bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder
Authors: Saleh Hodin Nur Atikah , Chong Siok Geok , Bakar Noraini Abu , Fahmi Muhammad Syafiq Akmal Mohd , Ramlan Nurul Farhana , Hamid Nik Nur Aini Zulaikha Zulkifli , Fadzar Muhammad Syuqor Iqbal Mohd , Zulkifli Abdul Rahman , Norazhar Anis Irfan , Mastuki Siti Nurulhuda , Faudzi Siti Munirah Mohd , Ibrahim Wan Norhamidah Wan , Azmai Mohammad Noor Amal
Published: July 2023

Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety‐like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose‐dependent manner (p ≤ .05). At the selected non‐teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA‐treated fish compared to the control (p ≥ .005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels.
Health‐related quality of life and medication adherence of people living with epilepsy in Pakistan: A cross‐sectional study
Authors: Tanveer Maria , Tahir Azhar Hussain , Iqbal Mansoor , Aslam Faiza , Ahmed Ali
Published: July 2023

Introduction

The primary purpose of this study was to determine adherence and health‐related quality of life (HRQoL) in PWE. Secondary aims were to assess association between adherence and HRQoL and determine predictors of HRQoL in PWE in Pakistan.

Methods

A descriptive cross‐sectional study was conducted among PWE receiving treatment from two tertiary care hospitals of Pakistan. The HRQoL and adherence were assessed with Urdu versions of Quality of Life in Epilepsy‐31 (QOLIE‐31), and Medication Adherence Rating Scale (MARS). Relationship between HRQoL and adherence was assessed by Pearson's product‐moment correlation coefficient. Forced entry multiple linear models were used to determine relationship of independent variables with HRQoL.

Results

219 PWE with a mean (±standard deviation) age, 34.18 (± 13.710) years, participated in this study. The overall weighted mean HRQoL score was (51.60 ± 17.10), and mean score for adherence was 6.17 (± 2.31). There was significant association between adherence and HRQoL in PWE (Pearson's correlation = 0.820–0.930;p ≤ .0001). Multiple linear regression found adherence (B = 16.8;p ≤ .0001), male gender (B = 10.0;p = .001), employment status (employed:B = 7.50;p = .030), level of education (Tertiary:B = 0.910;p = .010), duration of epilepsy (>10 years:B = –0.700;p ≤ .0001), and age (≥46 years:B = –0.680;p ≤ .0001), and ASM therapy (polypharmacy:B = 0.430;p = .010) as independent predictors of HRQoL in PWE from Pakistan.

Conclusions

The findings suggest PWE from our center have suboptimal adherence which affects HRQoL. Independent factors such as male gender, employment status and duration of epilepsy are predictors of HRQoL.
Spanish validation of short‐form version of Literacy of Suicide Scale (LOSS) and Stigma of Suicide Scale (SOSS)
Authors: Collado Fernando , Martínez Julia , Cangas Adolfo J. , Trigueros Rubén
Published: July 2023

Introduction

The evidence shows that a greater understanding of mental health and the myths about suicide is related to a reduction in these types of problems.

Objective

Validate the Literacy of Suicide Scale—Short Form (LOSS‐SF) and the Stigma of Suicide Scale—Short Form (SOSS‐SF) for Spain.

Materials and methods

Both scales were translated to Spanish via backward translation. The sample was comprised of a total of 466 participants, of which 169 (36.2%) were men and 297 (63.6%) were women through nonrandom circumstantial sampling. The questionnaires were administered online. To test the factorial structure and evaluate reliability, both an EFA and an AFC were conducted. In addition, the reliability of the questionnaires was analyzed using the Omega coefficient and Cronbach's alpha. Finally, a linear regression analysis was carried out with the aim of testing the predictability of the scales.

Results and discussion

The results obtained reveal acceptable fit indices and a factorial structure similar to that of the validation conducted for both instruments in other countries. The validity of these instruments for use in Spain is discussed.
Linking business models and digital technologies through integrated reporting
Authors: De Nicola Manuel , Maurizi Anna Maria , Mercuri Francesco , Paolone Francesco
Published: July 2023

Within the 4.0 paradigm, the disruptive adoption of digital technologies is modifying the way companies develop business and manage the relationships within and across their business environment. Although several scholarly contributions have investigated how digital transformation (DT) and business models (BMs) influence each other, a research gap has emerged regarding the relevance attributed to the DT information disclosed in the section of the integrated reports (IRs) devoted to BM. This research investigates the role that reporters attribute to DT by exploring whether and how companies qualify DT as part of their BM and whether it is considered a purely structural factor or a strategic factor able to influence the relationship with stakeholders and the value‐creation process. Based on a content analysis of 48 integrated reports for the years 2020 and 2021, our research insights qualify DT as a driver capable of generating impacts on companies' ecosystems, although the findings do not reveal the adoption of quantitative and forward‐looking information to disclose the relationship between DT and BM. Moreover, our research provides managerial implication in terms of reporting and communication effectiveness, and it is unique and valuable, as it opens up a new line of research on IR and DT.
Blended learning for engineering education 4.0: Students' perceptions and their learning difficulties
Authors: Low Min Chi , Lee Chen Kang , Sidhu Manjit Singh , Lim Seng Poh , Hasan Zaimah , Lim Seng Chee
Published: July 2023

Engineering education plays a vital role in nurturing high‐quality engineers to meet the demands of the industry. The advancement in Information and Communication Technology (ICT) has provided greater potential as a supporting tool in engineering education. Previous research has emphasized the need to further investigate the learning difficulties faced by engineering students to enhance their learning experience. Although the implementation of blended learning using the flipped classroom approach has gained popularity in tertiary education, there is a lack of research on students' perception of this approach in engineering education. This exploratory study focuses on the Engineering domain, specifically investigating students' learning difficulties in Mechanics Dynamics and their attitudes toward blended learning using the flipped classroom approach in engineering education. Using data collected from 121 students at Universiti Tenaga Nasional (UNITEN), Malaysia, this study employed descriptive statistics and multiple linear regression to analyze the data. Three models related to students' learning difficulties were proposed based on the outcomes of exploratory factor analysis. The results indicate that students encountered difficulties in learning Mechanics Dynamics, particularly in visualizing concepts and solving problems involving three dimensions. The findings and analysis demonstrate significant results (p < .05), supporting the hypotheses of the three proposed models. Additionally, the majority of students (66.1%) exhibited a positive attitude toward the use of the flipped classroom approach in engineering courses. The research findings serve as a preliminary requirement for the development of a software prototype to investigate the efficacy of the flipped classroom approach in engineering courses.
Parazoanthus axinellae Extract Incorporated Hybrid Nanostructure and Its Potential Antimicrobial Activity**
Authors: Konuklugil Belma , Uras Ibrahim Seyda , Karsli Baris , Demirbas Ayse
Published: July 2023

This study, it was aimed to examine the change in the antimicrobial effect of sea anemone Parazoanthus axinellae extract by forming its nanoflowers. A scanning electron microscope (SEM) and energy dispersive X‐ray spectroscopy (EDX) were expended to observe the morphologies of the Cu NFs that had been produced. Fourier transform infrared spectroscopy (FT‐IR) and X‐ray diffraction (XRD) techniques were expended to analyze the managing assemblies in P. axinellae extract, which perform an effective part in the synthesis routine, as well as the crystal assembly of NFs.

P. axinellae extract mediated the HNFs (Hybrid nanoflowers) are at high, pure crystalline nature, flower shape with a crystallographic system at the nanoscale with mean crystallite size 21.9 nm using XRD, and average particle size ~10 nm by SEM. The broad absorption band at 2981–2915 cm−1 in the FT‐IR spectra of anemone extract and Cu‐anemone NFs represents the unique peak of hydroxy groups.

In addition, Cu NFs were tested for their antibacterial properties. Cu NFs have been discovered to exhibit antibacterial properties. It is suggested that P. axinellae extract and various inorganic components be used to synthesize a variety of NFs and assess their suitability for usage in biomedical fields.
Lycopodium Alkaloids from Huperzia serrata and Their Anti‐acetylcholinesterase Activities
Authors: Li Wen , Zhu Hui‐Hui , Shen Xi , Tan Jin‐Lin , Tang Qing , Ling Zhi‐Peng , Zhao Hai‐Yue , Lin Qiang , Sun Hui , Zhang Hai‐Peng , Li Yao‐Lan , Wang Guo‐Cai , Zhang Yu‐Bo
Published: July 2023

One new fawcettimine‐type alkaloid (1), one new miscellaneous‐type alkaloid (2), four new lycodine‐type alkaloids (3–6), and eight known ones (7–14) were isolated from the whole plants of Huperzia serrata. Their structures and absolute configurations were elucidated based on spectroscopic data, X‐ray diffraction, ECD calculation and Mosher's method. Compound 1 was a rare C18N2‐type Lycopodium alkaloid, possessing serratinine skeleton with an amide side chain in C‐5. The absolute configuration of the 18‐OH of compounds 4–6 were first determined by Mosher's method. Moreover, compounds 1–14 were assayed anti‐acetylcholinesterase effect in vitro, and compound 7 showed significant anti‐acetylcholinesterase activity with an IC50 value of 16.18±1.64 μM.
Spatially Resolved Chiroptical Spectroscopies Emphasizing Recent Applications to Thin Films of Chiral Organic Dyes
Authors: Albano Gianluigi , Taddeucci Andrea , Pescitelli Gennaro , Di Bari Lorenzo
Published: July 2023

Instrumental techniques able to identify and structurally characterize the aggregation states in thin films of chiral organic π‐conjugated materials, from the first‐order supramolecular arrangement up to the microscopic and mesoscopic scale, are very helpful for clarifying structure‐property relationships. Chiroptical imaging is currently gaining a central role, for its ability of mapping local supramolecular structures in thin films. The present review gives an overview of electronic circular dichroism imaging (ECDi), circularly polarized luminescence imaging (CPLi), and vibrational circular dichroism imaging (VCDi), with a focus on their applications on thin films of chiral organic dyes as case studies.
Visible‐Light Enabled Dehydroxylative Alkylation of α‐Hydroxy Carboxylic Acid Derivatives via C−O Bond Cleavage
Authors: Liu Xiaobo , Lu Minming , Guo Xiangli , Xu Huajian , Xu Jun
Published: July 2023

A novel visible‐light photoredox strategy is reported for the efficient dehydroxylative alkylation of a wide array of α‐hydroxy carboxylic acid derivatives using diaryl boron radical. The reaction features readily accessible starting materials, broad substrate scope with excellent functionality tolerance. Preliminary mechanistic studies reveal that the spin‐center shift process is responsible for the C−O bond activation, which is promoted by the diaryl boron radical generated from bench‐stable and commercially available tetraphenyl borate (NaBPh4).
Electronic Structure Modulation of Nanographenes for Second Order Nonlinear Optical Molecular Materials
Authors: Yang Cui‐Cui , Tian Wei Quan
Published: July 2023

Nanographenes (NGs) have drawn extensive attention as promising candidates for next‐generation optoelectronic and nonlinear optical (NLO) materials, owing to its unique optoelectronic properties and high thermal stability. However, the weak polarity or even non‐polarity of NGs (resulting in weak even order NLO properties) and the high chemical reactivity of zigzag edged NGs hinder their further applications in nonlinear optics, thus stabilization (lowering the chemical reactivity) and polarizing the charge distribution in NGs are necessary for such applications of NGs. The fusion of heptagon and pentagon endows the azulene with the character of donor‐acceptor, and the B=N unit is isoelectronic to C=C unit. The introduction of polar azulene and BN are idea to polarize and stabilize the electronic structure of NGs for NLO applications. In the present review, a survey on the functionalization and applications of NGs in nonlinear optics is conducted. The engineering of the electronic structure of NGs by topological defects, doping and edge modulation is summarized. Finally, a summary of challenges and perspectives for carbon‐based NLO nanomaterials is presented.
Research progress in water‐saving cultivation of rice in China
Authors: Jiang Hao , Xing Xu , Meng Xin , Chen Junlei , Yu Kuo , Xu Xiaotian , Zhang Rui , Wei Zhiheng , Wang Dongchao , Cang Baifeng , Bai Chenyang , Li Yunzhe , Jiang Zixian , Wei Xiaoshuang , Tian Ping , Yang Meiying , Wu Zhihai
Published: July 2023

The conflict between rice production and water scarcity is becoming more pronounced. Therefore, the advancement of water‐saving rice cultivation is crucial in guaranteeing both food and ecological security. This study provides a summary of the development and characteristics of various water‐saving cultivation techniques for rice, including alternate wetting and drying irrigation, wet irrigation, controlled irrigation, the system of rice intensification, direct seeding rice, and dry cultivation of rice (DCR). We also introduce the varietal characteristics of upland rice, aerobic rice, water‐saving and drought‐resistant rice, and DCR. We summarize the impact of different water‐saving cultivation models on yield and quality and regulatory measures, and propose challenges and strategies for the development of water‐saving cultivation of rice in the future. We hope to provide a reference for promoting the development of rice water‐saving cultivation and dry farming agriculture.
Course and outcome in individuals with atypical anorexia nervosa: Findings from the Study of Refeeding to Optimize iNpatient Gains (StRONG)
Authors: Golden Neville H. , Kapphahn Cynthia J. , Cheng Jing , Kreiter Anna , Downey Amanda E. , Accurso Erin C. , Machen Vanessa I. , Adams Sally H. , Buckelew Sara M. , Moscicki Anna‐Barbara , Le Grange Daniel , Garber Andrea K.
Published: July 2023

Objective

We previously reported that participants with atypical anorexia nervosa (atypical AN) had higher historical and admission weights, greater eating disorder psychopathology, but similar rates of amenorrhea and weight suppression at baseline as compared to anorexia nervosa (AN); here, we compare 1‐year outcomes.

Method

Weight, % median body mass index (%mBMI), Eating Disorder Examination Questionnaire (EDE‐Q) scores, resumption of menses, and rehospitalizations were examined at 3, 6, and 12 months post‐discharge. Analyses (N = 111) compared changes in %mBMI, weight suppression, and EDE‐Q scores over time between atypical AN and AN.

Results

Among the participants (48 atypical AN, 63 AN), both groups gained weight but those with atypical AN had lower gains than those with AN in %mBMI (p = .02) and greater weight suppression (p = .002) over time. EDE‐Q scores improved over time, independent of weight suppression, with no significant difference between atypical AN and AN. Groups did not differ by rates of resumption of menses (80% atypical AN, 76.9% AN) or rehospitalization (29.2% atypical AN, 37.9% AN). Greater weight suppression predicted longer time to restore menses and more days of rehospitalization.

Discussion

Individuals with atypical AN regained a smaller proportion of body mass and were more weight suppressed over time. Change in eating disorder cognitions, resumption of menses, and rehospitalization rates at 1‐year follow‐up did not differ between groups. There was no significant difference in weight suppression between groups for those who were psychologically improved at 12 months. Findings highlight limitations in our understanding of weight recovery in atypical AN. New metrics for recovery are urgently needed.

Public Significance

Little is known about outcome in atypical anorexia nervosa (atypical AN). We examined recovery metrics in young people with atypical AN and anorexia nervosa (AN) 1 year after medical hospitalization. Individuals with atypical AN showed slower weight gain and remained further from their pre‐illness weight. There were no differences in the rates of psychological recovery, resumption of menses, or rehospitalization. New metrics are needed to assess recovery in atypical AN.
Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct‐acting antivirals
Authors: Bi Wenjie , Kraft Anke , Engelskircher Sophie , Mischke Jasmin , Witte Moana , Klawonn Frank , van Ham Marco , Cornberg Markus , Wedemeyer Heiner , Hengst Julia , Jänsch Lothar
Published: July 2023

Chronic hepatitis C virus (HCV) infections compromise natural killer (NK)‐cell immunity. Direct‐acting antivirals (DAA) effectively eliminate HCV, but the long‐term effects on NK cells in cured patients are debated. We conducted a proteomic study on CD56+ NK cells of chronic HCV‐infected patients before and 1 year after DAA therapy. Donor‐variation was observed in NK‐cell proteomes of HCV‐infected patients, with 46 dysregulated proteins restored after DAA therapy. However, 30% of the CD56+ NK‐cell proteome remained altered 1 year post‐therapy, indicating a phenotypic shift with low donor‐variation. NK cells from virus‐negative cured patients exhibited global regulation of RNA‐processing and pathways related to “stimuli response”, “chemokine signaling”, and “cytotoxicity regulation”. Proteomics identified downregulation of vesicle transport components (CD107a, COPI/II complexes) and altered receptor expression profiles, indicating an inhibited NK‐cell phenotype. Yet, activated NK cells from HCV patients before and after therapy effectively upregulated IFN‐γ and recruited CD107a. Conversely, reduced surface expression levels of Tim‐3 and 2B4 were observed before and after therapy. In conclusion, this study reveals long‐term effects on the CD56+ NK‐cell compartment in convalescent HCV patients 1 year after therapy, with limited abundance of vesicle transport complexes and surface receptors, associated with a responsive NK‐cell phenotype.
Quantifying the Electronic Effect of C4 and C4′ Positions of Bipyridine Ligand on Pd(II)/Rh(I)‐Catalyzed Conjugate Addition Reaction: A DFT Study
Authors: Jie Yao , Zhang Wei , Guo Jing‐Yi , Lu Hao , Song Hui‐Ting , Xu Xin‐Yu , Yan Hong
Published: July 2023

The electronic effects of the bidentate ligands play a vital role in the transition metal‐catalyzed conjugate addition reactions. Here, the insertion step (rate‐determining step (RDS) of the conjugate addition) catalyzed by Pd(II)/Rh(I)‐complexes with 26 bipyridine‐type (bpy) ligands linking different substituent groups in the opposite sides (C4, C4′ position) are systematically studied by density functional theory (DFT). It is found that for both Pd(II)‐ and Rh(I)‐catalysis, the stronger the electron‐withdrawing group connecting to both C4 and C4′ positions of bpy ligands can promote the insertion step. The predominance of π‐back donation in Rh(I) and σ‐donation in Pd(II) is the main reason for above different electronic properties of Pd(II) and Rh(I)‐catalysis. This work gives enough theoretical guide to the rational design of the efficient transition metal‐based catalyst for conjugate addition.
First description of lingual focal motor status epilepticus due to acute ischemic stroke
Authors: Nucera Bruna , Rinaldi Fabrizio , Flore Davide , Panebianco Luca , Bratti Arianna , Ferraiuolo Imma , Nardone Raffaele , Brigo Francesco
Published: July 2023

Content available: Video.
MYT1L variant inherited by a mosaic father in a case of severe developmental and epileptic encephalopathy
Authors: Boeri Silvia , Scala Marcello , Madia Francesca , Perucco Francesca , Vozzi Diego , Capra Valeria , Zara Federico , Nobili Lino , Mancardi Maria Margherita
Published: July 2023

The MYT1L gene plays a critical role in brain development, promoting the differentiation and proliferation of cells, important for the formation of brain connections. MYT1L is also involved in regulating the development of the hypothalamus, which is a crucial actor in weight regulation. Genetic variants in the MYT1L are associated with a range of developmental disorders, including intellectual disability, autism spectrum disorder, facial dysmorphisms, and epilepsy. The specific role of MYT1L in epilepsy remains elusive and no patients with developmental and epileptic encephalopathy (DEE) have been described so far. In this study, we report a patient with DEE presenting with severe refractory epilepsy, obesity, and behavioral abnormalities. Exome sequencing led to the identification of the heterozygous variant NM_001303052.2: c.1717G>A, p.(Gly573Arg) (chr2‐1910340‐C‐T; GRCh38.p14) in the MYT1L gene. This variant was found to be inherited by the father, who was a mosaic and did not suffer from any neuropsychiatric disorders. Our observations expand the molecular and phenotype spectrum of MYT1L‐related disorders, suggesting that affected individuals may present with severe epileptic phenotype leading to neurocognitive deterioration. Furthermore, we show that mosaic parents may not display the disease phenotype, with relevant implications for genetic counseling.
Protein biomarker for early diagnosis of microbial toxin contamination: Using Aspergillus flavus as an example
Authors: Fu Jiayun , Gu Mei , Yan Honglin , Zhang Minhui , Xie Huali , Yue Xiaofeng , Zhang Qi , Li Peiwu
Published: July 2023

Microbial toxins are important factors that contribute to human diseases and food losses. Predicting the production of these toxins before they occur is a significant challenge. In this study, we innovatively developed a strategy called targeted acquisition of toxin‐related immunogen (TATRI) to identify early diagnostic biomarkers for microbial toxins. Taking Aspergillus flavus as an example, we employed an immunoassay‐based screening approach to identify nanobodies that exhibited significant response signals to different toxigenic strains. Subsequently, we isolated and purified the specific immunogen pre‐aflatoxin biomarker PAB‐01 that bound to the selected nanobody. The results showed that the level of PAB‐01 was positively correlated with the toxin‐producing ability of A. flavus strains and could be detected before the production of aflatoxins. It met the essential requirements as an early diagnostic biomarker for aflatoxin contamination. Protein identification and bioinformatics analysis revealed that PAB‐01 is a glycoprotein that can be secreted into the extracellular space. It is located on chromosome 5 of A. flavus and belongs to the 75 family of glycoside hydrolases. Furthermore, we used 7 g/kg as the critical concentration of PAB‐01 to diagnose the risk of aflatoxin contamination in stored peanuts, with an accuracy rate of 75.9% for high‐risk samples. In summary, this work provides a promising approach for the identification of protein biomarkers prior to microbial toxin production and the establishment of early diagnostic techniques for microbial toxins.
Investigation of the effects of different processing methods on the selected nutritional properties of pumpkin and determining the appropriate process for pumpkin yogurt
Authors: Sıçramaz Hatice , Ayar Ahmet
Published: July 2023

The processing methods, especially cooking, can cause quality losses, particularly in the nutritional value of the fresh product. This study investigated the effects of preprocessing methods on the nutritional properties of pumpkin and the physicochemical and sensory properties of pumpkin yogurt. Two different pumpkin varieties (Cucurbita pepo and Cucurbita maxima) were subjected to three different preprocessing methods (freeze‐drying, boiling, and baking). Boiling significantly increased antioxidant activity (p ≤ .05), followed by baking. C. maxima had higher TDF and TPC than C. pepo, but in both pumpkin varieties, TDF did not change with heat treatment (boiling and baking), while TPC decreased. Mineral contents remained the same or decreased with heat treatment, except for Mn and Fe. In particular, the addition of C. maxima significantly affected the color parameters (L*, a*, b*) of yogurt and improved WHC (from 68.9% to 91.6%) and hardness (from 58.0 to 193.5 g; p ≤ .05). The sensory evaluation concluded that heat‐treated (boiled and baked) samples were preferred more than freeze‐dried raw ones. In conclusion, the results revealed that adding boiled and baked pumpkins, especially the preference for C. maxima instead of C. pepo, improved the quality parameters of yogurt.
Altered dynamic brain activity and functional connectivity in thyroid‐associated ophthalmopathy
Authors: Jiang Wen‐Hao , Liu Jun , Zhou Jiang , Wu Qian , Pu Xiong‐Ying , Chen Huan‐Huan , Xu Xiao‐Quan , Wu Fei‐Yun , Hu Hao
Published: July 2023

Although previous neuroimaging evidence has confirmed the brain functional disturbances in thyroid‐associated ophthalmopathy (TAO), the dynamic characteristics of brain activity and functional connectivity (FC) in TAO were rarely concerned. The present study aims to investigate the alterations of temporal variability of brain activity and FC in TAO using resting‐state functional magnetic resonance imaging (rs‐fMRI). Forty‐seven TAO patients and 30 age‐, gender‐, education‐, and handedness‐matched healthy controls (HCs) were enrolled and underwent rs‐fMRI scanning. The dynamic amplitude of low‐frequency fluctuation (dALFF) was first calculated using a sliding window approach to characterize the temporal variability of brain activity. Based on the dALFF results, seed‐based dynamic functional connectivity (dFC) analysis was performed to identify the temporal variability of efficient communication between brain regions in TAO. Additionally, correlations between dALFF and dFC and the clinical indicators were analyzed. Compared with HCs, TAO patients displayed decreased dALFF in the left superior occipital gyrus (SOG) and cuneus (CUN), while showing increased dALFF in the left triangular part of inferior frontal gyrus (IFGtriang), insula (INS), orbital part of inferior frontal gyrus (ORBinf), superior temporal gyrus (STG) and temporal pole of superior temporal gyrus (TPOsup). Furthermore, TAO patients exhibited decreased dFC between the left STG and the right middle occipital gyrus (MOG), as well as decreased dFC between the left TPOsup and the right calcarine fissure and surrounding cortex (CAL) and MOG. Correlation analyses showed that the altered dALFF in the left SOG/CUN was positively related to visual acuity (r = .409, p = .004), as well as the score of QoL for visual functioning (r = .375, p = .009). TAO patients developed abnormal temporal variability of brain activity in areas related to vision, emotion, and cognition, as well as reduced temporal variability of FC associated with vision deficits. These findings provided additional insights into the neurobiological mechanisms of TAO.
Financial issues in times of a COVID‐19 pandemic in a tertiary hospital in Mali
Authors: Ridde Valéry , Coulibaly Abdourahmane , Touré Laurence , Ba Mouhamadou Faly , Zinszer Kate , Bonnet Emmanuel , Honda Ayako
Published: July 2023

Background

This study examines how the functioning of healthcare providers during the COVID‐19 pandemic was affected by the government financing response, which was shaped by existing healthcare financing systems.

Methods

The study applied a single case study design at a tertiary hospital in Bamako during the 1st and 2nd waves of the COVID‐19 pandemic. Data were gathered through 51 in‐depth interviews with hospital staff, participatory observation, and reviewing media articles and hospital financial records.

Results

The study revealed the disruptions experienced by hospital managers, human resources for health and patients in Mali during the early stages of the pandemic. While the government aimed to support universal access to COVID‐19‐related services, efforts were undermined by issues associated with complex public financing management procedures. The hospital experienced long delays in transferring government funds. The hospital suffered a decrease in revenue during the early stages of the pandemic. Government budgets were not effectively used because of complex, non‐agile procedures that could not adapt to the emergency. The challenges faced by the hospitals led to the delays in the staff payments of salaries and promised bonuses, which created potential for unfair treatment of patients. Excluding some COVID‐19 related items from the government funded benefit package created a financial burden on people receiving services. The managerial challenges experienced in the study hospital during the first wave continued in the second wave.

Conclusions

Pre‐existent issues in healthcare financing and governance constrained the effective management of COVID‐19‐related services and created confusion at the front line of healthcare service delivery.
Global research publications on cardiovascular and pulmonary rehabilitation and their alignment with population rehabilitation needs: An ecological study
Authors: Reboredo Maycon Moura , Erothildes Ferreira Renato , Bainha Ana Clara Cattete , Correia Tiago , Jesus Tiago S.
Published: July 2023

Purpose

Towards informing health research policy and planning, this article evaluates the relationship of the research publications in cardiac rehabilitation (CR) and pulmonary rehabilitation (PR) with the rehabilitation needs arising from cardiovascular diseases (except stroke) and chronic respiratory diseases, over time (1990–2017).

Methods

Ecological study using a secondary analysis and linear regressions of public domain data to associate two datasets of population‐level data: (1) research publications for CR and PR (data from the PubMed database); and (2) global need for CR and PR (data from the Global Burden of Disease study).

Results

The percentage of both CR and PR publications (among total rehabilitation research) significantly decreased from 1990 to 2017 (both: p < 0.01). PR needs and research publications were aligned: around 5% of total rehabilitation needs and rehabilitation research. For CR needs (around 2%, but significantly increasing since 1990), we found a greater portion of CR research publications (6.5% or over). Finally, we found an inverse association among the percentage of CR research publications and CR needs (b = −6.08; r2 = 0.37, p = 0.001).

Conclusion

The portion of CR and PR research (among total rehabilitation research) is declining over time. Yearly percentage of CR publications were greater than those of PR but for lower level of rehabilitation need, but the disparate trend was significantly decreasing over time. Population rehabilitation needs and their alignment with research volume must be one factor in the design of population‐centred, equitable health research priorities.
Cynical hostility increases whereas sense of coherence decreases the odds for current suicidal thoughts: A cross‐sectional study of the general adult population sample
Authors: Palmu Raimo , Partonen Timo
Published: July 2023

Background and Aims

Earlier, somatic diseases and mental disorders have been associated with cynical hostility as well as sense of coherence, but there is a gap of knowledge, whether they contribute to suicidality at population level.

Methods

A random sample of adults, representative of the general population living in Finland, participated in a nationwide health examination study. For 4387 participants aged 18–97 years, we analyzed, after controlling for confounding factors, whether cynical hostility, as assessed with the 8‐item Cook‐Medley Hostility Scale, or sense of coherence, as assessed with the 13‐item Sense of Coherence Scale, contributed to current suicidal thoughts during the past 7 days as scored on the 25‐item Hopkins Symptom Checklist.

Results

Suicidal thoughts (current thoughts of ending one's life) were associated significantly with cynical hostility (p < 0.001) as well as with sense of coherence (p < 0.001). Of the specific items of cynical hostility, the item “I am sure that most people do not have problems with lying for their own good” was associated most strongly with current suicidal thoughts (p < 0.001).

Conclusion

Cynical hostility predicted current suicidal thoughts in a population‐based sample of adults aged 18–97 years. Sense of coherence protected from current suicidal thoughts.
Optimization of machine learning classification models for tumor cells based on cell elements heterogeneity with laser‐induced breakdown spectroscopy
Authors: Wang Yimeng , Huang Da , Shu Kaiqiang , Xu Yingtong , Duan Yixiang , Fan Qingwen , Lin Qingyu , Tuchin Valery V.
Published: July 2023

The rapid and accurate diagnosis of cancer is an important topic in clinical medicine. In the present work, an innovative method based on laser‐induced breakdown spectroscopy (LIBS) combined with machine learning was developed to distinguish and classify different tumor cell lines. The LIBS spectra of cells were first acquired. Then the spectral pre‐processing was performed as well as detailed optimization to improve the classification accuracy. After that, the convolutional neural network (CNN), support vector machine (SVM), and K‐nearest neighbors were further compared for the optimized classification ability of tumor cells. Both the CNN algorithm and SVM algorithm have achieved impressive discrimination performances for tumor cells distinguishing, with an accuracy of 97.72%. The results show that the heterogeneity of elements in tumor cells plays an important role in distinguishing the cells. It also means that the LIBS technique can be used as a fast classification method for classifying tumor cells.
A Novel RUNX1 Genetic Variant Identified in a Young Male with Severe Osteoporosis
Authors: Block Tomasz J. , Shore‐Lorenti Cat , Zebaze Roger , Kerr Peter G. , Kalff Anna , Perkins Andrew Charles , Ebeling Peter R. , Milat Frances
Published: July 2023

This case describes a young man with an unusual cause of severe osteoporosis and markedly deranged bone microarchitecture resulting in multiple fractures. A potentially pathogenic germline variant in the runt‐related transcription factor 1 (RUNX1) gene was discovered by a focused 51‐gene myeloid malignancy panel during investigation for his unexplained normochromic normocytic anemia. Further bone‐specific genetic testing and a pedigree analysis were declined by the patient. Recent experimental evidence demonstrates that RUNX1 plays a key role in the regulation of osteogenesis and bone homeostasis during skeletal development, mediated by the bone morphogenic protein and Wnt signaling pathways. Therefore, rarer causes of osteoporosis, including those affecting bone formation, should be considered in young patients with multiple unexpected minimal trauma fractures. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Evaluation of Truncated AUC as an Alternative Measure to Assess Pharmacokinetic Comparability in Bridging Biologic–Device Using Prefilled Syringes and Autoinjectors
Authors: Wen Ya‐Feng , Ji Ping , Schrieber Sarah J. , Rathi Sneha , McGuirt Delaney , Liu Jiang , Chen Jianmeng , Wang Yow‐Ming , Doddapaneni Suresh , Sahajwalla Chandrahas
Published: July 2023

Pharmacokinetic (PK) comparisons between therapeutic biologics have largely been based on the total area under the concentration–time curve (AUC) and the maximum concentration (Cmax). For biologics with a long half‐life, a PK comparability study may be long in duration and costly to conduct. The goal of this study was to evaluate whether a truncated AUC (tAUC) can be used to assess PK comparability when bridging prefilled syringe (PFS) and autoinjector (AI) treatment options for biologics with a long half‐life. Fifteen biologics license applications (BLAs) were included to determine the concordance and geometric percent coefficient of variation (%CV) between tAUCs evaluated on days 7, 14, 21, and 28 and AUC evaluated to infinity (AUC0–inf). Concordance is established if the tAUCs are comparable with AUC0–inf. Trial simulation was performed to examine the effect of the absorption rate constant (ka) and sample size on the concordance of tAUCs. The tAUCs evaluated on day 14, 21, and 28 had 100% concordance with AUC0–inf for all 15 BLAs. The concordance of tAUC evaluated at day 7 was 87.5%. Based on the trial simulation, tAUC evaluated to day 28 post‐dose can achieve high concordance (≥85%) for biologics exhibiting linear or nonlinear elimination with a ka of ≥0.1/day and with a sample size of 70 subjects per arm. tAUC appears to be a promising alternative PK measure, relative to AUC0–inf, for PK comparability assessments.
Short‐ and Long‐Term MRI Assessed Hemodynamic Changes in Pediatric Moyamoya Patients After Revascularization
Authors: Zhao Moss Y. , Tong Elizabeth , Duarte Armindo Rui , Fettahoglu Ates , Choi Jason , Bagley Jacob , Yeom Kristen W. , Moseley Michael , Steinberg Gary K. , Zaharchuk Greg
Published: July 2023

Background

Cerebrovascular reserve (CVR) reflects the capacity of cerebral blood flow (CBF) to change following a vasodilation challenge. Decreased CVR is associated with a higher stroke risk in patients with cerebrovascular diseases. While revascularization can improve CVR and reduce this risk in adult patients with vasculopathy such as those with Moyamoya disease, its impact on hemodynamics in pediatric patients remains to be elucidated. Arterial spin labeling (ASL) is a quantitative MRI technique that can measure CBF, CVR, and arterial transit time (ATT) non‐invasively.

Purpose

To investigate the short‐ and long‐term changes in hemodynamics after bypass surgeries in patients with Moyamoya disease.

Study Type

Longitudinal.

Population

Forty‐six patients (11 months–18 years, 28 females) with Moyamoya disease.

Field Strength/Sequence

3‐T, single‐ and multi‐delay ASL, T1‐weighted, T2‐FLAIR, 3D MRA.

Assessment

Imaging was performed 2 weeks before and 1 week and 6 months after surgical intervention. Acetazolamide was employed to induce vasodilation during the imaging procedure. CBF and ATT were measured by fitting the ASL data to the general kinetic model. CVR was computed as the percentage change in CBF. The mean CBF, ATT, and CVR values were measured in the regions affected by vasculopathy.

Statistical Tests

Pre‐ and post‐revascularization CVR, CBF, and ATT were compared for different regions of the brain. P‐values <0.05 were considered statistically significant.

Results

ASL‐derived CBF in flow territories affected by vasculopathy significantly increased after bypass by 41 ± 31% within a week. At 6 months, CBF significantly increased by 51 ± 34%, CVR increased by 68 ± 33%, and ATT was significantly reduced by 6.6 ± 2.9%.

Data Conclusion

There may be short‐ and long‐term improvement in the hemodynamic parameters of pediatric Moyamoya patients after bypass surgery.

Evidence Level

4

Technical Efficacy

Stage 2
Detection of Dolichoectasia and Atherosclerosis by Automated MRA Tortuosity Metrics in a Population‐Based Study
Authors: Zhou Shang , Qiao Ye , Zhou Xinwei , Wasserman Bruce A. , Caughey Melissa C.
Published: July 2023

Background

Intracranial vessel tortuosity is a key component of dolichoectasia and has been associated with atherosclerosis and adverse neurologic outcomes. However, the evaluation of tortuosity is mainly a descriptive assessment.

Purpose

To compare the performance of three automated tortuosity metrics (angle metric [AM], distance metric [DM], and distance‐to‐axis metric [DTA]) for detection of dolichoectasia and presence of segment‐specific plaques.

Study Type

Observational, cross‐sectional metric assessment.

Population

1899 adults from the general population; mean age = 76 years, female = 59%, and black = 29%.

Field Strength/Sequence

3‐T, three‐dimensional (3D) time‐of‐flight MRA and 3D vessel wall MRI.

Assessment

Tortuosity metrics and mean luminal area were quantified for designated segments of the internal carotid artery, middle cerebral artery, anterior cerebral artery, posterior cerebral artery, vertebral artery, and entire length of basilar artery (BA). Qualitative interpretations of BA dolichoectasia were assessed based on Smoker's visual criteria.

Statistical Tests

Descriptive statistics (2‐sample t‐tests, Pearson chi‐square tests) for group comparisons. Receiver operating characteristics area under the curve (AUC) for detection of BA dolichoectasia or segment‐specific plaque. Model inputs included 1) tortuosity metrics, 2) mean luminal area, and 3) demographics (age, race, and sex).

Results

Qualitative dolichoectasia was identified in 336 (18%) participants, and atherosclerotic plaques were detected in 192 (10%) participants. AM‐, DM‐, and DTA‐calculated tortuosity were good individual discriminators of basilar dolichoectasia (AUCs: 0.76, 0.74, and 0.75, respectively), with model performance improving with the mean lumen area: (AUCs: 0.88, 0.87, and 0.87, respectively). Combined characteristics (tortuosity and mean luminal area) identified plaques with better performance in the anterior (AUCs ranging from 0.66 to 0.78) than posterior (AUCs ranging from 0.54 to 0.65) circulation, with all models improving by the addition of demographics (AUCs ranging from 0.62 to 0.84).

Data Conclusion

Quantitative vessel tortuosity metrics yield good diagnostic accuracy for the detection of dolichoectasia.

Level of Evidence

1

Technical Efficacy Stage

2
Significance of Arterial Spin Labeling for Reducing Biopsies in Patients With Kidney Allograft Dysfunction
Authors: Wang Wei , Yu Yuanmeng , Li Xue , Chen Jinsong , Zhang Longjiang , Wen Jiqiu
Published: July 2023

Background

Although biopsy is often entailed for managing patients with kidney allograft dysfunction, it is associated with potential complications of severe hemorrhage. Arterial spin labeling (ASL) is a non‐invasive technique that assesses tissue perfusion.

Purpose

To assess the utility of ASL for the discrimination of patients with post‐transplant allograft dysfunction who do not need biopsy from those who need.

Study Type

Prospective.

Subjects

Forty‐six patients (34 males/12 females, aged 38.8 ± 9.5 years) with kidney allograft dysfunction, including 31 in which biopsy directly lead to changes in management (NECESSARY group) and 15 in which clinical management did not alter after biopsy (UNNECESSARY group).

Field Strength/Sequence

3.0 T and 3D fast‐spin echo sequence.

Assessment

All patients underwent both ASL scan and biopsies. The serum creatinine, proteinuria, pathologic results, and cortical ASL readings were obtained and compared between the two groups.

Statistical Analyses

Chi‐square test, independent student t‐test, Mann–Whitney U test, receiver‐operating characteristic curve. A two‐tailed P < 0.05 denoted statistical significance.

Results

The NECESSARY group presented with significantly elevated serum creatinine as compared with the UNNECESSARY group (1.87 ± 0.56 mg/dL vs. 1.31 ± 0.37 mg/dL). The acute composite score was significantly higher in the NECESSARY group than that in the UNNECESSARY group (7 [4–8] vs. 1 [0–2]). Cortical ASL in the NECESSARY group was significantly decreased as compared with the UNNECESSARY group (108.06 [69.96–134.92] mL/min/100 g vs. 153.48 [113.19–160.37] mL/min/100 g). Serum creatinine differentiated UNNCESSARY group from the NECESSARY group with an area under the curve (AUC) and specificity of 0.79 and 54.84%, respectively. By comparison, the cortical ASL yielded an AUC of 0.75 and a specificity of 70.97%. Notably, the specificity was increased to 90.30% by combined use of serum creatinine and cortical ASL.

Data Conclusion

The combined use of ASL and serum creatinine yielded a high specificity for selecting patients who may not need allograft biopsy.

Level of Evidence

2

Technical Efficacy

Stage 3
Rotavirus vaccination as a public health strategy to reduce the burden of hospitalization: The field experience of Italy (2008−2018)
Authors: Amodio Emanuele , D'Anna Antonio , Verso Maria G. , Leonforte Francesco , Genovese Dario , Vitale Francesco
Published: July 2023

Rotavirus (RV) infection is a leading cause of severe diarrhea among children younger than 5 years old and a considerable cause of RV gastroenteritis (RVGE) hospitalization. This study aimed to evaluate the impact of vaccination in Italy in the reduction of the burden of RV‐related disease, estimating the relation between vaccination coverage and hospitalization rates. RVGE‐related hospitalizations that occurred in Italy from 2008 to 2018 among children aged 0−35 months were assessed by consulting the Hospital Discharge Record database and including records whose ICD‐9‐CM diagnosis code was 008.61 in the first or in any diagnosis position. In the 2008−2018 period, a total of 17 535 791 at‐risk person‐years were considered and 74 211 (423.2 cases × 100 000 per year) RVGE hospitalizations were observed. Higher hospitalization rates occurred in males (456.6 vs. 387.9 × 100 000 per year) and in children aged 1 year (507.8 × 100 000 per year). Poisson regression analysis showed a decrease of −1.25% in hospitalization rates (−1.19% to −1.31%, p < 0.001) per unit increase in vaccination coverage. This is the first study that correlates hospitalization rate reduction with a percentage increase in vaccination coverage. Our findings strongly support RV vaccination as an effective public health strategy for reducing RVGE‐related hospitalizations.
The state of motivational interviewing training in school counseling graduate programs
Authors: North Reagan , Pincus Robert
Published: July 2023

Motivational interviewing (MI) is a brief, evidence‐based counseling style that helps people make positive behavior changes. Scholars have advocated for MI's use by school counselors (SCs), and research lends evidence to MI's effectiveness in schools. However, there are little data focused on how SCs are trained to utilize MI. Researchers investigated MI training in school counseling graduate programs from the perspective of SCs and counselor educators (CEs). The article presents two qualitative studies that discussed the importance of MI training in graduate programs. Researchers identified six themes and discussed their implications for graduate programs.