bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of spirocyclopiperazinium salt compound LXM‐15 on spinal nerve injury in rats
Authors: Wang Tian Yu , Liang Ying Ying , Liu Qin , Wang Ding , Sun Qi , Li Run Tao , Yang Hua , Jiang Yi Min , Ye Jia
Published: September 2023

Background

Currently available therapies for neuropathic pain show limited efficacy. This study aimed to investigate the anti‐nociceptive effect of the spirocyclopiperazinium salt compound LXM‐15 in spinal nerve ligation (SNL) rats and to explore the potential mechanisms.

Methods

Mechanical allodynia and thermal hyperalgesia tests were used to evaluate the effects of LXM‐15 in SNL rats. The expression of CaMKIIα, CREB, JAK2, STAT3, c‐fos and TNF‐α was detected by western blotting, ELISA or qRT‐PCR analysis. Receptor blocking test was performed to explore possible target.

Results

Administration of LXM‐15 (1, 0.5, 0.25 mg/kg, i.g.) dose‐dependently attenuated mechanical allodynia and thermal hyperalgesia in rats subjected to SNL (p < 0.01, p < 0.05), and the effects were completely blocked by peripheral α7 nicotinic or M4 muscarinic receptor antagonist (p > 0.05). LXM‐15 significantly decreased the overexpression of phosphorylated CaMKIIα, CREB, JAK2 and STAT3 proteins and the mRNA levels of TNF‐α and c‐fos (p < 0.01, p < 05). All of the effects could be blocked by α7 or M4 receptor antagonist. Furthermore, LXM‐15 reduced the protein expression of TNF‐α and c‐fos (p < 0.01, p < 0.05). No significant acute toxicity or abnormal hepatorenal function was observed.

Conclusions

This is the first study to report that LXM‐15 exerts significant anti‐nociceptive effect on SNL rats. This effect may occur by activating peripheral α7 nicotinic and M4 muscarinic receptors, further inhibiting the CaMKIIα/CREB and JAK2/STAT3 signalling pathways, and finally inhibiting the expression of TNF‐α and c‐fos.

Significance

Existing treatments for neuropathic pain show limited efficacy with severe adverse reactions. This paper is the first to report that LXM‐15, a new spirocyclopiperazinium salt compound, exerts a significant anti‐nociception in SNL rats without obvious toxicity. The underlying mechanisms include activating peripheral α7 nicotinic and M4 muscarinic receptors, then inhibiting the signalling pathways of CaMKIIα/CREB and JAK2/STAT3 and the expressions of TNF‐α and c‐fos. This study sheds new light on the development of novel analgesic drugs with fewer side effects.
Opportunities and challenges for sample preparation and enrichment in mass spectrometry for single‐cell metabolomics
Authors: Wevers Dirk , Ramautar Rawi , Clark Charlie , Hankemeier Thomas , Ali Ahmed
Published: September 2023

Single‐cell heterogeneity in metabolism, drug resistance and disease type poses the need for analytical techniques for single‐cell analysis. As the metabolome provides the closest view of the status quo in the cell, studying the metabolome at single‐cell resolution may unravel said heterogeneity. A challenge in single‐cell metabolome analysis is that metabolites cannot be amplified, so one needs to deal with picolitre volumes and a wide range of analyte concentrations. Due to high sensitivity and resolution, MS is preferred in single‐cell metabolomics. Large numbers of cells need to be analysed for proper statistics; this requires high‐throughput analysis, and hence automation of the analytical workflow. Significant advances in (micro)sampling methods, CE and ion mobility spectrometry have been made, some of which have been applied in high‐throughput analyses. Microfluidics has enabled an automation of cell picking and metabolite extraction; image recognition has enabled automated cell identification. Many techniques have been used for data analysis, varying from conventional techniques to novel combinations of advanced chemometric approaches. Steps have been set in making data more findable, accessible, interoperable and reusable, but significant opportunities for improvement remain. Herein, advances in single‐cell analysis workflows and data analysis are discussed, and recommendations are made based on the experimental goal.
Collateral damage: military invasions beget biological invasions
Authors: Santini Alberto , Maresi Giorgio , Richardson David M , Liebhold Andrew M
Published: September 2023

Biological invasions are frequently and closely associated with armed conflict. As a key element of human history, war involves the invasion of (often distant) enemy territories, during which time species can be translocated, intentionally or unintentionally. Large‐scale conflicts such as World War I and II, in which thousands of soldiers and supplies (including foodstuffs) were transported within and between continents, resulted in the spread of non‐native taxa. However, smaller scale military actions may also involve rapid movements of troops between geographical areas, potentially facilitating the accidental introduction of species into previously unoccupied areas. Furthermore, invasive pests have occasionally been used by armies as weapons to weaken and disrupt opposing forces or nations. The introduction of invasive species during war could be considered relatively minor collateral damage, but many biological invasions in conflict zones have long‐lasting effects. Regulation of military practices to minimize or prevent biological invasions through existing international conventions has so far been unsuccessful, necessitating the development of additional measures.
Prioritizing science efforts to inform decision making on public lands
Authors: Carter Sarah K , Haby Travis S , Meineke Jennifer K , Foster Alison C , McCall Laine E , Espy Leigh D , Gilbert Megan A , Herrick Jeffrey E , Prentice Karen L
Published: September 2023

Public land management agencies in the US are committed to using science‐informed decision making, but there has been little research on the types and topics of science that managers need most to inform their decisions. We used the National Environmental Policy Act to identify four types of science information needed for making decisions relevant to public lands: (1) data on resources of concern, (2) scientific studies relevant to potential effects of proposed actions, (3) methods for quantifying potential effects of proposed actions, and (4) effective mitigation measures. We then used this framework to analyze 70 Environmental Assessments completed by the Bureau of Land Management in Colorado. Commonly proposed actions were oil and gas development, livestock grazing, land transactions, and recreation. Commonly analyzed resources included terrestrial wildlife, protected birds, vegetation, and soils. Focusing research efforts on the intersection of these resources and actions, and on developing and evaluating the effectiveness of mitigation measures to protect these resources, could strengthen the science foundation for public lands decision making.
Forecasting volatility with investor pessimism index: Exploring the predictive power of search queries
Authors: Chu Xiaojun , Xu Li
Published: September 2023

This paper discusses whether investor sentiment contains useful information to predict volatility by constructing investor pessimism index based on Baidu, which is the largest search engine in China. We discover that the investor pessimism index is significantly negatively correlated with contemporaneous returns but predicts following days' returns reversals. Furthermore, the heterogeneous autoregressive model of realized volatility (HAR‐RV) with investor pessimism index performs better than other HAR‐RV‐type benchmark models. We perform a series of robustness tests, which include alternative construction of investor pessimism index, crisis subsample, alternative predictive model, alternative measures of volatility, and considering the role of institutional investor. Our results remain robust. Taken together, investor pessimism index constructed in this paper seem to be a suitable proxy to measure investor sentiment in China and can enhance the accuracy of volatility forecasting in the Chinese stock market.
Felsbauplanung mit dem geotechnischen Werkzeugkasten von morgen: Perspektiven der Entwicklung der dritten Generation des Eurocodes 2035
Authors: Harrison John P. , Burbaum Ulrich , Lamas Luis , Spross Johan , Stille Håkan
Published: September 2023

The current Eurocode revision process is sought to improve Eurocode 7 for application to rock engineering, while including only techniques and procedures that are in widespread customary use. The revision process has exposed much about the application of the Eurocodes to rock engineering, thereby offering hints as to what material should be included in the next revision – tentatively suggested for publication in 2035. Crucially, ideas have developed about how rock engineering practice may need to develop to embrace the principles on which the Eurocodes are based. In particular, aspects of determining the properties of rock masses, and design verification by observational methods, partial factors, numerical modelling, and prescriptive rules are all thought to require significant improvement or dramatic modification. This paper highlights challenges identified regarding the application of the Eurocodes to rock engineering, and which will need to be addressed in the future. Ideas are presented about how these challenges may be overcome, but these are given in the spirit of stimulating ongoing conversation within the rock mechanics and rock engineering community rather than presenting definite proposals.
Genesis of the Lamasu large skarn Cu deposit, northern Xinjiang: Constraints from garnet U–Pb dating, micro‐textural and geochemical analyses
Authors: Wang Xiao‐Tong , Liu Jun , Lai Chun‐Kit , He Jun‐Cheng , Sun Peng , Yang Yan
Published: September 2023

The Lamasu deposit is the first large copper (Cu) deposit with ~0.6 Mt Cu reserve in the Chinese Western Tianshan Orogen (NW China). The Cu orebodies are mainly hosted in the exoskarn of the Proterozoic Kusongmuqieke Group. Now, the metallogenic mechanism of newly discovered skarn Cu orebodies (0.5 Mt Cu) remains poorly constrained. In this study, we conducted LA‐ICP‐MS U–Pb isotope dating, EPMA and LA‐ICP‐MS geochemical analyses on different generations of garnet from Lamasu to elucidate the magmatic hydrothermal evolution and its timing. Garnets from the Lamasu exoskarn can be divided into three types: reddish‐brown coarse‐grained Grt‐I, light brown fine‐grained Grt‐II and yellowish‐green heterogranular Grt‐III, with U–Pb age of 389.1 ± 2.0 Ma, 387.1 ± 1.8 Ma and 387.0 ± 2.3 Ma, respectively. These dates represent the oldest Cu mineralization age in the Chinese Western Tianshan, coeval with the Middle Devonian subduction of the North Tianshan oceanic plate. Grt‐I to Grt‐III particles are mainly andradite with minor grossularite, and they have different REE compositions. The Grt‐I has total REE contents (∑REE) of 101.47 to 262.87 ppm, with steeply right‐inclining REE distribution patterns (LREE/HREE of 3.81 to 68.50) and positive Eu anomaly. The Grt‐II core has ∑REE of 163.49–249.52 ppm, LREE/HREE of 2.00–4.71, and negative Eu anomaly. The Grt‐II rim has ∑REE of 46.34–99.99 ppm, with LREE/HREE of 18.06–177.23, and positive Eu anomaly. The ∑REE of Grt‐III range from 31.71 to 219.02 ppm, with flat REE distribution pattern and positive Eu anomaly, and the LREE/HREE ranges from 2.16 to 9.07. These garnets have similar trace element compositions, featured by LILE‐depletions (e.g., Rb, Ba and Sr) and HFSE enrichments (e.g., Th, U, Nb and Ce). Micro‐texture and geochemical composition of garnets indicate that the Lamasu magmatic hydrothermal system could have changed from an open to a closed environment, and from infiltration metasomatism to diffusive metasomatism, which formed Grt‐I, Grt‐II and Grt‐III successively. These garnets generally formed in a relatively oxidized fluid environment, which inhibited early sulphide precipitation and favoured for Cu enrichment during the ore fluid evolution.
Identification of gastric cancer types based on hyperspectral imaging technology
Authors: Tian Chongxuan , Su Wenjing , Huang Sirui , Shao Bowen , Li Xueyi , Zhang Yuanbo , Wang Bingjie , Yu Xiaojing , Li Wei
Published: September 2023

Gastric cancer is becoming the second biggest cause of death from cancer. Treatment and prognosis of different types of gastric cancer vary greatly. However, the routine pathological examination is limited to the tissue level and is easily affected by subjective factors. In our study, we examined gastric mucosal samples from 50 normal tissue and 90 cancer tissues. Hyperspectral imaging technology was used to obtain spectral information. A two‐classification model for normal tissue and cancer tissue identification and a four‐classification model for cancer type identification are constructed based on the improved deep residual network (IDRN). The accuracy of the two‐classification model and four‐classification model are 0.947 and 0.965. Hyperspectral imaging technology was used to extract molecular information to realize real‐time diagnosis and accurate typing. The results show that hyperspectral imaging technique has good effect on diagnosis and type differentiation of gastric cancer, which is expected to be used in auxiliary diagnosis and treatment.
Cardiovascular human organ‐on‐a‐chip platform for disease modeling, drug development, and personalized therapy
Authors: Khanna Astha , Oropeza Beu P. , Huang Ngan F.
Published: September 2023

Cardiovascular organ‐on‐a‐chip (OoC) devices are composed of engineered or native functional tissues that are cultured under controlled microenvironments inside microchips. These systems employ microfabrication and tissue engineering techniques to recapitulate human physiology. This review focuses on human OoC systems to model cardiovascular diseases, to perform drug screening, and to advance personalized medicine. We also address the challenges in the generation of organ chips that can revolutionize the large‐scale application of these systems for drug development and personalized therapy.
Personal Growth Initiative and Mental Health: A Meta‐Analysis
Authors: Weigold Ingrid K. , Weigold Arne , Russell Elizabeth J. , Wolfe Ginelle L. , Prowell Jusiah L. , Martin‐Wagar Caitlin A.
Published: September 2023

Personal growth initiative (PGI) is an individual's active and intentional desire to grow in personally important areas. In the past 20 years, a body of literature has emerged examining PGI's relationship to mental health. We conducted the first meta‐analyses to synthesize this literature. Two meta‐analyses examined the relationship between PGI total scores and distress (k = 22) and wellness (k = 37). Both average effect sizes were significant. We also examined the potential impact of nine moderators. The type of outcome assessed was a significant moderator for PGI and distress, and the PGI measure used was a significant moderator for PGI and wellness, accounting for 61% and 15% of the overall variance, respectively. Meta‐analyses examining the relationship between the four PGI subscales (Readiness for Change, Planfulness, Using Resources, and Intentional Behavior) and distress (k = 4) and wellness (k = 7) yielded similar results to the total score analyses.
Surviving Toward College Graduation
Authors: Lapan Richard T. , Poynton Timothy A.
Published: September 2023

This 5‐year longitudinal study with a diverse sample of 405 graduating high school seniors examined the person, behavior, and environment (PBE) factors that increased student chances of deciding to attend a 2‐ or 4‐year college, enrolling in college the fall semester immediately following high school graduation, and then returning to that same college a year later as a retained college student. Survivability across these three critical college‐going transitions was a function of two different kinds of PBE patterns. First, certain PBE factors played prominent roles at specific transition points and then more minor support roles at others. Second, several factors provided consistent support at each transition point without being the primary determiner of success at any single transition. Students are more likely to succeed in college if school counselors help them to learn and take advantage of those PBE patterns that promote postsecondary success.
Mixed‐Design Training Outcomes for Fellows Serving At‐Risk Youth Within Integrated Care Settings
Authors: Brubaker Michael D. , La Guardia Amanda C.
Published: September 2023

We used an exploratory mixed‐methods design with single‐case comparative analysis and analysis of covariance to evaluate the potential effectiveness of an interprofessional clinical training in a mental health counseling program. Initial findings indicate those engaging in specialized learning experiences that attended to critical aspects of youth behavioral health care experienced benefits with regard to their professional development, interprofessional socialization and valuing, and counseling self‐efficacy. Implications for the usefulness of trainings focused on interprofessional experiences are framed in relation to professional trends concerning integrated health care.
Protein intake in cancer: Does it improve nutritional status and/or modify tumour response to chemotherapy?
Authors: Boutière Martin , Cottet‐Rousselle Cécile , Coppard Céline , Couturier Karine , Féart Catherine , Couchet Morgane , Corne Christelle , Moinard Christophe , Breuillard Charlotte
Published: September 2023

Background

Combating malnutrition and cachexia is a core challenge in oncology. To limit muscle mass loss, the use of proteins in cancer is encouraged by experts in the field, but it is still debated due to their antagonist effects. Indeed, a high protein intake could preserve lean body mass but may promote tumour growth, whereas a low‐protein diet could reduce tumour size but without addressing cachexia. Here we used a realistic rodent model of cancer and chemotherapy to evaluate the influence of different protein intakes on cachexia, tumour response to chemotherapy and immune system response. The goal is to gain a closer understanding of the effect of protein intake in cancer patients undergoing chemotherapy.

Methods

Female Fischer 344 rats were divided into six groups: five groups (n = 14 per group) with cancer (Ward colon tumour) and chemotherapy were fed with isocaloric diets with 8%, 12%, 16%, 24% or 32% of caloric intake from protein and one healthy control group (n = 8) fed a 16% protein diet, considered as a standard diet. Chemotherapy included two cycles, 1 week apart, each consisting of an injection of CPT‐11 (50 mg/kg) followed by 5‐fluorouracil (50 mg/kg) the day after. Food intake, body weight, and tumour size were measured daily. On day 9, the rats were euthanized and organs were weighed. Body composition was determined and protein content and protein synthesis (SUnSET method) were measured in the muscle, liver, intestine, and tumour. Immune function was explored by flow cytometry.

Results

Cancer and chemotherapy led to a decrease in body weight characterized by a decrease of both fat mass (−56 ± 3%, P < 0.05) and fat‐free mass (−8 ± 1%, P < 0.05). Surprisingly, there was no effect of protein diet on body composition, muscle or tumour parameters (weight, protein content, or protein synthesis) but a high cumulative protein intake was positively associated with a high relative body weight and high fat‐free mass. The immune system was impacted by cancer and chemotherapy but not by the different amount of protein intake.

Conclusions

Using a realistic model of cancer and chemotherapy, we demonstrated for the first time that protein intake did not positively or negatively modulate tumour growth. Moreover, our results suggested that a high cumulative protein intake was able to improve moderately nutritional status in chemotherapy treated cancer rodents. Although this work cannot be evaluated clinically for ethical reasons, it nevertheless brings an essential contribution to nutrition management for cancer patients.
Application of the D3‐creatine muscle mass assessment tool to a geriatric weight loss trial: A pilot study
Authors: Beavers Kristen M. , Avery Allison E. , Shankaran Mahalakshmi , Evans William J. , Lynch S. Delanie , Dwyer Caitlyn , Howard Marjorie , Beavers Daniel P. , Weaver Ashley A. , Lenchik Leon , Cawthon Peggy M.
Published: September 2023

Background

Traditionally, weight loss (WL) trials utilize dual energy X‐ray absorptiometry (DXA) to measure lean mass. This method assumes lean mass, as the sum of all non‐bone and non‐fat tissue, is a reasonable proxy for muscle mass. In contrast, the D3‐creatine (D3Cr) dilution method directly measures whole body skeletal muscle mass, although this method has yet to be applied in the context of a geriatric WL trial. The purpose of this project was to (1) describe estimates of change and variability in D3Cr muscle mass in older adults participating in an intentional WL intervention and (2) relate its change to other measures of body composition as well as muscle function and strength.

Methods

The INVEST in Bone Health trial (NCT04076618), used as a scaffold for this ancillary pilot project, is a three‐armed, 12‐month randomized, controlled trial designed to determine the effects of resistance training or weighted vest use during intentional WL on a battery of musculoskeletal health outcomes among 150 older adults living with obesity. A convenience sample of 24 participants (n = 8/arm) are included in this analysis. At baseline and 6 months, participants were weighed, ingested a 30 mg D3Cr tracer dose, provided a fasted urine sample 3–6 days post‐dosage, underwent DXA (total body fat and lean masses, appendicular lean mass) and computed tomography (mid‐thigh and trunk muscle/intermuscular fat areas) scans, and performed 400‐m walk, stair climb, knee extensor strength, and grip strength tests.

Results

Participants were older (68.0 ± 4.4 years), mostly White (75.0%), predominantly female (66.7%), and living with obesity (body mass index: 33.8 ± 2.7 kg/m2). Six month total body WL was −10.3 (95% confidence interval, CI: −12.7, −7.9) kg. All DXA and computed tomography‐derived body composition measures were significantly decreased from baseline, yet D3Cr muscle mass did not change [+0.5 (95% CI: −2.0, 3.0) kg]. Of muscle function and strength measures, only grip strength significantly changed [+2.5 (95% CI: 1.0, 4.0) kg] from baseline.

Conclusions

Among 24 older adults, significant WL with or without weighted vest use or resistance training over a 6‐month period was associated with significant declines in all bioimaging metrics, while D3Cr muscle mass and muscle function and strength were preserved. Treatment assignment for the trial remains blinded; therefore, full interpretation of these findings is limited. Future work in this area will assess change in D3Cr muscle mass by parent trial treatment group assignment in all study participants.
Sustained improvements by behavioural parent training for children with attention‐deficit/hyperactivity disorder: A meta‐analytic review of longer‐term child and parental outcomes
Authors: Doffer Dominique P. A. , Dekkers Tycho J. , Hornstra Rianne , van der Oord Saskia , Luman Marjolein , Leijten Patty , Hoekstra Pieter J. , van den Hoofdakker Barbara J. , Groenman Annabeth P.
Published: September 2023

Background

Behavioural parent training is an evidence‐based intervention for children with attention‐deficit/hyperactivity disorder (ADHD), but little is known about the extent to which initial benefits are maintained.

Aims

This meta‐analytic review investigated longer‐term (i.e., more than 2 months post‐intervention) child and parental outcomes of behavioural parent training for children with ADHD.

Materials & Methods

We searched for randomized controlled trials and examined ADHD symptoms, behavioural problems, positive parenting, negative parenting, parenting sense of competence, parent‐child relationship quality, and parental mental health as outcomes. We included 27 studies (31 interventions; 217 effect sizes), used multilevel random‐effects meta‐analyses for between‐ and within‐group comparisons (pre‐intervention to follow‐up and post‐intervention to follow‐up), and explored twelve predictors of change.

Results

Between pre‐intervention and follow‐up (M = 5.3 months), we found significant small‐to‐moderate between‐group effects of the intervention on ADHD symptoms, behavioural problems, positive parenting, parenting sense of competence and parent‐child relationship quality. Within‐group findings show sustained improvements in the intervention conditions for all outcome domains. There were few significant changes from post‐intervention to follow‐up. Additionally, the large majority of the individual effect sizes indicated sustained outcomes from post‐intervention to follow‐up. There were seven significant predictors of change in child outcomes, including stronger reductions in ADHD symptoms of girls and behaviour problems of younger children. In contrast with some meta‐analyses on short‐term effects, we found no differences between masked and unmasked outcomes on ADHD symptoms at follow‐up.

Discussion & Conclusion

We conclude that behavioural parent training has longer‐term benefits for children's ADHD symptoms and behavioural problems, and for positive parenting behaviours, parenting sense of competence and quality of the parent‐child relationship.
Monitoring of leucine‐rich alpha‐2‐glycoprotein and assessment by small bowel capsule endoscopy are prognostic for Crohn's disease patients
Authors: Ito Takahiro , Dai Kazuki , Horiuchi Masashi , Horii Toshiki , Furukawa Shigeru , Maemoto Atsuo
Published: September 2023

Background and Aim

Endoscopy is important to determine the effectiveness of treatment for Crohn's disease (CD), but searching the entire small intestine is difficult. Thus, we investigated the usefulness of leucine‐rich alpha‐2 glycoprotein (LRG), a new biomarker for predicting mucosal activity, in evaluating the activity of CD small intestinal lesions. This will further determine whether the results of small bowel capsule endoscopy (SBCE) affect the prognosis of patients with CD.

Methods

A total of 114 patients with CD who underwent SBCE were included. We analyzed the correlation between LRG and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). The cutoff value of LRG to achieve mucosal healing was calculated using the receiver operating characteristic curve. Then, we compared the presence or absence of intervention and the relapse rate of patients who could not achieve mucosal healing.

Results

The CECDAI correlated with LRG. The calculated LRG value for achieving mucosal healing was ≤11.9. Ninety‐one patients were in clinical remission at the time of SBCE. During the follow‐up period, 17 patients relapsed. As a result of SBCE, when no treatment intervention was performed in the case of CECDAI ≥3.5, the relapse rate was significantly higher than when CECDAI <3.5 or intervention was performed in the case of CECDAI ≥3.5.

Conclusions

The results reveal that LRG correlates with the activity of the entire small intestine and that SBCE assessment and therapeutic intervention can influence patient prognosis.
Synthesis, characterization of new α‐quinolin‐3‐yl‐α‐(aminoamides, aminoesters) and bi‐heterocyclic aromatic systems from gem‐dicyanoepoxides and their pharmacological activity as antioxidant and antifungal agents
Authors: Bouria Houria , Alliouche Hayette , Chouiter Mohamed Imed , Bouraiou Abdelmalek , Merazig Hocine , Silva Artur M. S. , Belfaitah Ali
Published: September 2023

New series of quinoline coupled to diversely functionalized heterocyclic cores were synthesized, via appropriate synthetic routes, using 3‐(quinolin‐3‐yl) oxirane‐2,2‐carbonitriles as key intermediates. The epoxide ring opening gave bi‐heterocyclic hybrids such as α‐quinolin‐3‐yl‐α‐aminoacetic acid derivatives, quinoxaline‐ and benzimidazole‐quinoline hybrids, and quinoline‐1,3‐oxathioles. Some selected bi‐heterocyclic hybrids were evaluated in vitro for their antioxidant potential using DPPH• and ABTS•+ methods, and their antifungal activity against Fusarium oxysporum f. sp. Lycopersici. It was demonstrated that bi‐heterocyclic aromatic systems exhibited significant antioxidant activities, which are similar in magnitude to those of standards BHT and BHA with important IC50 values. The SAR study of the antifungal activity revealed that only compounds bearing a 2‐imino‐1,3‐oxathiole nucleus are active showing interesting results. Crystal X‐ray structures for two compounds are also reported.
Study of the 99mTc‐labeling conditions of 6‐hydrazinonicotinamide‐conjugated peptides from a new perspective: Introduction to the term radio‐stoichiometry
Authors: Kaihani Sajad , Sadeghzadeh Nourollah
Published: September 2023

Specific tumor uptake of peptide radiopharmaceuticals depends on tumor binding affinity and their radiochemical purity. Several important parameters that influence the 99mTc‐labeling and consequently the radiochemical purity of 6‐hydrazinonicotinamide (HYNIC)‐conjugated peptide are radionuclide activity, the amount of peptide, the amount of coligands, and the amount of reducing agents (stannous ion). In this review article, we have attempted studying these parameters in the HYNIC‐conjugated peptides (somatostatin, cholecystokinin/gastrin, bombesin, and RGD analogs) from a new perspective to obtain most used and optimized radio‐stoichiometric relationships. One of the most important results in this review is that for 99mTc‐labeling of HYNIC‐conjugated peptides, it is better to consider the most calculated mole ratio between technetium‐99m and the peptide (mole ratio of technetium‐99m to the peptide 1:200–400). The statistical results also show that among these 99mTc‐labeled peptides, the most used and favorable coligand is tricine/EDDA with two to one (2:1) mole ratio. These optimized radio‐stoichiometric relationships, favorable coligand mole ratio, and applicable radiolabeling points can greatly improve the labeling process of the HYNIC‐conjugated peptides, by reducing trial and error, increasing specific activity, and saving materials.
Casein phosphopeptide calcium chelation: preparation optimization, in vitro gastrointestinal simulated digestion, and peptide fragment exploration
Authors: Wang Ying , Wang Ruixue , Bai Huasong , Wang Songjun , Liu Tong , Zhang Xin , Wang Zhanzhong
Published: September 2023

BACKGROUND

Calcium is important in the formation of bones and teeth, cell metabolism, and other physiological activities. In this work, casein phosphopeptide‐calcium chelate (CPP‐Ca) was synthesized and the optimal process parameters for the chelation reaction were obtained. The bioavailability of calcium in CPP‐Ca was investigated by in vitro gastrointestinal simulated digestion. The existence of phytic acid and oxalic acid in the digestion system was evaluated to clarify the calcium holding ability of casein phosphopeptide (CPP). Liquid chromatography–tandem mass spectrometry (LC‐MS/MS) was used to identify oligopeptides from CPP‐Ca.

RESULTS

The optimal process parameters for the chelation reaction were: peptide concentration 7.76 mgmL−1, pH 8.54, and reaction temperature 43.3 °C. The digestion in vitro results indicated that the calcium release rate of CPP‐Ca in the stomach for 2 h reached 85%, and about 50% of the ionized calcium was re‐chelated with CPP in the intestine. Phytic acid and oxalic acid could lead to a sharp decrease in soluble calcium but around 50% of the calcium was still retained in the form of chelates in the presence of CPP. The LC‐MS/MS identified 19 casein‐derived oligopeptides after digestion, and calcium modifications were found on eight peptides derived from β‐casein and αs2‐casein.

CONCLUSIONS

This study clarified the excellent calcium holding capacity of CPP in the presence of phytic acid and oxalic acid. Liquid chromatography–tandem mass spectrometry also revealed peptide changes, and identified peptides that chelate with calcium. These findings provided significant insights that could be relevant to the further utilization and product development of peptide‐calcium chelate in the food industry. © 2023 Society of Chemical Industry.
Polyacrylamide Grafted Activated Carbon by Surface‐Initiated AGET ATRP for the Flocculation of MFT
Authors: Bégin Sarah Julie , Scotland Kevin Malcolm , Pede Paul Raivo , Vreugdenhil Andrew James
Published: September 2023

Polyacrylamide (PAM) is grafted from the surface of activated carbon (AC) by surface‐initiated activators generated by electron transfer atom transfer radical polymerization (SI‐AGET ATRP). This is accomplished by pre‐functionalizing the surface of activated carbon by oxidation, followed by the attachment of an ATRP initiator. From this surface, SI‐AGET ATRP of acrylamide monomers is performed. The resulting AC‐PAM is characterized by FTIR, XPS, TGA, and BET analysis. Additionally, the grafted polymer is cleaved from the surface of AC and its molecular weight distribution is measured by SEC. This material is designed to explore the effect that grafting a polymer flocculant onto AC will have on the polymer's flocculating abilities. This is evaluated by measuring the flocculation and dewatering of mature fine tailings (MFT) when dosed with the AC‐PAM compared to PAM. In all, this work demonstrates the successful grafting of PAM onto AC, as well as potential wastewater applications for this composite material.
Dip Coating of Water‐Resistant PEDOT:PSS Films Based on Physical Crosslinking
Authors: Yamamoto Shunsuke , Miyako Ryusei , Maeda Ryota , Ishizaki Yuya , Mitsuishi Masaya
Published: September 2023

Water‐resistant poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films are valuable in biomedical applications; however, they typically require crosslinkers to stabilize the films, which can introduce undesired aggregation or phase separation reactions. Herein, a dipping‐based process to prepare PEDOT:PSS films on nonplanar surfaces without crosslinker is developed. Sequential soaking of a dip‐coated PEDOT:PSS film in ethanol and water imparts water resistance to the film. Microscopic and spectroscopic techniques are used to monitor the process and confirm that the ethanol soaking elutes the excess PSS from the film bulk, which stabilizes the film prior to the water‐soaking process. The obtained films act as conductors and semiconductors on curved surfaces, including 3D‐printed objects. A film deposited on a curved surface is successfully applied as the channel layer in a neuromorphic organic electrochemical transistor. This approach can enable integrated bioelectronic and neuromorphic applications that can be readily deployed for facile prototyping.
Embedding of octonion Fourier transform in geometric algebra of ℝ3 and polar representations of octonion analytic signals in detail
Authors: Hitzer Eckhard
Published: September 2023

We show how the octonion Fourier transform can be embedded and studied in Clifford geometric algebra of three‐dimensional Euclidean space
. We apply a new form of dimensionally minimal embedding of octonions in geometric algebra that expresses octonion multiplication nonassociativity with a sum of up to four (individually associative) geometric algebra product terms. This approach leads to new polar representations of octonion analytic signals and signal reconstruction formulas.
Mapping of 1H NMR chemical shifts relationship with chemical similarities for the acceleration of metabolic profiling: Application on blood products
Authors: Takis Panteleimon G. , Aggelidou Varvara A. , Sands Caroline J. , Louka Alexandra
Published: September 2023

One‐dimensional (1D) proton‐nuclear magnetic resonance (1H‐NMR) spectroscopy is an established technique for the deconvolution of complex biological sample types via the identification/quantification of small molecules. It is highly reproducible and could be easily automated for small to large‐scale bioanalytical, epidemiological, and in general metabolomics studies. However, chemical shift variability is a serious issue that must still be solved in order to fully automate metabolite identification. Herein, we demonstrate a strategy to increase the confidence in assignments and effectively predict the chemical shifts of various NMR signals based upon the simplest form of statistical models (i.e., linear regression). To build these models, we were guided by chemical homology in serum/plasma metabolites classes (i.e., amino acids and carboxylic acids) and similarity between chemical groups such as methyl protons. Our models, built on 940 serum samples and validated in an independent cohort of 1,052 plasma‐EDTA spectra, were able to successfully predict the 1H NMR chemical shifts of 15 metabolites within ~1.5 linewidths (Δv1/2) error range on average. This pilot study demonstrates the potential of developing an algorithm for the accurate assignment of 1H NMR chemical shifts based solely on chemically defined constraints.
Rapid T2∗‐weighted MRI using multishot EPI with retrospective motion and phase correction in the emergency department
Authors: Li Zhiqiang , Ooi Melvyn B. , Murchison James A. , Karis John P.
Published: September 2023

Purpose

Brain MRI is increasingly used in the emergency department (ED), where ‐weighted MRI is an essential tool for detecting hemorrhage and stroke. The goal of this study was to develop a rapid ‐weighted MRI technique capable of correcting motion‐induced artifacts, thereby simultaneously improving scan time and motion robustness for ED applications.

Methods

A 2D gradient‐echo (GRE)–based multishot EPI (msEPI) technique was implemented using a navigator echo for estimating motion‐induced errors. Bulk rigid head motion and phase errors were retrospectively corrected using an iterative conjugate gradient approach in the reconstruction pipeline. Three volunteers and select patients were imaged at 3 T and/or 1.5 T with an approximately 1‐min full‐brain protocol using the proposed msEPI technique and compared to an approximately 3‐min standard‐of‐care GRE protocol to examine its performance.

Results

Data from volunteers demonstrated that in‐plane motion artifacts could be effectively corrected with the proposed msEPI technique, and through‐plane motion artifacts could be mitigated. Patient images were qualitatively reviewed by one radiologist without a formal statistical analysis. These results suggested the proposed technique could correct motion‐induced artifacts in the clinical setting. In addition, the conspicuity of susceptibility‐related lesions using the proposed msEPI technique was comparable, or improved, compared to GRE.

Conclusion

A 1‐min full‐brain ‐weighted MRI technique was developed using msEPI with a navigator echo to correct motion‐induced errors. Preliminary clinical results suggest faster scans and improved motion robustness and lesion conspicuity make msEPI a competitive alternative to traditional ‐weighted MRI techniques for brain studies in the ED.
Probabilistic analysis of width‐limited 3D slope in spatially variable soils: UBLA enhanced with efficiency‐improved discretization of horn‐like failure mechanism
Authors: Sun Zhibin , Zhao Yang , Hu Yining , Dias Daniel , Ji Jian
Published: September 2023

Reliability analysis of earth slopes considering soil spatial variability has garnered significant attention from researchers. However, previous studies have predominantly focused on long slopes with infinite or ample width, such as dams and subgrades, but rare research was dedicated to slopes with width restricted by boundary constraints. In this regard, this paper proposes an efficient reliability framework suitable for width‐limited slopes in spatially variable soils. The proposed framework employed spatial discretization‐based upper bound limit analysis (UBLA) to conduct the deterministic slope stability analysis. The established failure mechanism can well capture the width‐limited three‐dimensional slip surface characteristics and satisfies the kinematically admissible conditions in spatially variable soils. Two innovative strategies are proposed to boost the efficiency of the discretized mechanism. They reduce the computational time to determine safety factors from over 20 min to less than 2 min. For the uncertainty modeling and slope reliability computing procedure, the Sparse Polynomial Chaos Expansion (SPCE) and Monte Carlo Simulation (MCS) methods are combined to generate the distribution of safety factors and failure probabilities. This combination addresses the high‐dimensional stochastic problem arising from 3D spatial variability. Using the proposed framework, a parametric analysis of a 3D spatially variable slope is conducted to investigate the impact of various factors. The findings of this paper are beneficial to the risk evolution of width‐limited slopes, and the efficiency enhancement strategies have the potential to expedite the limit analysis of other geo‐structures, such as tunnels, retaining walls, and foundations.
Use of oral diet and nutrition support in management of stricturing and fistulizing Crohn's disease
Authors: Fansiwala Kush , Shah Neha D. , McNulty Kelly A. , Kwaan Mary R. , Limketkai Berkeley N.
Published: September 2023

Crohn's disease (CD), a form of inflammatory bowel disease, involves chronic inflammation within the gastrointestinal tract. Intestinal strictures and fistulas are common complications of CD with varying severity in their presentations. Modifications in oral diet or use of exclusive enteral nutrition (EEN) are common approaches to manage both stricturing and fistulizing disease, although supporting research evidence is generally limited. In the preoperative period, there is strong evidence that EEN can reduce surgical complications. Parenteral nutrition (PN) is often utilized in the management of enterocutaneous fistulas, given that oral diet and EEN may potentially increase output in proximal fistulas. This narrative review highlights the current practices and evidence for the roles of oral diet, EEN, and PN in treatment and management of stricturing and fistulizing CD.
A time‐domain boundary element method for the 3D dissipative wave equation: Case of Neumann problems
Authors: Takahashi Toru
Published: September 2023

The present article proposes a time‐domain boundary element method (TDBEM) for the three‐dimensional (3D) dissipative wave equation (DWE). Although the fundamental ingredients such as the Green's function for the 3D DWE have been known for a long time, the details of formulation and implementation for such a 3D TDBEM have been unreported yet to the author's best knowledge. The present formulation is performed truly in time domain on the basis of the time‐dependent Green's function and results in a marching‐on‐in‐time fashion. The main concern is in the evaluation of the boundary integrals. For this regard, weakly‐ and removable‐singularities are carefully treated. The proposed TDBEM is checked through the numerical examples whose solutions can be obtained semi‐analytically by means of the inverse Laplace transform. The results of the present TDBEM are satisfactory to validate its formulation and implementation for Neumann problems. On the other hand, the present formulation based on the ordinary boundary integral equation (BIE) is unstable for Dirichlet problems. The numerical analyses for the non‐dissipative case imply that the instability issue can be partially resolved by using the Burton–Miller BIE even in the dissipative case.
DNA methylation status of SHATI/NAT8L promoter in the blood of cigarette smokers
Authors: Izuo Naotaka , Miyanishi Hajime , Nishizawa Daisuke , Fujii Takuma , Hasegawa Junko , Sato Naomi , Tanioka Fumihiko , Sugimura Haruhiko , Ikeda Kazutaka , Nitta Atsumi
Published: September 2023

Aims

Cigarette smoking is a preventable risk factor for various diseases such as cancer, ischemic stroke, cardiac stroke, and chronic obstructive pulmonary disease. Smoking cessation is of great importance not only for individual smokers but also for social health. Regarding current cessation therapies, the effectiveness of nicotine replacement is limited, and the cost of varenicline medication is considerable. Thus, a method for screening smokers who are responsive to cessation therapy based on the therapeutic effectiveness is required. Peripheral biomarkers reflecting smoking dependence status are necessary to establish a method for achieving effective cessation therapy.

Methods

Methylation status of smokers' blood DNA was evaluated focusing on SHATI/NAT8L, an addiction‐related gene. Eight CpG sites in SHATI/NAT8L were quantified by pyrosequencing.

Results

There was no difference in the methylation status of this gene between smokers (n = 129) and non‐smokers (n = 129) at all CpG sites. No correlations between the methylation status of SHATI/NAT8L and indicators of smoking dependence were found.

Conclusions

Although the present study found no significance in the DNA methylation of SHATI/NAT8L among smokers, the exploration of predictable peripheral biomarkers for the effectiveness of smoking cessation therapy is required.
The Effects of Adenotonsillectomy for Obstructive Sleep Apnea on Growth Trajectory in Children With Obesity
Authors: Kashiwazaki Ryota , Jensen Alexandria M. , Haemer Matthew , Friedman Norman R.
Published: September 2023

Objective

To analyze the growth trajectory of children with obesity before and after adenotonsillectomy (T&A). We hypothesize that T&A will not affect the growth trajectory but children in a multidisciplinary weight management program (MWMP) will have a healthier growth trajectory.

Study Design

Retrospective review.

Setting

Tertiary Children's Hospital.

Methods

Body mass index (BMI) trajectories of nonsyndromic children with obesity and obstructive sleep apnea (OSA) who underwent T&A were analyzed. A linear mixed effects model was fit to the BMI expressed as a percentage of the 95th percentile (%BMIp95) data. Covariates included demographic variables, pre‐ and postoperative participation in an MWMP, baseline obesity class, and time. We explored clinically meaningful interactions. BMI slope estimates before and after surgery were calculated and compared for baseline obesity classification and postoperative MWMP visits.

Results

A total of 177 patients, 58% male with a mean age of 9.7 years at the time of surgery, were studied. Higher baseline obesity class (II and III), time, the interaction between obesity class III and elapsed time relative to surgical date, and the interaction between obesity class III and the postsurgical period were all significantly associated with the outcome of %BMIp95 (P < .05). There was a significantly higher %BMIp95 trajectory following surgery in patients with baseline obesity class III who did not have any postoperative MWMP visits (P < .001). Preoperative obesity visits, however, were not significantly associated with postoperative growth.

Conclusion

The association between T&A and weight trajectory depends upon obesity class and participation in a MWMP. Coordinated care of children with obesity between otolaryngologists and an MWMP may improve OSA and obesity outcomes.

Level of Evidence

The level of evidence: 3.
A bulk‐surface model for the electrothermal feedback in large‐area organic light‐emitting diodes
Authors: Glitzky Annegret , Liero Matthias
Published: September 2023

This work deals with an effective bulk‐surface thermistor model describing the electrothermal behavior of large‐area thin‐film organic light‐emitting diodes (OLEDs). This model was rigorously derived from a ‐Laplace thermistor model by dimension reduction and consists of the heat equation in the three‐dimensional glass substrate and two semi‐linear equations describing the current flow through the electrodes coupled to algebraic equations that express the continuity of the electrical fluxes through the organic layers. The electrical problem lives on the surface of the glass substrate where the OLED is mounted. The source terms in the heat equation result from Joule heating and are concentrated on the part of the boundary where the current‐flow problem is formulated. Schauder's fixed‐point theorem is used to establish the existence of weak solutions to this effective system. Since the heat source terms at the surface are a priori only in L1, the concept of entropy solutions for the heat equation is worked with.