometrical characteristics, combined with the operational frequencies, suggest negligible radiation phenomena. Here, a monolithic variant of a previously proposed two‐step electromagnetic quasistatic algorithm and a two‐step time‐domain Maxwell formulation are presented, together with relevant initial‐boundary value problems. In view of numerical experiments, the fields that are obtained with the two‐step electromagnetic quasistatic algorithm, its monolithic variant, and the two‐step time‐domain Maxwell formulation are compared and turn out to be in good agreement.
Comprehensive two‐dimensional gas chromatographic platforms comparison for exhaled breath metabolites analysis
Authors: Zanella Delphine , Henin Adèle , Mascrez Steven , Stefanuto Pierre‐Hugues , Franchina Flavio Antonio , Focant Jean‐François , Purcaro Giorgia
Published: July 2022

The high potential of exhaled breath for disease diagnosis has been highlighted in numerous studies. However, exhaled breath analysis is suffering from a lack of standardized sampling and analysis procedures, impacting the robustness of inter‐laboratory results, and thus hampering proper external validation. The aim of this work was to verify compliance and validate the performance of two different comprehensive two‐dimensional gas chromatography coupled to mass spectrometry platforms in different laboratories by monitoring probe metabolites in exhaled breath following the Peppermint Initiative guidelines. An initial assessment of the exhaled breath sampling conditions was performed, selecting the most suitable sampling bag material and volume. Then, a single sampling was performed using Tedlar bags, followed by the trapping of the volatile organic compounds into thermal desorption tubes for the subsequent analysis using two different analytical platforms. The thermal desorption tubes were first analyzed by a (cryogenically modulated) comprehensive two‐dimensional gas chromatography system coupled to high‐resolution time‐of‐flight mass spectrometry. The desorption was performed in split mode and the split part was recollected in the same tube and further analyzed by a different (flow modulated) comprehensive two‐dimensional gas chromatography system with a parallel detection, specifically using a quadrupole mass spectrometer and a vacuum ultraviolet detector. Both the comprehensive two‐dimensional gas chromatography platforms enabled the longitudinal tracking of the peppermint oil metabolites in exhaled breath. The increased sensitivity of comprehensive two‐dimensional gas chromatography enabled to successfully monitor over a 6.5 h period a total of 10 target compounds, namely α‐pinene, camphene, β‐pinene, limonene, cymene, eucalyptol, menthofuran, menthone, isomenthone, and neomenthol.
Study on the synergistic and attenuating mechanism of the combination of Epimedium and Ligustri lucidi fructus based on pharmacokinetics
Authors: Wang Jiaqi , Cao Yijia , Feng Xin , Li Tianyi , Bi Yuelin , Zhang Tonghua , Xu Haoran , Yu Gengyuan , Zhang Chenning , Sun Yikun
Published: July 2022

Epimedium has a wide range of clinical applications; however, there have been numerous reports of adverse reactions in recent years, which has resulted in it being changed from a widely recognized “nontoxic” to a “potentially toxic” traditional Chinese medicine. The combination of Epimedium and Ligustri lucidi fructus is commonly used in the clinic. The purpose of this study was to investigate the pharmacokinetic characteristics of Epimedium and Ligustri lucidi fructus to explore the possible synergism and reduction in toxicity. Based on liquid chromatography tandem mass spectrometry, a method was established for the determination of icariin, epimedin A, epimedin B, epimedin C, baohuoside Ⅰ, and specnuezhenide in biological samples and was successfully applied to study the pharmacokinetics of the drug pair. The results showed that the five flavonoids (specnuezhenide could not be detected) could be rapidly absorbed into the blood, and the second peak time in vivo was earlier after the combination, indicating that the metabolic pathway may be changed. In addition, combination with Ligustri lucidi fructus could significantly reduce the concentration of 5 flavonoids in vivo and increase their elimination rate, which may attenuate their virulence, thus providing a reference for the rational clinical use of Epimedium.