bluuebunny/crossref_metadata_2025 huggingface dataset:
MEK1/2‐ and ERK1/2‐Mediated Lung Endothelial Injury and Altered Hemostasis Promote Diffuse Alveolar Hemorrhage in Murine Lupus
Authors: Zhuang Haoyang , Han Shuhong , Harris Neil S. , Reeves Westley H.
Published: June 2024

Objective

About 3% of patients with lupus develop severe diffuse alveolar hemorrhage (DAH) with pulmonary vasculitis. C57BL/6 (B6) mice with pristane‐induced lupus also develop DAH, but BALB/c mice are resistant. DAH is independent of Toll‐like receptor signaling and other inflammatory pathways. This study examined the role of the MEK1/2 pathway (MEK1/2–ERK1/2, JNK, p38).

Methods

B6 and BALB/c mice were treated with pristane with or without inhibitors of MEK1/2 (trametinib/GSK1120212 [GSK]), ERK1/2 (SCH772984 [SCH]), JNK, or p38. Effects on lung hemorrhage and hemostasis were determined.

Results

GSK and SCH abolished DAH, whereas JNK and p38 inhibitors were ineffective. Apoptotic cells were present in lung samples from pristane‐treated mice but not in mice receiving pristane and GSK, and endothelial dysfunction was normalized. Expression of the ERK1/2‐regulated transcription factor early growth response 1 increased in pristane‐treated B6, but not BALB/c, mice and was normalized by GSK. Pristane also increased expression of the anticoagulant genes Tfpi and Thbd in B6 mice. The ratio of Tfpi to tissue factor (F3) to Tfpi increased in B6 (but not BALB/c) mice and was normalized by GSK. Circulating thrombomodulin protein levels increased in B6 mice and returned to normal after GSK treatment. Consistent with augmented endothelial anticoagulant activity, pristane treatment increased tail bleeding in B6 mice.

Conclusion

Pristane treatment promotes lung endothelial injury and DAH in B6 mice by activating the MEK1/2–ERK1/2 pathway and impairing hemostasis. The hereditary factors determining susceptibility to lung injury and bleeding in pristane‐induced lupus are relevant to the pathophysiology of life‐threatening DAH in systemic lupus erythematosus and may help to optimize therapy.
Observer‐based adaptive time‐varying bipartite formation tracking of multi‐agent systems with multiple nonautonomous leaders
Authors: Wei Ge , Wu Jie , Zhan Xisheng , Wu Bo , Yan Huaicheng
Published: June 2024

In this article, the problem of bipartite time‐varying formation (BTVF) tracking for multi‐agent systems (MASs) under signed digraphs is investigated, in which the inputs of leaders are unknown and bounded. A novel kind of adaptive nonsmooth BTVF tracking protocol for MASs is proposed that did not utilize eigenvalue of Laplacian matrix. Based on the state observer, the problem that the system states are not measurable is solved. In addition, in order to avoid undesirable chattering caused by leaders' nonzero inputs, continuous protocols are proposed. And in this case, the error is uniformly ultimately bounded. Lyapunov method reflects the convergence analysis of the submitted protocols. At last, the desired theoretical results are achieved on a multirobot system.
Synthesis, structural, and optical behavior of erbium‐doped silicophosphate glasses for photonics applications
Authors: Bouabdalli El Mahdi , El Jouad Mohamed , Touhtouh Samira , Chellakhi Abdelkhalek , Hajjaji Abdelowahed
Published: June 2024

Erbium‐incorporated silicophosphate glasses are very desirable in principal sectors such as photonics, optoelectronics, lasers, and illuminating diodes. The focus of the current investigation has been on determining how the erbium dopant affects the optical, physical, and structural characteristics of the silicophosphate‐based glasses. The pure silicophosphate glasses and doped with various contents of erbium were prepared by the sol–gel process in this work. The noncrystalline character of the glasses synthesized was confirmed by the XRD patterns that were obtained. The optical measurement showed that the addition of trivalent erbium ions resulted in an increase in the refractive index of the samples and a decrease in their energy band gap values. It demonstrated the presence of P–O–P linkage stretching vibration modes that were both symmetrical and asymmetrical, P–O in PO4 bending vibration modes, OH group elongating and flexure vibrations, and P–O–H water absorption in glasses. The theoretical values of the optical basicity (Ʌth) increased from 0.465 to 0.472, while the values of the interaction parameter (A) decreased from 0.218 to 0.214 . Silicophosphate glasses doped with trivalent erbium ions show promise as optoelectronic and optical filter system materials.
Novel benzothiazole–pyrazoline–styrene hybrid for ultrasensitive detection of Hg(II) ions: Synthesis and chemosensor evaluation
Authors: Ratnawati Devi , Kartini Indriana , Pranowo Harno Dwi , Kurniawan Yehezkiel Steven , Wahyuningsih Tutik Dwi
Published: June 2024

Water pollution has become a serious issue, and mercury(II) ion (Hg(II)) is highly toxic even at low concentrations. Therefore, Hg(II) concentration should be strictly monitored. This study evaluated pyrazoline compounds as fluorescence chemosensor agents for Hg(II) detection. These compounds were prepared from vanillin via etherification, Claisen–Schmidt, and cyclocondensation reactions, to yield benzothiazole–pyrazoline–styrene hybrid compounds. The hybrid compound without styrene was successfully synthesized in 97.70% yield with limit of detection (LoD) and limit of quantification (LoQ) values of 323.5 and 1078 μM, respectively. Conversely, the hybrid compound was produced in 97.29% yield with the LoD and LoQ values of 8.94 and 29.79 nM, respectively. Further spectroscopic investigations revealed that Hg(II) ions can either chelate with three nitrogen of pyridine, pyrazoline, and benzothiazole structures or two oxygen of vanillin and styrene. Furthermore, the hybrid compound was successfully applied in the direct quantification of Hg(II) ions in tap and underground water samples with a validity of 91.63% and 86.08%, respectively, compared with mercury analyzer measurement. The regeneration of pyrazoline was also easily achieved via the addition of an ethylenediaminetetraacetic acid solution. These findings show the promising application of the benzothiazole–pyrazoline–styrene hybrid compound for Hg(II) monitoring in real environmental samples.
Improvement of TaC9‐ABE mediated correction of human SMN2 gene
Authors: Peng Xiaohua , Chi Yue , Wang Jinling , Li Shuangpeng , Liu Yang , Tang Chengcheng , Zhou Xiaoqing , Lu Xuan , Gao Yue , Lai Liangxue , Chen Min , Zou Qingjian
Published: June 2024

Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Gene editing technology repairs the conversion of the 6th base T to C in exon 7 of the paralogous SMN2 gene, compensating for the SMN protein expression and promoting the survival and function of motor neurons. However, low editing efficiency and unintended off‐target effects limit the application of this technology. Here, we optimized a TaC9‐adenine base editor (ABE) system by combining Cas9 nickase with the transcription activator‐like effector (TALE)‐adenosine deaminase fusion protein to effectively and precisely edit SMN2 without detectable Cas9 dependent off‐target effects in human cell lines. We also generated human SMA‐induced pluripotent stem cells (SMA‐iPSCs) through the mutation of the splice acceptor or deletion of the exon 7 of SMN1. TaC9‐R10 induced 45% SMN2 T6 > C conversion in the SMA‐iPSCs. The SMN2 T6 > C splice‐corrected SMA‐iPSCs were directionally differentiated into motor neurons, exhibiting SMN protein recovery and antiapoptosis ability. Therefore, the TaC9‐ABE system with dual guides from the combination of Cas9 with TALE could be a potential therapeutic strategy for SMA with high efficacy and safety.
Radiomic score for lung nodules as a prognostic biomarker in locally advanced rectal cancer patients: A bi‐institutional study
Authors: Zhang Zhiyuan , Wang Jiazhou , Dai Di , Xia Fan , Sun Yiqun , Li Guichao , Wan Juefeng , Shen Lijun , Zhang Hui , Wang Yan , Zhong Jie , Bao Jun , Zhang Zhen
Published: June 2024

Background

Undetermined lung nodules are common in locally advanced rectal cancer (LARC) and lack precise risk stratification. This study aimed to develop a radiomic‐based score (Rad‐score) to distinguish metastasis and predict overall survival (OS) in patients with LARC and lung nodules.

Methods

Retrospective data from two institutions (July 10, 2006—September 24, 2015) was used to develop and validate the Rad‐score for distinguishing lung nodule malignancy. The prognostic value of the Rad‐score was investigated in LARC cohorts, leading to the construction and validation of a clinical and radiomic score (Cli‐Rad‐score) that incorporates both clinical and radiomic information for the purpose of improving personalized clinical prognosis prediction. Descriptive statistics, survival analysis, and model comparison were performed to assess the results.

Results

The Rad‐score demonstrated great performance in distinguishing malignancy, with C‐index values of 0.793 [95% CI: 0.729–0.856] in the training set and 0.730 [95% CI: 0.666–0.874] in the validation set. In independent LARC cohorts, Rad‐score validation achieved C‐index values of 0.794 [95% CI: 0.737–0.851] and 0.747 [95% CI: 0.615–0.879]. Regarding prognostic prediction, Rad‐score effectively stratified patients. Cli‐Rad‐score outperformed the clinicopathological information alone in risk stratification, as evidenced by significantly higher C‐index values (0.735 vs. 0.695 in the internal set and 0.618 vs. 0.595 in the external set).

Conclusions

CT‐based radiomics could serve as a reliable and powerful tool for lung nodule malignancy distinction and prognostic prediction in LARC patients. Rad‐score predicts prognosis independently. Incorporation of Cli‐Rad‐score significantly enhances the persionalized clinical prognostic capacity in LARC patients with lung nodules.
Challenges and perspectives in use of artificial intelligence to support treatment recommendations in clinical oncology
Authors: Duwe Gregor , Mercier Dominique , Wiesmann Crispin , Kauth Verena , Moench Kerstin , Junker Markus , Neumann Christopher C. M. , Haferkamp Axel , Dengel Andreas , Höfner Thomas
Published: June 2024

Artificial intelligence (AI) promises to be the next revolutionary step in modern society. Yet, its role in all fields of industry and science need to be determined. One very promising field is represented by AI‐based decision‐making tools in clinical oncology leading to more comprehensive, personalized therapy approaches. In this review, the authors provide an overview on all relevant technical applications of AI in oncology, which are required to understand the future challenges and realistic perspectives for decision‐making tools. In recent years, various applications of AI in medicine have been developed focusing on the analysis of radiological and pathological images. AI applications encompass large amounts of complex data supporting clinical decision‐making and reducing errors by objectively quantifying all aspects of the data collected. In clinical oncology, almost all patients receive a treatment recommendation in a multidisciplinary cancer conference at the beginning and during their treatment periods. These highly complex decisions are based on a large amount of information (of the patients and of the various treatment options), which need to be analyzed and correctly classified in a short time. In this review, the authors describe the technical and medical requirements of AI to address these scientific challenges in a multidisciplinary manner. Major challenges in the use of AI in oncology and decision‐making tools are data security, data representation, and explainability of AI‐based outcome predictions, in particular for decision‐making processes in multidisciplinary cancer conferences. Finally, limitations and potential solutions are described and compared for current and future research attempts.
Developing a minimum data standard for student mental health services in the UK: A qualitative study with staff from university support services
Authors: O'Donnell Jennifer , Broglia Emma , Turner Afra , Fudge Mark , Knowles Louise , Barkham Michael ,   SCORE Consortium
Published: June 2024

Objective

This study is part of the Student Counselling Outcomes Research and Evaluation (SCORE) initiative that is pooling university counselling service data to improve datasets and evidence for counselling in this sector. This study aimed to explore university counselling staff views about which data should be included in a national minimum data standard (MDS) to provide evidence for counselling in the sector.

Method

Semi‐structured focus groups were conducted with university counselling staff including counsellors, service leaders and mental health advisors. They explored data to include in an MDS, current data collection practices, service and sector level data collection barriers. Two researchers performed content analysis involving identifying fields for inclusion. Thematic analysis was used to identify contextual issues surrounding data collection. Ten focus groups were conducted with 41 participants across 26 university counselling services.

Results

Content analysis identified fields of information for the MDS within the categories of student characteristics, demographics, clinical assessment and service evaluation. Thematic analysis explored context and culture surrounding data collection, barriers and facilitators, institutional influence and ideal data collection practices. This highlights the need for service support and training around data collection, clear processes, and adequate IT infrastructure and staff resources.

Discussion

These findings will inform the development of an MDS as part of the SCORE study. The next stage will involve further development of the MDS and piloting in services. The longer term aim is to implement an MDS across university counselling services, enabling the growth of evidence for the sector which may allow increased funding and service provision.
Ultrasound‐Mediated Antibiotic Delivery to In Vivo Biofilm Infections: A Review
Authors: Liu Jamie D. , Van Treeck Kelly E. , Marston William A. , Papadopoulou Virginie , Rowe Sarah E.
Published: June 2024

Bacterial biofilms are a significant concern in various medical contexts due to their resilience to our immune system as well as antibiotic therapy. Biofilms often require surgical removal and frequently lead to recurrent or chronic infections. Therefore, there is an urgent need for improved strategies to treat biofilm infections. Ultrasound‐mediated drug delivery is a technique that combines ultrasound application, often with the administration of acoustically‐active agents, to enhance drug delivery to specific target tissues or cells within the body. This method involves using ultrasound waves to assist in the transportation or activation of medications, improving their penetration, distribution, and efficacy at the desired site. The advantages of ultrasound‐mediated drug delivery include targeted and localized delivery, reduced systemic side effects, and improved efficacy of the drug at lower doses. This review scrutinizes recent advances in the application of ultrasound‐mediated drug delivery for treating biofilm infections, focusing on in vivo studies. We examine the strengths and limitations of this technology in the context of wound infections, device‐associated infections, lung infections and abscesses, and discuss current gaps in knowledge and clinical translation considerations.
Uracil‐Selective Cross‐Linking in RNA and Inhibition of miRNA Function by 2‐Amino‐6‐vinyl‐7‐deazapurine Deoxynucleosides
Authors: Soemawisastra Nadya , Okamura Hidenori , Abdelhady Ahmed Mostafa , Onizuka Kazumitsu , Ozawa Mamiko , Nagatsugi Fumi
Published: June 2024

MicroRNAs (miRNAs) regulate gene expression through RNA interference. Consequently, miRNA inhibitors, such as anti‐miRNA oligonucleotides (AMOs), have attracted attention for treating miRNA overexpression. To achieve efficient inhibition, we developed 2‐amino‐6‐vinylpurine (AVP) nucleosides that form covalent bonds with uridine counterparts in RNA. We demonstrated that mRNA cross‐linked with AVP‐conjugated antisense oligonucleotides with AVP were protected from gene silencing by exogenous miRNA. However, endogenous miRNA function could not be inhibited in cells, probably because of slow cross‐linking kinetics. We recently developed ADpVP, an AVP derivative bearing a 7‐propynyl group – which boasts faster reaction rate than the original AVP. Here, we synthesized dADpVP – a deoxy analog of ADpVP – through a simplified synthesis protocol. Evaluation of the cross‐linking reaction revealed that the reaction kinetics of dADpVP were comparable to those of ADpVP. In addition, structural analysis of the cross‐linked adduct discovered N3 linkage against uridine. Incorporating dADpVP into two types of miRNA inhibitors revealed a marginal impact on AMO efficacy yet improved the performance of target site blockers. These results indicate the potential of cross‐linking nucleosides for indirect miRNA function inhibition.
Oxidation‐Responsive Supramolecular Hydrogels Based on Glucosamine Derivatives with an Aryl Sulfide Group
Authors: Ali Onaza , Okumura Bioru , Shintani Yuki , Sugiura Shintaro , Shibata Aya , Higashi Sayuri L. , Ikeda Masato
Published: June 2024

Supramolecular hydrogels can be obtained via self‐assembly of small molecules in aqueous environments. In this study, we describe the development of oxidation‐responsive supramolecular hydrogels comprising glucosamine derivatives with an aryl sulfide group. We demonstrate that hydrogen peroxide can induce a gel–sol transition through the oxidation of the sulfide group to the corresponding sulfoxide. Furthermore, we show that this oxidation responsiveness can be extended to photo‐responsiveness with the aid of a photosensitizer.
Electrocatalyst‐Hydrogel Polymer Nanocomposite Thin Films for Water Splitting
Authors: Bovas Anu , Radhakrishnan T. P.
Published: June 2024

Realization of scalable technologies for key processes like electrochemical water splitting requires the development of sustainable, efficient and cost‐effective catalytic electrodes. The innumerable electrocatalysts being developed in contemporary research rely on the use of a limited choice of binders for effective deployment in the electrolysis setting. Recent studies have demonstrated the utility of electrically insulating hydrogel polymers as suitable matrices for incorporating the electrocatalyst nanoparticles; the nanocomposite thin films coated on conducting substrates mediate highly efficient electrocatalytic water splitting reactions through the effective confinement of the electrolyte within and release of the gaseous products. After a brief introduction to the basic challenges in the field and the existing approaches that address them, this article outlines the promise of hydrogel based nanocomposite thin films in developing efficient and sustainable catalytic electrodes for water splitting, and their functional role in enhancing the efficiency of the electrochemical process. Directions for further development in this domain are noted.
Spiritual and religious competency training for mental health care professionals: How much is enough?
Authors: Vieten Cassandra , Fox Jesse , Oxhandler Holly K. , Pearce Michelle , Polson Edward C. , Pargament Kenneth , Wong Serena , Currier Joseph M.
Published: June 2024

Spirituality and religion (R/S) are important aspects of diversity and functioning for most people, and training in these areas for mental health professionals is needed. But how much training is enough? This paper proposes R/S training guidelines that can be used to inform coursework, practicum/internship didactic training, and supervision.
Bioequivalence of Recombinant Human Teriparatide Injection in Healthy Adult Female Subjects in the Fasting State
Authors: Hu Shengling , Wen Yalei , Li Jing , Chen Wenming , Bai Yichuan , Gong Fengyun
Published: June 2024

A single‐center, randomized, open, 2‐period, self‐crossover, single‐dose trial was conducted to evaluate the bioequivalence of the test (T) and reference (R) preparations in healthy adult female subjects under fasting conditions. Seventy‐six subjects were enrolled in the study, and subjects were randomly divided into 2 groups at a 1:1 ratio and were administered once per period, with a 4‐day washout period. In each period, plasma drug concentrations, blood calcium changes, and antibodies were determined for pharmacokinetics, pharmacodynamics, and immunogenicity analysis, respectively, and adverse events were recorded for safety analysis. The 90% confidence intervals for the geometric mean ratios (T:R) of maximum plasma concentration, area under the plasma concentration‐time curve from time 0 to the last measurable concentration, and area under the plasma concentration‐time curve from time 0 to infinity were within the predefined bioequivalence criterion of 80%‐125%, indicating bioequivalence between the T and R preparations under fasting conditions. Comparable serum calcium levels demonstrated pharmacodynamics similarity, and no differences were found in immunogenicity profiles. Additionally, the incidence of adverse reactions to the T preparation was 18.4% lower than that of the R preparation (31.6%). This study confirmed the bioequivalence of the T and R preparations under fasting conditions, along with comparable immunogenicity profiles and good safety.
Genesis of Polynitrogen Compounds Employing Silicon Substituted cyclo[18]carbon: A DFT Investigation
Authors: Sen Sobitri , Bag Arijit , Pal Sourav
Published: June 2024

Activation of molecular N2 and its catalytic ability to form NH3 using C17Si has been already reported. This current study reports the formation of exclusive polynitrogen clusters (N4 and N5) on the C17Si ring. The clusters are generated using N2 and N3 respectively. Physical and chemical property analyses of the clusters show that the N5 cluster exhibits greater stability than N4. The former is seen to experience reduced molecular strain compared to the latter owing to its co‐planar geometry. The thermodynamic calculations of the systems further show that the formation of the N5 cluster is spontaneous compared to N4 on the C17Si ring.
Enhancing environmental DNA metabarcoding from marine ecosystems: Impact of filter type, storage method, and storage time on the assessment of fish alpha and beta diversity
Authors: Bizzozzero Manuela R. , Altermatt Florian , Cicciarella Riccardo , Walser Jean‐Claude , Willems Erik P. , Krützen Michael
Published: June 2024

The collection of environmental DNA (eDNA) and subsequent metabarcoding are useful tools for assessing marine fish biodiversity noninvasively. It is of particular importance to evaluate biodiversity in regions that are hard to access and thus less well studied. Sampling and preservation methods tailored to the specific circumstances are required. Aquatic eDNA is often captured on filters made of different materials and pore sizes, and subsequently stored under divergent conditions for varying periods of time. Previous studies on multispecies detection in marine systems have primarily focused on capture and extraction effects. Our study, in contrast, examined the effects of filter type, storage method, and storage time on DNA yield, alpha (i.e., ZOTU richness) and beta diversity (i.e., ZOTU composition) recovered from a marine ecosystem in Shark Bay, Western Australia. We compared two different filter types (cellulose‐nitrate filters with pore sizes of 0.45 μm; glass‐fiber filters with pore sizes of 0.1 μm), two storage methods (preservation in Longmire's solution and drying, respectively), various storage times (30–68 days) on two metabarcoding assays using different fish‐specific primers. Our results showed that storage time decreased DNA yield and affected alpha and beta diversity estimates. Cellulose‐nitrate filters stored in Longmire's solution proved to be the best combination with the smallest decrease in DNA yield, no effect on alpha diversity and consistent community compositions. Storing glass‐fiber filters in Longmire's solution led to a decrease in eDNA yield and alpha diversity estimates with increasing storage time. Furthermore, the largest change in beta diversity for each metabarcode was found for glass‐fiber filters regardless of storage method. Our results highlight the importance of considering storage time and interactions between storage method and filter when analyzing eDNA results, especially when storing samples for an extended time period or comparison of samples stored for different durations.
Hybrid data‐driven and physics‐based simulation technique for seismic response evaluation of steel buckling‐restrained braced frames considering brace fracture
Authors: Sadrara Ali , Epackachi Siamak , Imanpour Ali , Kabir Mohammad Zaman
Published: June 2024

This paper proposes a hybrid data‐driven and physics‐based simulation technique for seismic response evaluation of steel Buckling‐Restrained Braced Frames (BRBFs) considering brace fracture. Buckling‐Restrained Brace (BRB) fracture is represented by cumulative plastic deformation capacity. A dataset, consisting of 95 past BRB laboratory tests and 120 simulated BRB responses generated using the finite element method, is first developed. An Artificial Neural Network‐based (ANN) predictive model is then trained using the training dataset to estimate the cumulative plastic deformation of BRBs. The prediction capability of the ANN‐based predictive model is validated using the training dataset and an existing regression‐based predictive model. In the second part of the paper, an hybrid simulation technique combining the data‐driven model and physics‐based numerical modeling is presented to conduct the nonlinear time history analysis, followed by 1) validation against a full‐scale BRBF testing and 2) demonstration of the proposed simulation technique using a six‐story BRBF. The results confirm that the proposed predictive model can predict the BRB fracture with sufficient accuracy. Furthermore, the hybrid data‐driven physics‐based simulation technique can be used as a powerful tool for dynamic analysis of BRBFs considering BRB fracture.
Honoring the authentic voices of Latina/o/e evaluators and the communities we serve
Authors: Aponte‐Soto Lisa , Casillas Wanda , Ali Asma , Maldonado Saúl I. , López‐Cevallos Daniel F.
Published: June 2024

This article provides a summary of the main themes discussed throughout thisNew Directions for Evaluation(NDE) issue. The issue underscores the importance of investing in Latina/o/e talent to increase the pipeline of Latina/o/e evaluators, committed to social justice who are trained in culturally responsive and equitable evaluation (CREE), with a Latina/o/e lens or LatCREE. The contributing authors of this issue offer LatCREE frameworks and approaches that center the voices of Latina/o/e communities to advance humanizing their assets and counter harmful status quo programs and services that are not aligned with the needs of communities and deplete resources. Furthermore, the current issue provides a deeper understanding of the perspectives and experiences of evaluators working with and for Latina/o/e communities. We offer an issue that critically engages voices that have been woefully absent to date, that of the Latina/o/e communities. In that sense, we hope it will spur discussions and raise questions about our role and responsibility as evaluators, to disrupt harmful practices, and to shed light on the issues impacting our communities and the culturally responsive approaches that may be used to address them.
Evaluation in gentrifying Latinx immigrant communities: Lessons learned from culturally responsive evaluation with youth
Authors: Ali Asma M. , León Jovita Murillo , Chávez Noé Rubén
Published: June 2024

Culturally responsive evaluation (CRE) efforts highlight the significance of lived experiences of Latinx communities by honoring these voices to inform decision‐making for more equitable support systems and resources. Gentrification disrupts both the physical and social community characteristics, causing shifts in the existing collective community identity and experience. However, CRE projects provide opportunities for marginalized youth community members to engage meaningfully with and better understand these community changes. We describe three projects conducted with community‐based youth researchers in the Mexican‐American US communities of Pilsen (Chicago) and South Los Angeles, exploring community‐personal identity and relationship shifts among evaluators and youth community members. Our article concludes with lessons learned for CRE evaluators working in gentrifying communities.
Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease
Authors: van Dijk Myrthe J. , Ruiter Titine J. J. , van der Veen Sigrid , Rab Minke A. E. , van Oirschot Brigitte A. , Bos Jennifer , Derichs Cleo , Rijneveld Anita W. , Cnossen Marjon H. , Nur Erfan , Biemond Bart J. , Bartels Marije , Schutgens Roger E. G. , van Solinge Wouter W. , Jans Judith J. M. , van Beers Eduard J. , van Wijk Richard
Published: June 2024

Mitapivat is an investigational, oral, small‐molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3‐DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3‐DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator‐initiated, open‐label study (https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019‐003438‐18), untargeted metabolomics was used to explore the overall metabolic effects of 8‐week treatment with mitapivat in the dose‐finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate‐adjusted p < 0.05), including increases of (derivatives of) polyamines, purines, and acyl carnitines. Eight‐week treatment with mitapivat in nine patients with SCD altered 85/1773 (4.8%) of the total metabolites and 18/139 (12.9%) of the previously identified altered metabolites in SCD (unadjusted p < 0.05). Effects were observed on a broad spectrum of metabolites and were not limited to glycolytic intermediates. Our results show the relevance of metabolic profiling in SCD, not only to unravel potential pathophysiological pathways and biomarkers in multisystem diseases but also to determine the effect of treatment.
Associations of a multiparameter polymerase chain reaction panel on genital samples in mid‐pregnancy with pregnancy outcomes: A prospective cohort study
Authors: Van Praet Jens T. , Engelen Melissa , Lebbe Barbara , Loccufier Anne , Logghe Hilde , Muyldermans Astrid , Hellemans Jorn , Reynders Marijke
Published: June 2024

Synopsis

Results of a multiparameter PCR on genital samples collected in mid‐pregnancy were not associated with pregnancy outcomes.
Detecting emergence of ruptures in individual layers of the stretched intestinal wall using optical coherence elastography: A pilot study
Authors: Kiseleva Elena B. , Sovetsky Alexander A. , Ryabkov Maksim G. , Gubarkova Ekaterina V. , Plekhanov Anton A. , Bederina Evgeniya L. , Potapov Arseniy L. , Bogomolova Alexandra Y. , Zaitsev Vladimir Y. , Gladkova Natalia D.
Published: June 2024

We report a new application of compression optical coherence elastography (C‐OCE) to monitor the emergence of ruptures in individual layers of longitudinally stretched small‐intestine walls using tissue samples (n = 36) from nine minipigs. Before stretching, C‐OCE successfully estimated stiffness for each intestine‐wall layer: longitudinal muscular layer with serosa, circumferential muscular layer, submucosa and mucosa. In stretched samples, C‐OCE clearly visualized initial stiffening in both muscular layers. By 25% elongation, a sharp stiffness decrease for the longitudinal muscular layer, indicated emergence of tears in all samples. With further stretching, for most samples, ruptures emerged in the circumferential muscular layer and submucosa, while mucosa remained undamaged. Histology confirmed the OCE‐revealed damaging and absence of tissue damage for ~15% elongation. Thus, C‐OCE has demonstrated a high potential for determining the safety tissue‐stretching threshold which afterward may be used intraoperatively to prevent rupture risk in intestinal tissues stretched during various diagnostic/therapeutic procedures.
Drug‐Drug Interaction between Oral Zamicastat and Continuous Epoprostenol Infusion at Steady‐State Conditions in Healthy Subjects
Authors: Fonseca Marlene , Guimarães Andreia , Gama Helena , Magalhães Luís , Henriques Sara Carolina , Silva Nuno , Almeida Luis , Soares‐da‐Silva Patrício
Published: June 2024

This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single‐center, open‐label, two‐period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8‐day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat‐to‐epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration–time curve from time 0 up to 16 h at steady state (AUC0‐16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%‐125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0‐τ,ss, the zamicastat plus epoprostenol‐to‐zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0‐τ,ss and the zamicastat plus epoprostenol‐to‐zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0‐τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant.
Test–retest reliability and follow‐up of muscle magnetic resonance elastography in adults with and without muscle diseases
Authors: De Wel Bram , Huysmans Lotte , Peeters Ronald , Ghysels Stefan , Byloos Kris , Putzeys Guido , Maes Frederik , Dupont Patrick , Claeys Kristl G.
Published: June 2024

Background

We investigated the potential of magnetic resonance elastography (MRE) stiffness measurements in skeletal muscles as an outcome measure, by determining its test–retest reliability, as well as its sensitivity to change in a longitudinal follow‐up study.

Methods

We assessed test–retest reliability of muscle MRE in 20 subjects with (n = 5) and without (n = 15) muscle diseases and compared this to Dixon proton density fat fraction (PDFF) and volume measurements. Next, we measured MRE muscle stiffness in 21 adults with Becker muscular dystrophy (BMD) and 21 age‐matched healthy controls at baseline, and after 9 and 18 months. We compared two different methods of analysing MRE data in this study: ‘Method A’ used the stiffness maps generated by the Philips MRE software, and ‘Method B’ applied a custom‐made procedure based on wavelength measurements on the MRE images.

Results

Intraclass correlation coefficients (ICC) of muscle stiffness ranged from good (0.83 for left vastus medialis, P < 0.001) to poor (0.19 for right rectus femoris, P = 0.212) for the examined thigh muscles with Method A, but we did not find a significant test–retest reliability with Method B (P > 0.050 for all). The ICC of muscle PDFF and volume measurements was excellent (>0.90; P < 0.001) for all muscles. At baseline, the average stiffness of all thigh muscles was significantly lower in adults with BMD than in controls for both Method A (−0.2 kPa, P = 0.025) and Method B (−0.6 kPa, P < 0.001). Regardless of which method was used, there was no significant difference in the evolution of muscle stiffness in patients and controls over 18 months.

Conclusions

Test–retest reliability of muscle MRE using a simple 2D technique was suboptimal, and did not reliably measure muscle stiffness changes in adults with BMD as compared with controls over 18 months. While the results provide motivation for testing more advanced 3D MRE methods, we conclude that the simple 2D MRE implementation used in this study is not suitable as an outcome measure for characterizing thigh muscle in clinical trials.
Supplementation with stigma maydis polysaccharide attenuates autism‐like behaviors and improves gut function in valproic acid‐induced autism model male rats
Authors: Yang Xiaolei , Li Hongjie , Yang Chao , Ge Jie
Published: June 2024

Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder (ASD) often experience gastrointestinal problems and dysbiosis in their gut microbiota. Our previous study revealed that SMPS interventions had an impact on the gut microbiota of valproic acid (VPA)‐induced autism model rats. However, the effects of SMPS on the behavior and gut function of autism model rats remain poorly understood. Therefore, we gave different doses of SMPS intervention in the early stage of autism model rats to observe their developmental conditions and behavior performances. Through histological evaluation and real‐time polymerase chain reaction (PCR), integrity of the intestinal structure and the expression of tight junction‐related gene Zo‐1 and Occludin were detected. The results indicated that SMPS intervention improved the physical development, learning and memory impairment, and social performance of autism model rats. Meanwhile, SMPS promoted intestinal peristalsis and restored the integrity of the intestinal structure, reduced the number of inflammatory cells, and increased the expression of the Zo‐1 and Occludin genes. Furthermore, the expression levels of neurotransmitters (substance P, enkephalin, vasoactive intestinal peptide, and 5‐hydroxytryptamine) in the hippocampal tissues were altered after SMPS treatment. In conclusion, SMPS could ameliorate ASD‐like phenotypes and gut problems in autism model rats. Collectively, these results provide new evidence for the relationship between the gut‐brain axis and ASD and suggest a novel therapeutic target for ASD treatment.
Preparation for oxidative stress in Chinese toads (Bufo gargarizans) living under natural conditions along an altitudinal gradient
Authors: Zhang Haiying , Xu Tisen , Jiao Mingxue , Li Xiangyong , Storey Kenneth B. , Niu Yonggang
Published: June 2024

Preparation for oxidative stress (POS) has been widely reported in animals under controlled laboratory conditions, but whether this phenomenon is visible in animals under natural conditions remains to be explored. Altitudinal gradients provide a good opportunity to address this question, since environmental conditions become more hostile with increasing altitude. Here, we investigated the levels of oxidative stress, oxidative damage, and antioxidant defenses in Chinese toads (Bufo gargarizans) along an altitudinal gradient (50 m, 1200 m, 2300 m, 3400 m above sea level). The results show that changing altitude led to a significantly lower ratio of oxidized to reduced glutathione in liver, with a higher value at 50 m. This ratio in muscle tissues did not differ significantly between altitudes of 50 m, 2300 m, and 3400 m. However, reduced glutathione content increased significantly along the altitude, with higher values in liver at 2300 m and higher values in skeletal muscle at 3400 m. Malondialdehyde (MDA) content in liver did not change significantly with increasing altitude. Brain and muscle tissues showed a higher MDA content at 50 m than the other three altitudes. The activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione‐S‐transferase, as well as total antioxidant capacity, also displayed tissue‐specific upregulation in heart, skeletal muscle, and brain, but all of these antioxidant enzymes except for glutathione‐S‐transferase were significantly reduced in liver along the altitudinal gradient. In summary, environmental factors at higher altitude did not lead to higher levels of oxidative stress and oxidative damage in B. gargarizans, mainly due to stronger antioxidant defenses. This study corroborates the occurrence of POS in high‐altitude toads living under field conditions and contributes to revealing the biochemical adaptations to extreme environments at higher altitude.
Professionals' views on providing personalized recurrence risks for de novo mutations: Implications for genetic counseling
Authors: Kay Alison C. , Wells Jonathan , Goriely Anne , Hallowell Nina
Published: June 2024

When an apparent de novo (new) genetic change has been identified as the cause of a serious genetic condition in a child, many couples would like to know the risk of this happening again in a future pregnancy. Current practice provides families with a population average risk of 1%–2%. However, this figure is not accurate for any specific couple, and yet, they are asked to make decisions about having another child and/or whether to have prenatal testing. The PREcision Genetic Counseling And REproduction (PREGCARE) study is a new personalized assessment strategy that refines a couple's recurrence risk prior to a new pregnancy, by analyzing several samples from the parent–child trio (blood, saliva, swabs, and father's sperm) using deep sequencing and haplotyping. Overall, this approach can reassure ~2/3 of couples who have a negligible (<0.1%) recurrence risk and focus support on those at higher risk (i.e. when mosaicism is identified in one of the parents). Here we present a qualitative interview study with UK clinical genetics professionals (n = 20), which investigate the potential implications of introducing such a strategy in genetics clinics. While thematic analysis of the interviews indicated perceived clinical utility, it also indicates a need to prepare couples for the psychosocial implications of parent‐of‐origin information and to support their understanding of the assessment being offered. When dealing with personalized reproductive risk, a traditional non‐directive approach may not meet the needs of practitioner and client(s) and shared decision‐making provides an additional framework that may relieve some patient burden. Further qualitative investigation with couples is planned.
Intervention strategies to improve adherence to treatment for selected chronic conditions in sub‐Saharan Africa: a systematic review
Authors: Gumede Siphamandla Bonga , de Wit John B. F. , Venter Willem D. F. , Wensing Annemarie M. J. , Lalla‐Edward Samanta Tresha
Published: June 2024

Introduction

Evidence‐based intervention strategies to improve adherence among individuals living with chronic conditions are critical in ensuring better outcomes. In this systematic review, we assessed the impact of interventions that aimed to promote adherence to treatment for chronic conditions.

Methods

We systematically searched PubMed, Web of Science, Scopus, Google Scholar and CINAHL databases to identify relevant studies published between the years 2000 and 2023 and used the QUIPS assessment tool to assess the quality and risk of bias of each study. We extracted data from eligible studies for study characteristics and description of interventions for the study populations of interest.

Results

Of the 32,698 total studies/records screened, 2814 were eligible for abstract screening and of those, 497 were eligible for full‐text screening. A total of 82 studies were subsequently included, describing a total of 58,043 patients. Of the total included studies, 58 (70.7%) were related to antiretroviral therapy for HIV, 6 (7.3%) were anti‐hypertensive medication‐related, 12 (14.6%) were anti‐diabetic medication‐related and 6 (7.3%) focused on medication for more than one condition. A total of 54/82 (65.9%) reported improved adherence based on the described study outcomes, 13/82 (15.9%) did not have clear results or defined outcomes, while 15/82 (18.3%) reported no significant difference between studied groups. The 82 publications described 98 unique interventions (some studies described more than one intervention). Among these intervention strategies, 13 (13.3%) were multifaceted (4/13 [30.8%] multi‐component health services‐ and community‐based programmes, 6/13 [46.2%] included individual plus group counselling and 3/13 [23.1%] included SMS or alarm reminders plus individual counselling).

Discussion

The interventions described in this review ranged from adherence counselling to more complex interventions such as mobile health (mhealth) interventions. Combined interventions comprised of different components may be more effective than using a single component in isolation. However, the complexity involved in designing and implementing combined interventions often complicates the practicalities of such interventions.

Conclusions

There is substantial evidence that community‐ and home‐based interventions, digital health interventions and adherence counselling interventions can improve adherence to medication for chronic conditions. Future research should answer if existing interventions can be used to develop less complicated multifaceted adherence intervention strategies.