bluuebunny/crossref_metadata_2025 huggingface dataset:
A new one‐stop interdisciplinary cognitive clinic model tackles rural health inequality and halves the time to diagnosis: Benchmarked against a national dementia registry
Authors: Alty Jane , Lawler Katherine , Salmon Katharine , McDonald Scott , Stuart Kimberley , Cleary Alison , Ma Jak , Rudd Kaylee , Wang Xinyi , Chiranakorn‐Costa Sigourney , Collins Jessica , Merl Helga , Lin Xiaoping , Vickers James C.
Published: August 2023

Objectives

Unequal access to cognitive assessments is a major barrier to timely diagnosis, especially for those living in rural or remote areas. ‘One‐stop’ cognitive clinic models are a proposed solution, but few such clinics exist. We evaluate the implementation of a new one‐stop State‐wide clinic model in Tasmania, Australia, where 27% of people live in rural/remote areas.

Methods

A novel single‐visit protocol has been developed, comprising interdisciplinary medical and cognitive assessments, research participation, consensus diagnosis and management plan. A cross‐sectional evaluation was undertaken using the RE‐AIM (reach, effectiveness, adoption, implementation, maintenance) framework and results benchmarked against the national Australian Dementia Network Registry.

Results

Over the first 52 consecutive weekly clinics: Reach: 130 adults were assessed (mean age [SD] 70.12 years [10.31]; 59.2% female) with 40 (36.8%) from rural/remote areas. Effectiveness: 98.5% (128/130) received a same‐day diagnosis: 30.1% (n = 40) Subjective Cognitive Decline, 35.4% (46) Mild Cognitive Impairment, 33.1% (43) dementia and one case inconclusive. Adoption: 22.9% (156) of General Practitioners referred patients. Implementation: Nearly all ‘ideal’ diagnostic clinical practices were met and >90% of surveyed patients reported ‘good/very good’ clinic experience. The wait from referral to diagnosis was 2 months shorter than other national Registry clinics (78 vs. 133 days).

Conclusions

This ‘one‐stop’ model provides an interdisciplinary consensus cognitive diagnosis quickly and is well accepted; this may reduce health inequities especially for people living in rural/remote areas. This cognitive clinic model may be of relevance to other centres worldwide and also provides a rich data source for research studies.
Single‐unit unrelated cord blood transplantation versus HLA‐matched sibling transplantation in adults with advanced myelodysplastic syndrome: A registry‐based study from the adult MDS working group of the Japanese society for transplantation and cellular therapy
Authors: Konuma Takaaki , Itonaga Hidehiro , Shimomura Yoshimitsu , Fujioka Machiko , Aoki Kazunari , Uchida Naoyuki , Onizuka Makoto , Jinguji Atsushi , Tanaka Masatsugu , Ueda Yasunori , Katayama Yuta , Sawa Masashi , Tanaka Haruyuki , Nakamae Hirohisa , Kawakita Toshiro , Maruyama Yumiko , Takahashi Satoshi , Ishimaru Fumihiko , Kanda Junya , Ichinohe Tatsuo , Atsuta Yoshiko
Published: August 2023

Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)‐1 and RAEB‐2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (n = 331) or single‐unit unrelated cord blood (UCB) (n = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90–1.34; P = 0.347), disease‐free survival (HR, 1.01; 95% CI, 0.84–1.23; P = 0.845), relapse (HR, 0.88; 95% CI, 0.68–1.15; P = 0.370), or non‐relapse mortality (HR, 1.15; 95% CI, 0.87–1.50; P = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24–0.33; P < 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23–0.36; P < 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft‐versus‐host disease (GVHD) (HR, 0.57; 95% CI, 0.44–0.75; P < 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32–0.67; P < 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.
Stakeholders' expectations of precision medicine: A qualitative study to identify areas of (mis)alignment
Authors: Knott Tanya , Creeden James , Horbach Benjamin , Rauch‐Zumbrägel Maximiliane , Vat Lidewij , Harnik Helena , Maravic Zorana
Published: August 2023

Background and Aims

To sustainably address challenges in implementing precision medicine (PM), coordinated efforts of different stakeholders are required. Understanding their expectations represents a first key step toward aligning on future actions and strategies. Here, we aimed to explore the expectations of different stakeholders from themselves and each other regarding PM.

Methods

This collaborative qualitative study was initiated by the global multistakeholder consortium From Testing to Targeted Treatments (FT3). Structured interviews were conducted with participants from five stakeholder groups: patients/patient advocates, healthcare providers (HCPs), researchers, policymakers/regulators/payers and industry representatives. A broad reach across geography, roles, experiences, and disease areas was sought. Results were analyzed by grounded theory methodology.

Results

All stakeholders stated that optimal implementation of PM can only be achieved through collaboration; industry representatives were the biggest promoters of collaboration. Stakeholders agreed that PM should be implemented focusing on the patient's best interest; HCPs were seen as important gatekeepers for PM by interacting directly with patients, and policymakers/payers were perceived as the most important drivers of access to PM. Areas of misalignment included the role of industry in clinical trial design and in access to PM (perceived as important by patients, HCPs and policymakers but not by industry representatives), and the stakeholders responsible for elaborating guidelines on PM use (patients indicated policymakers, while researchers indicated themselves). Priorities for optimal PM implementation and suggested actions included the need for enhancing high‐level policy focus, improving genomic literacy, optimizing the health technology assessment for PM, advocating for equitable access, promoting collaboration between industry and other stakeholder groups and development of reliable research standards.

Conclusion

Stakeholder expectations revealed in this study suggested that no stakeholder group can drive change on its own; a global, multistakeholder collaborative approach that brings together current programs and best practices to support universal access to PM is needed.
Prevalence of body dysmorphic disorder in rhinoplasty candidates: A systematic review and meta‐analysis
Authors: Nabavizadeh Sara S. , Naseri Reyhaneh , Sadeghi Erfan , Afshari Aylar , Dehdari Ebrahimi Niloofar , Sadeghi Alireza
Published: August 2023

Background

Body dysmorphic disorder (BDD) is a prevalent mental disorder, particularly in those seeking plastic surgery, leading to unnecessary surgeries and postsurgical dissatisfaction. Among the plastic surgeries, rhinoplasty is the most commonly sought, yet the data on prevalence of BDD among the candidates of rhinoplasty is limited. Therefore, this systematic review and meta‐analysis aimed to estimate the prevalence of BDD in rhinoplasty candidates.

Methods

The online libraries of Web of Science, PubMed, Cochrane Library, ProQuest, Research Square, Scopus, and Google Scholar were searched up to August 2022. Statistical analyses were performed using STATA software (v. 16). The heterogeneity was determined using the I2 statistic, and an overall estimated analysis was conducted. Subgroup analyses were performed on study year, age, gender, World Health Organization regional classification, sociodemographic index, country, sample size, and employed diagnostic tool. A meta‐regression analysis was performed to identify potential sources of heterogeneity.

Results

Out of 12,999 studies assessed, 18, with a combined sample size of 2132 individuals, met our criteria and were included in the study. The pooled prevalence of BDD was 32.7% (95% CI: 23.6−41.7; I2 = 96.45%). Subgroup analyses revealed the studies that were conducted in the European region (42.8%), with a sample size of ≥100 (40.2%), utilized the BDD modification of the Y‐BOCS (BDD‐YBOCS) diagnostic method (47.3%), and with a quality score of ≥6 (34.2%) demonstrated higher prevalence of BDD. The meta‐regression analysis identified a higher prevalence in the BDD‐YBOCS diagnostic method than in the BDD questionnaire (β: 0.23; 95% CI: 0.04−0.43; p = 0.022).

Conclusions

The prevalence of BDD is high in those seeking rhinoplasty. Clinicians should be aware of BDD symptoms to prevent unnecessary surgery and dissatisfaction. Public awareness through the media and access to affordable medical services should also be provided.
Examining the relationship between depression and medication adherence among elderlies suffering from cardiovascular disease referring to the clinics affiliated with Kermanshah University of Medical Sciences: A cross‐sectional study
Authors: Brimavandi Mina , Abbasi Parvin , Khaledi‐Paveh Behnam , Salari Nader
Published: August 2023

Background

In recent years, around 30% of all mortalities worldwide has been related to cardiovascular disease (CVD). The most important predictor solution of cardiovascular events is enhancing medication adherence. Meanwhile, the main reason behind development of physical disorders among the elderly is depression. In this regard, the present research was performed to determine the relationship between depression and medication adherence among the elderly suffering from CVD.

Methods

A cross‐sectional study was done via an analytical approach on 188 elderlies fulfilling the inclusion criteria. The participants were chosen through convenience nonrandomized sampling from March to July 2022. The data were collected through demographic and healthcare information form plus Madanloo chronic disease medication adherence and geriatric depression scale. The analysis of the data was done by SPSS 26 plus Stata 14.2.

Results

The mean depression score was 5.6(4.3) and the mean score of medication adherence in the elderlies was 168.03(23.85). The prevalence of depression was higher in women than in men (p = 0.015), and the elderlies differing from heart failure reported the minimum extent of medication adherence. The findings obtained from analysis of variance showed that age, level of education, and monthly level of income were among the effective demographic factors in the extent of depression and medication adherence (p < 0.05). Meanwhile, 26% of changes in medication adherence can be attributed to depression. Further, the results of the multiple linear regression model reported that depression, age, and polypharmacy are among the predictors of medication adherence.

Discussion and Conclusion

A weak to moderate relationship existed between depression and medication adherence among these elderlies. Given the growing elderly population, the importance of depression, and lack of medication adherence in incidence of CVD events, it is recommended to train the healthcare team to monitor the elderly regarding depression symptoms.
CCA repair or ECA ligation—Which middle cerebral artery occlusion is better in the reperfusion mouse model?
Authors: Hu Yue , Yang Zhen‐Hong , Yan Feng , Huang Shuang‐Feng , Wang Rong‐Liang , Han Zi‐Ping , Fan Jun‐Fen , Zheng Yang‐Min , Liu Ping , Luo Yu‐Min , Li Si‐Jie
Published: August 2023

A reliable animal model is essential for ischemic stroke research. The implications of the external carotid artery (ECA) transection or common carotid artery (CCA) ligation have been described. Thus, a modified animal model, the CCA‐repair model, has been established, and studies have shown that the CCA‐repair model has potential advantages over the CCA‐ligation model. However, whether the CCA‐repair model is superior to the ECA‐ligation model remains unclear. Sixty male C57BL/6 mice were randomly assigned to establish the CCA‐repair (n = 34) or ECA‐ligation (n = 26) models. Cerebral blood flow before middle cerebral artery occlusion (MCAO), immediately after MCAO and reperfusion were monitored and the operation duration, postoperative body weight, and food intake within 7 days, and the number of intraoperative and postoperative deaths within 7 days were recorded in the two models. Modified neurological severity scores and Bederson (0–5) scores were used to evaluate postoperative neurological function deficits on Days 1/3/5/7. 2,3,5‐Triphenyltetrazolium chloride staining was used to quantify lesion volume on Day 7 after the operation. We found the establishment of the CCA‐repair model required a longer total operation duration (p = 0.0175), especially the operation duration of reperfusion (p < 0.0001). However, there was no significant difference in body weight and food intake development, lesion volume and intragroup variability, neurological function deficits, mortality, and survival probability between the two groups. The CCA‐repair model has no significant advantage over the ECA‐ligation model. The ECA‐ligation model is still a better choice for focal cerebral ischemia.
Associations between placental pathology and poor intrauterine growth among a cohort of mother–infant singleton pairs in Leyte, the Philippines
Authors: Colt Susannah , Barry Christopher V. , Sagliba Marianne J. , Amoylen Amabelle J. , Tallo Veronica , Friedman Jennifer F. , Gundogan Fusun , McDonald Emily A.
Published: August 2023

Objective

Poor intrauterine growth has negative impacts for child growth and development and disproportionately affects children living in low‐resource settings. In the present study, we investigated relationships between placental pathologies and indicators of poor intrauterine growth.

Methods

We enrolled a longitudinal cohort of 279 mother–infant pairs from Leyte, the Philippines. Placental measures included characteristics, pathological findings, and immunohistochemistry. At birth, intrauterine growth was assessed using anthropometric measures, weight‐for‐gestational age, and the clinical assessment of nutritional status score (CANSCORE) for determining fetal malnutrition. Multivariate linear regression and log‐binomial regression models were applied, controlling for potential confounding factors.

Results

Maternal vascular malperfusion (MVM) was related to reduced birthweight (P < 0.0001), birth length (P = 0.002), head circumference (P = 0.001), and weight‐to‐length ratio (P = 0.016). MVM increased the risk for preterm delivery (P = 0.0005) and small for gestational age (SGA) (P = 0.016). Acute chorioamnionitis (P = 0.013) and MVM (P = 0.021) both led to an increased risk for fetal malnutrition defined by CANSORE<25. Villous tissue activated caspase‐3 was associated with lower birth length (P = 0.0006), higher weight‐to‐length ratio (P = 0.004), reduced risks for SGA (P = 0.011) and low weight‐to‐length ratio for gestational age (P = 0.004).

Conclusion

The present study applied comprehensive measures for intrauterine growth and demonstrates that low placental weight and placental pathology, chiefly MVM, contribute to poor intrauterine growth. A better understanding of the mechanistic role of specific placental pathologies on adverse newborn outcomes will provide opportunities for reducing incidence of poor intrauterine growth and associated long‐term morbidities.
Performance analysis ofstate‐of‐the‐art CNNarchitectures for brain tumour detection
Authors: Khushi Hafiz Muhammad Tayyab , Masood Tehreem , Jaffar Arfan , Akram Sheeraz , Bhatti Sohail Masood
Published: August 2023

Deep learning models, such as convolutional neural network (CNN), are popular now a day to solve various complex problems in medical and other fields, such as image classification, object detection, recommendation of images, processing of natural languages and video and image analysis. So, the idea of studying the architecture of CNNs has gotten a lot of attention and become popular. This study analysed and contrasted the performance of many different CNN models trained on the publicly accessible Br35h dataset for the detection of brain tumours. These models included the LeNet, AlexNet, VGG16, VGG19 and ResNet50. Several optimisers were used in this research to fine‐tune the performance of the CNN model. These included Adam (adaptive moment estimation), SGD (stochastic gradient descent) and RMSprop (root‐mean‐square propagation). Accuracy, miss‐classification rate, sensitivity, specificity, NPV (negative predictive value), PPV (positive predictive value), F1‐score and false omission rate (FOR) were used to assess the efficacy of five different CNN architectures trained using three different optimisers. The experimental results showed that AlexNet architecture with SGD optimiser performed better than other CNN architecture with different optimisers and achieved the highest accuracy of 98.79% with a miss classification rate of 1.20%. It also achieved 98.98% sensitivity, 98.58% specificity, 98.93% NPV, 98.65% PPV, 98.82% F1‐score and 1.06% FOR.
MacD‐Net: An automatic guided‐ensemble approach for macular pathology detection using optical coherence tomography images
Authors: Maurya Ritesh , Pandey Nageshwar Nath , Joshi Rakesh Chandra , Dutta Malay Kishore
Published: August 2023

In this work, a novel guided‐ensemble approach has been proposed for an automated diagnosis of three different types of retinal disorders, such as drusen, choroidal neovascularization (CNV) and diabetic macular edema (DME). These conditions, if left untreated, can lead to vision loss. In the proposed approach, four different pre‐trained CNNs such as MobileNetV1, EfficientNetB3, NASNetMobile and XceptionNet have been fine‐tuned for that purpose and the prediction score obtained by each CNN in an ensemble has been combined based on their validation accuracies. The proposed guided‐ensemble approach has been trained and tested on the public dataset consisting of 84 495 retinal OCT images for training and 1000 unseen images for testing. These images were graded by the experts into four categories, such as CNV, DME, drusen and normal. The proposed approach has outperformed the other methods by obtaining an accuracy of 99.8% in classifying four different classes of retinal OCT images.
Data governance for wicked problems: A case from the Thai health system
Authors: Gunawong Panom
Published: August 2023

This study examined how data governance practices in multi‐agency organizations manifest while trying to solve a wicked problem. This study adopted the data governance framework to analyze the Working Group that is responsible for opium addiction and treatment projects in Thailand. This framework comprises five decision domains of data: data principles, data quality, metadata, data access, and data lifecycle. The results showed that the Working Group did not have strong data principles among the relevant agencies and faced local obstacles. This led to uncertainty in the other four areas. It demonstrated, however, some effective outcomes by improvising its specific approach, which considers the relationships between various stakeholders in their dynamic adaptations within the overall data governance process. The Working Group practiced localized framework strategies, which consisted of eight approaches: data consensus in the knowledge network, strong structure, information integrity and cultural awareness, flexibility of organizational integration, dynamic adjustment process, effective information sharing, unlocking stagnations, and data governance cycles. All these strategic approaches compensated for the low performance of the current universal data governance framework.
In vitro assessment of inflammatory skin potential of poly(methyl methacrylate) at non‐cytotoxic concentrations
Authors: Barraza‐Vergara Luisa F. , Carmona‐Sarabia Lesly , Torres‐García Wandaliz , Domenech‐García Maribella , Mendez‐Vega Janet , Torres‐Lugo Madeline
Published: August 2023

Poly(methyl methacrylate) (PMMA) is considered an attractive substrate material for fabricating wearable skin sensors such as fitness bands and microfluidic devices. Despite its widespread use, inflammatory and allergic responses have been attributed to the use of this material. Therefore, the main objective of this study was to obtain a comprehensive understanding of potential biological effects triggered by PMMA at non‐cytotoxic concentrations using in vitro models of NIH3T3 fibroblasts and reconstructed human epidermis (RhE). It was hypothesized that concentrations that do not reduce cell viability are sufficient to activate pathways of inflammatory processes in the skin. The study included cytotoxicity, cell metabolism, cytokine quantification, histopathological, and gene expression analyses. The NIH3T3 cell line was used as a testbed for screening cell toxicity levels associated with the concentration of PMMA with different molecular weights (MWs) (i.e., MW ~5,000 and ~15,000 g/mol). The lower MW of PMMA had a half‐maximal inhibitory concentration (IC50) value of 5.7 mg/cm2, indicating greater detrimental effects than the higher MW (IC50 = 14.0 mg/cm2). Non‐cytotoxic concentrations of 3.0 mg/cm2 for MW ~15,000 g/mol and 0.9 mg/cm2 for MW ~5,000 g/mol) induced negative metabolic changes in NIH3T3 cells. Cell viability was severely reduced to 7% after the exposure to degradation by‐products generated after thermal and photodegradation degradation of PMMA. PMMA at non‐cytotoxic concentrations still induced overexpression of pro‐inflammatory cytokines, chemokines, and growth factors (IL1B, CXCL10, CCL5, IL1R1, IL7, IL17A, VEGFA, FGF2, IFNG, IL15) on the RhE model. The inflammatory response was also supported by histopathological and gene expression analyses of PMMA‐treated RhE, indicating tissue damage and gene overexpression. Results suggested that non‐cytotoxic concentrations of PMMA (3.0 to 5.6 mg/cm2 for MW ~15,000 g/mol and 0.9 to 2.1 mg/cm2 for MW ~5,000 g/mol) were sufficient to negatively alter NIH3T3 cells metabolism and activate inflammatory events in the RhE skin.
The phenotype of adults with complicated eosinophilic esophagitis is dominated by a 5‐year longer diagnostic delay: A population‐based study of the DanEoE cohort
Authors: Henriksen Stine D , Hansen Stine K , Heinesen Mia , Terkelsen Jacob H , Hollænder Martin , Bredal Kasper , Melgaard Dorte , Krarup Anne L
Published: August 2023

Background and Aim

The DanEoE is a previously described population‐ and register‐based cohort of 236 adult patients with eosinophilic esophagitis (EoE) in a well‐defined Danish region with a population of 580 000 and free medical treatment. The aim of the study was to compare the phenotype and treatment response between EoE patients with complications to patients without complications at diagnosis.

Methods

A retrospective cross‐sectional study of the DanEoE cohort's 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. Patients were divided into a group who had had complications (dilated or food bolus obstruction [FBO]) before or at the diagnosis, and a group without.

Results

At the diagnostic endoscopy, 61% had never had a complication, and 39% had either had FBO (n = 77) or been dilated (n = 15). The complicated group had the same mean age at symptom debut (37 [SD = 16] vs 37 [SD = 17] years, P = 1.0), but were diagnosed significantly later with a resulting longer diagnostic delay (13 [SD = 13] vs 7.9 [SD = 11] years, P = 0.01). Almost half of all patients were never treated to symptomatic remission (uncomplicated 40%, complicated 49%). The histological remission was not secured in the majority (uncomplicated 68%, complicated 70%). Despite this, <15% of patients with previous FBO experienced this after the diagnosis.

Conclusion

In the population‐based DanEoE cohort, results indicated that the complicated EoE phenotype was a patient with a 5‐year longer diagnostic delay. In the current study, the complication status did not predict the treatment response.
Screening data from 19 patients with late‐onset Pompe disease for a phase I clinical trial of AAV8 vector‐mediated gene therapy
Authors: Hannah William B. , Case Laura E. , Smith Edward C. , Walters Crista , Bali Deeksha , Kishnani Priya S. , Koeberl Dwight D.
Published: August 2023

Late‐onset Pompe disease (LOPD) is a multisystem disorder with significant myopathy. The standard treatment is enzyme replacement therapy (ERT), a therapy that is lifesaving, yet with limitations. Clinical trials have emerged for other potential treatment options, including adeno‐associated virus (AAV) gene therapy. We present clinical parameters and AAV antibody titers for 19 individuals with LOPD undergoing screening for a Phase I clinical trial with an AAV serotype 8 vector targeting hepatic transduction (AAV2/8‐LSPhGAA). Reported clinical parameters included GAA genotype, assessments of muscle function, upright and supine spirometry, anti‐recombinant human GAA antibody titers, and biomarkers. Variability in measured parameters and phenotypes of screened individuals was evident. Eligibility criteria required that all participants have six‐minute walk test (6MWT) and upright forced vital capacity (FVC) below the expected range for normal individuals, and were stably treated with ERT for >2 years. All participants had Pompe disease diagnosed by enzyme deficiency, and all had the common c.‐32‐13T>G LOPD pathogenic variant. Screening identified 14 patients (74%) with no or minimal detectable neutralizing antibodies against AAV8 (titer ≤1:5). 6MWT distance varied significantly (percent of expected distance ranging from 24% to 91% with an average of 60 and standard deviation of 21). Upright FVC percent predicted ranged from 35% predicted to 91% predicted with an average of 66 and standard deviation of 18. None of the participants had significantly elevated alanine transaminase, which has been associated with LOPD and could complicate screening for hepatitis related to AAV gene therapy. We review the parameters considered in screening for eligibility for a clinical trial of AAV8 vector‐mediated gene therapy.
Feasibility of Multiparametric Perfusion Assessment in Diabetic Foot Ulcer Using Intravoxel Incoherent Motion and Blood Oxygenation‐Level Dependent MRI
Authors: Edwards Scott J. , Yao Jingting , Schechter Marcos C. , Fayfman Maya , Santamarina Gabriel , Feiweier Thorsten , Blanco Gerardo , Alvarez Jessica , Risk Benjamin B. , Rajani Ravi , Reiter David A.
Published: August 2023

Background

Patients with type‐2 diabetes (T2DM) are at increased risk of developing diabetic foot ulcers (DFU) and experiencing impaired wound healing related to underlying microvascular disease.

Purpose

To evaluate the sensitivity of intra‐voxel incoherent motion (IVIM) and blood oxygen level dependent (BOLD) MRI to microvascular changes in patients with DFUs.

Study Type

Case–control.

Population

20 volunteers who were age and body mass index matched, including T2DM patients with DFUs (N = 10, mean age = 57.5 years), T2DM patients with controlled glycemia and without DFUs (DC, N = 5, mean age = 57.4 years) and healthy controls (HC, N = 5, mean age = 52.8 years).

Field strength/Sequence

3T/multi‐b‐value IVIM and dynamic BOLD.

Assessment

Resting IVIM parameters were obtained using a multi‐b‐value diffusion‐weighted imaging sequence and two IVIM models were fit to obtain diffusion coefficient (D), pseudo‐diffusion coefficient (D*), perfusion fraction (f) and microvascular volume fraction (MVF) parameters. Microvascular reactivity was evaluated by inducing an ischemic state in the foot with a blood pressure cuff during dynamic BOLD imaging. Perfusion indices were assessed in two regions of the foot: the medial plantar (MP) and lateral plantar (LP) regions.

Statistical Tests

Effect sizes of group mean differences were assessed using Hedge's g adjusted for small sample sizes.

Results

DFU participants exhibited elevated D*, f, and MVF values in both regions (g ≥ 1.10) and increased D (g = 1.07) in the MP region compared to DC participants. DC participants showed reduced f and MVF compared to HC participants in the MP region (g ≥ 1.06). Finally, the DFU group showed reduced tolerance for ischemia in the LP region (g = −1.51) and blunted reperfusion response in both regions (g < −2.32) compared to the DC group during the cuff‐occlusion challenge.

Data Conclusion

The combined use of IVIM and BOLD MRI shows promise in differentiating perfusion abnormalities in the feet of diabetic patients and suggests hyperperfusion in DFU patients.

Level of Evidence

1

Technical Efficacy

Stage 1
Probing Evidence of Cerebral White Matter Microstructural Disruptions in Ischemic Heart Disease Before and Following Cardiac Rehabilitation: A Diffusion Tensor MR Imaging Study
Authors: Poirier Stefan E. , Suskin Neville G. , Khaw Alexander V. , Thiessen Jonathan D. , Shoemaker Joel K. , Anazodo Udunna C.
Published: August 2023

Background

Ischemic heart disease (IHD) is linked to brain white matter (WM) breakdown but how age or disease effects WM integrity, and whether it is reversible using cardiac rehabilitation (CR), remains unclear.

Purpose

To assess the effects of brain aging, cardiovascular disease, and CR on WM microstructure in brains of IHD patients following a cardiac event.

Study Type

Retrospective.

Population

Thirty‐five IHD patients (9 females; mean age = 59 ± 8 years), 21 age‐matched healthy controls (10 females; mean age = 59 ± 8 years), and 25 younger controls (14 females; mean age = 26 ± 4 years).

Field Strength/Sequence

3 T diffusion‐weighted imaging with single‐shot echo planar imaging acquired at 3 months and 9 months post‐cardiac event.

Assessment

Tract‐based spatial statistics (TBSS) and tractometry were used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in cerebral WM between: 1) older and younger controls to distinguish age‐related from disease‐related WM changes; 2) IHD patients at baseline (pre‐CR) and age‐matched controls to investigate if cardiovascular disease exacerbates age‐related WM changes; and 3) IHD patients pre‐CR and post‐CR to investigate the neuroplastic effect of CR on WM microstructure.

Statistical Tests

Two‐sample unpaired t‐test (age: older vs. younger controls; IHD: IHD pre‐CR vs. age‐matched controls). One‐sample paired t‐test (CR: IHD pre‐ vs. post‐CR). Statistical threshold: P < 0.05 (FWE‐corrected).

Results

TBSS and tractometry revealed widespread WM changes in older controls compared to younger controls while WM clusters of decreased FA in the fornix and increased MD in body of corpus callosum were observed in IHD patients pre‐CR compared to age‐matched controls. Robust WM improvements (increased FA, increased AD) were observed in IHD patients post‐CR.

Data Conclusion

In IHD, both brain aging and cardiovascular disease may contribute to WM disruptions. IHD‐related WM disruptions may be favorably modified by CR.

Level of Evidence

3

Technical Efficacy

Stage 2
Bacterial assemblages structure in intensive cultivations of the microalga Tetradesmus obliquus
Authors: Bucheli Jaimet , Cella Herculano , Nader Camila , Oliveira Carlos Yure B. , Bastolla Camila Lisarb V. , Lopes Rafael Garcia , Pereira Gabriella do Vale , Karam João , Derner Roberto Bianchini
Published: August 2023

The present study shows the characterization of the bacterial communities associated with different systems during the cultivation of the microalga Tetradesmus obliquus. For that, sequential cultivation was performed in three different systems: (1) Photobioreactor bench‐scale; (2) flat‐panel photobioreactor; and (3) thin‐layer cascade. Cultures were monitored daily for growth parameters and biomass samples were collected for characterization of bacterial communities using metagenomic. A total of 195,177 reads were produced, resulting in the identification of 72 OTUs. In the grouping of bacterial communities, 3 phyla, 6 classes, 28 families, and 35 taxa were found. The bacteria Brevundimonas and Porphyrobacter had a higher relative abundance compared with other taxa found. These taxa were present in all cultivation systems forming a possible core community. Bacterial communities associated with different cultivation systems of the microalga T. obliquus showed an increase in taxa richness and diversity in the super‐intensive and intensive systems.
CMIP6‐projected changes in drought over Xinjiang, Northwest China
Authors: Zhang Xiaolu , Wang Xiaoxin , Zhou Botao
Published: August 2023

Xinjiang, located in Northwest China, is a typical arid and semiarid region. In this region, frequent droughts have caused great losses in agricultural production and social economy. Therefore, changes in drought over Xinjiang have attracted considerable attention. This study projects the drought changes over Xinjiang during the 21st century, based on the Coupled Model Intercomparison Project Phase 6 (CMIP6) simulations under three Shared Socioeconomic Pathways (SSPs). The Standardized Precipitation Evapotranspiration Index (SPEI) is applied to measure drought variation. After quantitatively evaluating the performance of 25 CMIP6 models in annual and seasonal precipitation and evapotranspiration in Xinjiang during 1995–2014, we select 13 preferred models for projection. The projection results show significant decreasing trends in annual SPEI during 2021–2100 in Xinjiang, with the trends of −0.1/10a, −0.1/10a and −0.2/10a under SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5, respectively. For seasons, the projected decreasing trends of SPEI in summer, autumn and spring are greater than that in winter. Relative to 1995–2014, during 2081–2100, moderate and severe droughts are projected to occupy a major increase in drought areas in Xinjiang under the three scenarios. In addition, drought tends to become more frequent and intense and last longer especially under higher scenarios. Under SSP5‐8.5, the projected regionally averaged drought frequency, intensity and duration increase by 15%, 8% and 1 month at the end of the 21st century. On the whole, the intermodel uncertainties of the projected changes in drought over Xinjiang increase with time in each emission. The findings of this study can provide information for decision makers to develop drought adaptation measures.
Improvisation Exercises Increase Negotiators' Divergent Thinking, and Sometimes their Negotiation Outcomes
Authors: Harinck Fieke , Dooren Loes
Published: August 2023

Two studies investigated the effect of a short improvisation intervention (theatrical improvisation in Study 1, musical improvisation in Study 2) on negotiation processes and outcomes. The expectation was that an improvisation exercise, compared to a control condition in which participants engaged in jigsaw puzzling, would result in better negotiation agreements via higher levels of divergent thinking. Results showed that improvisation exercise increased participants' divergent thinking, compared to the control condition. The effects on negotiation processes and outcomes, however, only partly supported the predictions. In Study 2, improvisation exercise had an indirect influence on negotiation outcomes via divergent thinking, and in Study 1 improvisation exercise did influence divergent thinking but did not influence negotiation outcomes. So improvisation exercise increases divergent thinking, and sometimes this heightened divergent thinking results in higher negotiation outcomes.
Treating the invisible: Subclinical actinic keratosis detected by imiquimod
Authors: Kopera Daisy , Torrano Joachim , Soyer H. Peter
Published: August 2023

Background

Skin in UV‐exposed areas may develop UV‐induced actinic damage in DNA sequences leading to proliferation of keratinocyte carcinoma, a type of non‐melanoma skin cancer. Actinic keratosis (AK) represents early‐stage in situ squamous cell carcinoma. It develops from the basal cell layer and may be present in subclinical stages, being reported as field cancerization, even before being clinically visible. Thus, we hypothesise that from the age of 50 + UV‐exposed skin features subclinical forms of AKs without visible skin lesions.

Objectives

This study aims at clarifying the existence of the clinically invisible, early stages of AKs on chronically UV‐exposed skin without showing clinically evident features of AK.

Methods

46 volunteers (26 females and 20 males) aged 50+ with signs of moderate to severe UV‐damage (photodamage) applied imiquimod 3.75% creme on their entire face every night for a 2‐week period. All participants kept a diary noting onset, severity of inflammatory reactions, and unexpected side effects.

Results

More than 90% of participants without clinical evidence of AK showed inflammatory reactions on topical treatment with imiquimod on their face demonstrating an interaction between UV‐damaged mutated keratinocytes and the topically applied immunomodifier, thus proofing the presence of subclinical AKs.

Conclusions

The action of imiquimod is not restricted to visible AK lesions, but often includes their vicinity, suggesting that neoplastic processes are frequent at a cellular level, not confined to clinically evident lesions, supporting the concept of field cancerization. Thus, subclinical AKs do exist in an early, macroscopically invisible state and may be targeted by imiquimod or 5‐FU. At this stage, AKs are being treated before diagnosis by usual clinical means, and well before potential progression to invasive squamous cell carcinoma (SCC). Eventually, imiquimod 3.75% cream could be recommended in UV‐exposed skin to prevent the presumptive development of AK and later on, early SCC.
Environmental Risk Factors for Pediatric Epistaxis vary by Climate Zone
Authors: Wei Eric X. , Green Allen , Chang Michael T. , Hwang Peter H. , Sidell Douglas R. , Qian Z. Jason
Published: August 2023

Introduction and Objective

Prior studies have provided variable results regarding environmental risk factors for epistaxis. These studies were conducted in varying climate zones, which may explain discrepancies in results. The objective of this study is to investigate correlations between season, temperature, and humidity on frequency of pediatric epistaxis across climate zones.

Methods

Children seen in the outpatient setting for epistaxis were identified from the 2007–2010 IBM MarketScan database. Climate zones were assigned according to International Energy Conservation Code (IECC) classification, where temperature zones in the United States and territories were assigned on an ordinal scale from 1 (tropical) to 8 (subarctic), and humidity zones were categorized as moist, dry, or marine. The control population was a sample of all well‐child visits matched by age and county.

Results

We identified 184,846 unique children seen for epistaxis and 1,897,012 matched controls. Moderate temperature zones were associated with lower odds of epistaxis compared with the hottest and coldest zones. Humidity was associated inversely with epistaxis rates in moderate temperature zones but was not a significant predictor of epistaxis in climates with extreme heat. Additionally, summer was associated with lower odds of epistaxis compared to winter. Interestingly, however, there were significantly higher rates of cautery procedures during summer months, driven largely by increased procedures performed in clinic, as opposed to the operating room or emergency room.

Conclusions

Environmental risk factors for epistaxis vary by climate zone. The model presented reconciles prior reports and may allow for more personalized clinical management based on regional climate.

Level of Evidence

3 Laryngoscope, 134:1450–1456, 2024
Mucosa‐associated Lymphoid Tissue Misdiagnosis as Glomus Tympanicum
Authors: Cho Yongmin , Kim Angela Y. , Song Jae‐Jun , Chae Sung‐Won
Published: August 2023

Middle ear tumors are diverse, but relatively uncommon. The most frequent tumor in the middle ear is glomus tumor, followed by others such as schwannoma and cholesteatoma. We experienced a case of Mucosa‐associated lymphoid tissue hyperplasia as a middle ear tumor. The mass behind tympanic membrane appeared a hypervascular tumor, mimicking a glomus tumor, but the form of multiple separate masses in middle ear and mastoid cavity was the distinguishing feature that set it apart from a glomus tumor. Additionally, another characteristic was its tendency to easily shrink under pressure. This characteristic should be considered when encounter a hypervascular looking middle ear mass. Laryngoscope, 134:1894–1896, 2024
Cattle–compost–soil: The transfer of antibiotic resistance in livestock agriculture
Authors: Abbas Fadhel , Thomas Phil , Cully‐Duse Bianca , Andronicos Nicholas M. , Winter Gal
Published: August 2023

Antibiotic resistance is a major global health threat. Agricultural use of antibiotics is considered to be a main contributor to the issue, influencing both animals and humans as defined by the One Health approach. The purpose of the present study was to determine the abundance of antibiotic‐resistant bacterial populations and the overall bacterial diversity of cattle farm soils that have been treated with animal manure compost. Soil and manure samples were collected from different sites at Tullimba farm, NSW. Cultures were grown from these samples in the presence of 11 commonly used antibiotics and antibiotic‐resistant bacteria (ARB) colonies were identified. Soil and manure bacterial diversity was also determined using 16S ribosomal RNA next‐generation sequencing. Results showed that ARB abundance was greatest in fresh manure and significantly lower in composted manure. However, the application of composted manure on paddock soil led to a significant increase in soil ARB abundance. Of the antibiotics tested, the number of ARB in each sample was greatest for antibiotics that inhibited the bacterial cell wall and protein synthesis. Collectively, these results suggest that the transfer of antibiotic resistance from composted animal manure to soil may not be solely mediated through the application of live bacteria and highlight the need for further research into the mechanism of antibiotic resistance transfer.
27‐Hydroxycholesterol Drives the Spread of α‐Synuclein Pathology in Parkinson's Disease
Authors: Dai Lijun , Wang Jiannan , Zhang Xingyu , Yan Mingmin , Zhou Lingyan , Zhang Guoxin , Meng Lanxia , Chen Liam , Cao Xuebing , Zhang Zhaohui , Wang Gaohua , Zhang Zhentao
Published: August 2023

Background

The accumulation and aggregation of α‐synuclein (α‐Syn) are characteristic of Parkinson's disease (PD). Epidemiological evidence indicates that hyperlipidemia is associated with an increased risk of PD. The levels of 27‐hydroxycholesterol (27‐OHC), a cholesterol oxidation derivative, are increased in the brain and cerebrospinal fluid of patients with PD. However, whether 27‐OHC plays a role in α‐Syn aggregation and propagation remains elusive.

Objective

The aim of this study was to determine whether 27‐OHC regulates α‐Syn aggregation and propagation.

Methods

Purified recombinant α‐Syn, neuronal cultures, and α‐Syn fibril‐injected mouse model of PD were treated with 27‐OHC. In addition, CYP27A1 knockout mice were used to investigate the effect of lowering 27‐OHC on α‐Syn pathology in vivo.

Results

27‐OHC accelerates the aggregation of α‐Syn and enhances the seeding activity of α‐Syn fibrils. Furthermore, the 27‐OHC‐modified α‐Syn fibrils localize to the mitochondria and induce mitochondrial dysfunction and neurotoxicity. Injection of 27‐OHC‐modified α‐Syn fibrils induces enhanced spread of α‐Syn pathology and dopaminergic neurodegeneration compared with pure α‐Syn fibrils. Similarly, subcutaneous administration of 27‐OHC facilitates the seeding of α‐Syn pathology. Genetic deletion of cytochrome P450 27A1 (CYP27A1), the enzyme that converts cholesterol to 27‐OHC, ameliorates the spread of pathologic α‐Syn, degeneration of the nigrostriatal dopaminergic pathway, and motor impairments. These results indicate that the cholesterol metabolite 27‐OHC plays an important role in the pathogenesis of PD.

Conclusions

27‐OHC promotes the aggregation and spread of α‐Syn. Strategies aimed at inhibiting the CYP27A1‐27‐OHC axis may hold promise as a disease‐modifying therapy to halt the progression of α‐Syn pathology in PD. © 2023 International Parkinson and Movement Disorder Society.
Expanding the allelic spectrum of ELOVL4‐related autosomal recessive neuro‐ichthyosis
Authors: Alabdulrazzaq Fatima , Alanzi Talal , Al‐Balool Haya H. , Gardham Alice , Wakeling Emma , Leitch Harry G. , AlSayed Moeenaldeen , Abdulrahim Maha , Aladwani Abdulaziz , Romito Antonio , Kampe Kapil , Ferdinandusse Sacha , Aboelanine Ashraf H. , Abdullah Amira , Alwadani Amal , Bastaki Laila , Vaz Frédéric M. , Bertoli‐Avella Aida M. , Marafi Dana
Published: August 2023

Background

Very long‐chain fatty acids (VLCFAs) composed of more than 20 carbon atoms are essential in the biosynthesis of cell membranes in the brain, skin, and retina. VLCFAs are elongated beyond 28 carbon atoms by ELOVL4 enzyme. Variants in ELOVL4 are associated with three Mendelian disorders: autosomal dominant (AD) Stargardt‐like macular dystrophy type 3, AD spinocerebellar ataxia, and autosomal recessive disorder congenital ichthyosis, spastic quadriplegia and impaired intellectual development (ISQMR). Only seven subjects from five unrelated families with ISQMR have been described, all of which have biallelic single‐nucleotide variants.

Methods

We performed clinical exome sequencing on probands from four unrelated families with neuro‐ichthyosis.

Results

We identified three novel homozygous ELOVL4 variants. Two of the families originated from the same Saudi tribe and had the exact homozygous exonic deletion in ELOVL4, while the third and fourth probands had two different novel homozygous missense variants. Seven out of the eight affected subjects had profound developmental delay, epilepsy, axial hypotonia, peripheral hypertonia, and ichthyosis. Delayed myelination and corpus callosum hypoplasia were seen in two of five subjects with brain magnetic rosonance imaging and cerebral atrophy in three.

Conclusion

Our study expands the allelic spectrum of ELOVL4‐related ISQMR. The detection of the same exonic deletion in two unrelated Saudi family from same tribe suggests a tribal founder mutation.