As new pharmacological and surgical treatments developed, neuroimaging became one of the most promising biomarkers for diagnosis of Parkinson's Disease (PD) and Parkinsonism and monitoring disease progression and treatment. This Research Topic collected 25 articles  that applied neuroimaging in PD and Parkinsonism. Imaging types included diffusion-MRI, proton-MRI, susceptibility-weighted imaging (SWI), structural and functional MRI (fMRI), glucose- and tau- positron emission tomography (PET), single photon emission computed tomography (SPECT), dopamine buffering capacity imaging, and as well as combinations of these approaches. We classified these articles into the following categories.These review articles have indicated that neuroimaging techniques are useful markers in detecting early changes in PD and parkinsonian syndromes. The brainstem and substantia nigra (SN) have been identified as vulnerable structures in PD and Parkinsonism, and neuromelanin-sensitive imaging has been shown to detect dorsolateral nigral hyperintensity, which implies SN neurodegeneration in Parkinsonism. Additionally, cognitive dysfunction is a significant non-motor feature of PD, and functional and anatomical imaging characteristics have been identified as potential predictors of cognitive impairment in PD. However, further research is required to fully understand the underlying mechanisms of cognitive impairment in PD and to develop more effective diagnostic and treatment options.Pyatigorskaya et al. found a notable size effect in the SN in PD for R2* increase (effect size = 0.84), for SWI measurements (effect size = 1.14), and for quantitative susceptibility mapping (QSM) increase (effect size = 1.13). Correlations between imaging measurements and motor severity were mostly observed for QSM. These studies yielded consistently increased iron content in PD using R2, SWI, or QSM techniques, suggesting that these MRI measurements provide reliable markers of iron deposition in PD. Further, QSM appeared more robust and reproducible than R2* and more suitable to multicenter samples.In a meta-analysis of 46 SN iron imaging studies in PD, Bergamino et al. reviewed diffusion MRI studies in early-stage PD, with a focus on recent advances in the diffusion tensor imaging (DTI) methodology, such as the advantages and disadvantages of different diffusion MRI techniques, analysis methods, and software employed. These advanced methods have been shown to detect diffuse white matter changes in early-stage PD.Arribarat et al. proposed that the brainstem is the earliest vulnerable structure in multiple system atrophy (MSA) or PD. In a brief overview on recent advances in brainstem-related MRI markers in PD and Parkinsonism, the authors summarized the ability of brainstem imaging, including iron-sensitive MRI, nigrosome imaging, neuromelanin-sensitive MRI, DTI, and advanced diffusion imaging, to discriminate patients with PD from controls or to discriminate patients with PD from patients with atypical parkinsonism. A standardized multimodal brainstem-dedicated MRI approach is promising for detecting early changes in PD and parkinsonian syndromes.Saeed et al. reviewed studies that use neuroimaging biomarkers, including structural MRI, diffusion MRI, functional MRI, proton magnetic resonance spectroscopy, and transcranial B-mode sonography, for measuring SN and lentiform nucleus echogenicity, as well as SPECT and PET that are used to improve diagnostic certainty and ensure more informed diagnostic decisions.Based on predominant protein aggregates observed within the brain, Parkinsonian disorders are categorized as a-synucleinopathies and tauopathies. Chougar et al. reported the development of several imaging signs/measurements, some of which have shown individual-level diagnostic utility. Specifically, neuromelanin-sensitive imaging detecting dorsolateral nigral hyperintensity implies SNc neurodegeneration in Parkinsonism; neuromelanin signal loss in coeruleus is associated with rapid eye movement sleep behavior disorder (RBD), and is an early sign of PD and MSA. The midbrain to pons ratio and the MR Parkinsonism Index (MRPI) are robust clinical biomarkers of progressive supranuclear palsy (PSP), while abnormalities in the putamen, pons, and cerebellum strongly support the diagnosis of MSA.By reviewing multimodal MRI in Parkinsonian syndromes, Sasikumar and Strafella identified functional and anatomical imaging characteristics that predict cognitive impairment in PD, the limitations that challenge this process, and the avenues of potential research.Cognitive dysfunction is a significant non-motor feature of PD; however, the pathophysiology of cognitive impairment in PD cannot be explained by dopaminergic loss alone. A review article by Neuroimaging techniques, such as DTI, diffusion kurtosis imaging (DKI), and functional near infrared spectroscopy (fNIRS), have been found to be useful in the early diagnosis and tracking of PD. The use of DTI and DKI in particular has shown promise in identifying changes in the brain's microstructure, which may aid in diagnosing early-stage PD. Additionally, the use of fNIRS has been found to be useful in assessing changes in cortical activity during tasks such as walking, which may be indicative of compensation for executive deficits in patients with PD. Furthermore, the new assessment of dopamine transporter (DAT) using [18F]LBT-999 and short PET acquisition can be an alternative to assess dopaminergic presynaptic injury in PD using a single 10 min acquisition. These findings suggest that neuroimaging may be an important tool in the early diagnosis of PD.Zhang and Burock reviewed DTI analyses of PD, focusing on the utility of DTI as a marker of diagnosing early PD, correlating motor symptoms, tracking disease progression, and treatment effects. This review article highlighted a complex pattern of fractional anisotropic (FA) changes in the first few years of PD, in which, FA shows compensatory responses to motor deficits in some motor areas, and these increased anisotropic findings can be observed in young-onset and early-stage PD.Guan J. et al. evaluated mean kurtosis (MK) values in the bilateral red nucleus and SN using DKI in 26 (14 early-stage and 12 advanced-stage) patients with PD and 15 healthy controls. The authors found that MK values in the bilateral SN were significantly lower in all patients than in controls. Advanced-stage PD had a lower MK in the left SN than that of early-stage PD. While no significant differences in FA or mean diffusivity (MD) were detected between groups, the findings suggested that DKI measurements of the SN may aid the diagnoses of early PD and PD stages.Bbingbing et al. also examined DKI and DTI in the basal ganglia nuclei and found that MD in the globus pallidus provides the largest area under the Receiver Operating Characteristic curve for distinguishing PD from healthy controls. Furthermore, all DKI parameters correlated to the Mini-Mental State Examination, and these can be a useful indicator of microstructures in extrapyramidal nuclei in PD.Ranchet et al. measured cortical activity in the dorsolateral prefrontal cortex (DLPFC) by analyzing oxy-hemoglobin (1HbO2) and deoxy-hemoglobin (1HbR) using a functional near infrared spectroscopy (fNIRS) device, to asses DLPFC activation during usual walking and dual-task walking conditions in patients with PD. The authors suggested that the increased DLPFC activity in patients during usual walking suggests a potential compensation for executive deficits.Similar to the imaging of functional activity using task-based fMRI, Ribeiro et al. proposed a novel assessment of DAT using [18F]LBT-999 and a short PET acquisition. The authors reported that the striatal uptake of DAT was lower than in controls, which was confirmed by binding potential, distribution volume ratios, and ratios calculated for both the striatal nuclei and SN, which were significantly lower in patients with PD compared with controls. The study demonstrated that [18F]LBT-999 PET could be an alternative to assess dopaminergic presynaptic injury in PD using a single 10 min acquisition.Neuroimaging has played a vital role in understanding the progression and treatment-induced syndromes of PD. Studies have shown that MRI-based gray matter density can detect an organized pattern of atrophy across disease progression and that a novel pharmacological fMRI (phMRI) method can objectively quantify disease severity in PD. Additionally, pulvinar thalamic hypointensity and the putamen-to-thalamus Hyper-Perfusion/Hypo-Metabolism Index (PHI) have been proposed as potential biomarkers for cognitive worsening and Levodopa-induced dyskinesia (LID), respectively.Blair et al. retrospectively used MRI-based gray matter density in regions of interest (ROIs) in PD studies of 228 patients with early PD, 136 patients with advanced PD, and 103 control subjects to assess the caudal-rostral pattern of the progression of Lewy body pathology in PD. The study found that patients with advanced PD had a lower gray matter density in the basal forebrain, amygdala, and entorhinal cortex than patients with early PD and controls. Across all patients with PD, the gray matter density in nearly all subcortical regions significantly decreased with disease duration. These findings suggest an organized pattern of atrophy across disease progression.Black et al. proposed a novel phMRI method for objectively quantifying disease severity in PD. Specifically, the authors proposed a method to measure the effect site rate constant and the predicted time using phMRI, based on the timing of the known response of several brain regions to exogenous levodopa. This new method will enable measurement of the severity of dopamine denervation objectively and will simultaneously provide a robust imaging response to exogenous levodopa.Matsuura et al. examined pulvinar thalamic hypointensity in 21 patients with PD who underwent deep brain stimulation (DBS) at baseline and 1 year after using SWI. Pulvinar hypointensity was identified in 11 of the 21 patients at baseline. One year after DBS, pulvinar hypointensity was found in five of the six patients who had worsened cognitive performance, and in all six patients who had hallucinations. These findings, i.e., pulvinar hypointensity in patients after DBS, are helpful for detecting cognitive worsening and the emergence of hallucinations.Aljuaid et al. studied the effects of anti-parkinsonian medications in 10 patients with PD (5 with LID and 5 without LID), using FDG-PET and perfusion MRI in their ON and OFF states. The study found a significant interactive effect in putamen, in which glucose metabolism was consistently decreased by anti-parkinsonian medication, while mixed effects were observed in CBF perfusion. Furthermore, the putamen-to-thalamus PHI may be a potential biomarker for LID.Patients with PD and LID often present increased cerebral blood flow and decreased putaminal metabolism. Neuroimaging studies have provided new insights into the distinct characteristics of brain activity, midbrain atrophy, dysconnectivity, and metabolic alterations associated with PD. These studies have highlighted the potential of neuroimaging in detecting PD-associated motor and non-motor symptoms such as freezing of gait (FOG), depression, and cognitive dysfunction.Li et al. evaluated motor asymmetry in PD using amplitude of low-frequency fluctuation (ALFF), assessed with resting state fMRI (rs-fMRI). The study found altered ALFF in patients with left-onset PD (LPD) compared with a control group. ALFF of the left inferior temporal gyrus correlated with motor function, and ALFF of the thalamus correlated with cognition. These findings provide new insights into the distinct characteristics of spontaneous brain activity in LPD.Droby et al. reported midbrain atrophy in patients with PD and FOG compared with those without FOG. Furthermore, decreased midbrain-cortical FC was found to be associated with FOG occurrence and the severity scores of patients with PD.Using multi-modal analyses with voxel-based morphometry and functional connectivity (FC), Jin et al. analyzed structural and functional connectivity using FA and MD measurements from DTI and voxel-mirrored homotopic connectivity (VMHC), calculated from rs-fMRI images of 24 patients with PD and FOG+, 37 patients with PD and FOG–, and 24 healthy controls. Patients with PD and FOG+ had impaired interhemispheric brain connectivity, measured by FA, MD, and VMHC, which was related to clinical FOG severity. These results demonstrate that integrating structural and functional MRI analyses can provide information on the pathophysiological mechanisms of FOG in PD.To reveal the dysconnectivity mechanism underlying PD with and without freezing of gait, Wang et al. studied brain blood-oxygen-level-dependent (BOLD) activities using Regional Homogeneity (ReHo), calculated from rs-fMRI. The authors reported that mildly-moderately depressed PD had a lower ReHo in the anterior cingulate cortex than that for non-depressed PD. Severely depressed PD had a higher ReHo in the frontal area than that for mildly-moderately depressed PD. Severely depressed PD had a higher ReHo in the supplementary motor area than that for non-depressed PD. ReHo measurement may provide evidence for the prediction of PD with subclinical depression.Guan J-t. et al. used 1H-MRS to investigate the alteration of metabolites in patients with PD at different stages of the disease. The results revealed that altered metabolites are associated with non-motor symptoms, including sleep and gastrointestinal and cognitive dysfunction in patients with PD at late stages, suggesting that these metabolic markers may be able to track disease progression in PD.Atypical Parkinsonism shares typical motor symptoms with sporadic PD, and misdiagnosis is frequent. Measuring neuromelanin-sensitive signals as well as structural indices of the brainstem, cerebellum, midbrain, and basal ganglia nuclei help differentiate corticobasal syndrome (CBS), PSP, and MSA from PD. Tau-PET and DAT imaging have shown strong effects in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD).Picillo et al. performed midbrain-based MRI morphometric assessments in 67 patients with PSP. The study reported that reduced midbrain size is significantly associated with greater ocular motor dysfunction at baseline MRI as well as more rapid disease progression upon follow up.Vasilevskaya et al. compared parkinsonian syndromes (CBS/PSP) without AD biomarkers  to parkinsonian syndromes with AD biomarkers , using MRI and PET imaging with a tau ligand [18F]-AV1451 tracer. The AD biomarker–positive group had increased Tau-uptake and lower volumes in AD-specific areas. These results suggested that CBS and PSP syndromes are strongly affected by the presence of AD biomarkers.Talai et al. compared the accuracy of using multi-modal MRI datasets for automatic differentiation of patients with PD, patients with progressive supranuclear palsy Richardson's syndrome (PSP-RS), and healthy controls. Machine learning models showed that regional DTI metrics performed excellently, with a 95.1% classifying accuracy, similar to the optimal multi-modal machine learning model. These uni-modal DTI and multi-modal  datasets may provide useful markers in differentiating PD and PSP-RS.Kanetaka et al. studied CIS using IMP-SPECT in patients with mild cognitive impairment (MCI), AD, or DLB. The CIS score in the AD group was significantly higher than that in the DLB or MCI groups. The results suggest that the diagnostic power of IMP-SPECT is not inferior to that of ECD-SPECT in differentiating DLB from AD.The cingulate island sign (CIS), which is a preserved pattern in the posterior cingulate gyrus on FDG-PET, is an important sign to distinguish DLB from AD. Inagawa et al. investigated the efficacy of olfactory and hallucination tests in differentiating AD from DLB, in comparison with the known biomarkers for DLB, including DAT-SPECT and meta-iodobenzylguanidine (MIBG) in myocardial scintigraphy. Their results suggest that the hallucination and olfactory tests may be considered before resorting to nuclear neuroimaging in the diagnosis of DLB.In conclusion, this Research Topic provided articles on well-established and emerging neuroimaging biomarkers to improve diagnostic certainty and to ensure more precise treatment strategies. A remarkable advantage is the integrative multimodal neuroimaging approach, which proved superior to single modality-based methods. We hope that readers will find this Research Topic a useful reference for state-of-the-art neuroimaging developments and applications in Parkinson's Disease and Parkinsonism.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Monitoring pests is a labor-intensive and time-consuming task for agricultural experts. This paper proposes a new approach to classifying and counting different categories of crop pests. Specifically, we propose a multi-category pest detection network (MCPD-net), which includes a multiscale feature pyramid network and a novel adaptive feature region proposal network. The multiscale feature pyramid network is used to fuse the multiscale pest information, which significantly improves detection accuracy. The adaptive feature region proposal network addresses the problem of not aligning when region proposal network (RPN) iterating, especially for small pest objects. Extensive experiments on the multi-category pests dataset 2021 (MPD2021) demonstrated that the proposed method provides significant improvements in terms of average precision (AP) and average recall (AR); it outperformed other deep learning-based models.Specialized pest control for agriculture is a high-priority agricultural issue. There are multiple categories of tiny pests, which pose significant challenges to monitoring. Previous work mainly relied on manual monitoring of pests, which was labor-intensive and time-consuming. Recently, deep-learning-based pest detection methods have achieved remarkable improvements and can be used for automatic pest monitoring. However, there are two main obstacles in the task of pest detection. (1) Small pests often go undetected because much information is lost during the network training process. (2) The highly similar physical appearances of some categories of pests make it difficult to distinguish the specific categories for networks. To alleviate the above problems, we proposed the multi-category pest detection network (MCPD-net), which includes a multiscale feature pyramid network (MFPN) and a novel adaptive feature region proposal network (AFRPN). MFPN can fuse the pest information in multiscale features, which significantly improves detection accuracy. AFRPN solves the problem of anchor and feature misalignment during RPN iterating, especially for small pest objects. In extensive experiments on the multi-category pests dataset 2021 (MPD2021), the proposed method achieved 67.3% mean average precision (mAP) and 89.3% average recall (AR), outperforming other deep learning-based models. Crop yields play an essential role in agricultural economic development. However, agricultural pests significantly affect crop production. Traditional pest recognition usually depends on manual observation by agricultural experts, whose work is subjective and labor-intensive ,2,3. ThePrevious studies on pest recognition focused on conventional machine learning methods. They used image processing and machine learning approaches to extract pest features and then classify them. Gassoumi et al.  proposedRecently, some approaches based on deep convolution neural networks (DCNNs) have shown excellent performance on various vision tasks, including image classification, object detection, and object tracking. Object detection methods can be roughly divided into one-stage methods and two-stage methods. One-stage methods, such as the single shot multibox detector (SSD) , you onlThe main limitations to its successful application are as follows: (1) The sizes of pests are diverse; some large pests are hundreds of times larger than small pests b,c. (2) In this work, to address these problems, we propose a multi-category pest detection network (MCPD-net). First, a multiscale feature pyramid network (MFPN) for feature extraction is designed to obtain different scale information of pests. To obtain an enhanced feature pyramid network, an adaptive channel fusion module (ACFM) and a global context module (GCM) are introduced to capture recognizable multiscale contextual information to improve the detection accuracy for pests with diverse sizes, especially small pests. Second, an adaptive feature region proposal network (AFRPN) is proposed to obtain richer features with detailed information of pests. To alleviate the disturbances from complex backgrounds, a feature adaptation module (FAM) and a two-stage RPN method are introduced to correctly locate and classify pests. Third, we created a large-scale dataset named the multi-category pests dataset 2021 (MPD2021), containing 18,595 crop pest images with 26 categories and 125,700 specimens. Finally, with the MPD2021 dataset, extensive comparison experiments showed that our new model achieves 67.3% mean average precision (mAP) and 89.3% average recall (AR), which significantly outperforms other state-of-the-art methods.To sum up, this work makes the following contributions:(1) A large-scale dataset named MPD2021 was built, which will promote the effectiveness of applications of new object detection approaches in intelligent agriculture.(2) A end-to-end detection method named MCPD-net is presented to detect large-scale pest images. The MFPN in MCPD-net can handle pests of various sizes, which significantly enhances the detection performance for multiscale pests.(3) The presented AFRPN is able to solve the problem of anchor and feature inconsistency during the training iteration process, which benefits pest location and classification.The rest of the paper is organized as follows: Some DCNN-based approaches have been developed to solve the pest detection tasks ,20,21,22FPN-based object detectors fuse multiscale features in a top-down and lateral connection manner to build a feature pyramid ,24,25. TRegion proposal networks (RPN) are frequently used in two-stage detectors. They are used to generate a sparse set of proposal boxes by adjusting the anchors. Traditional methods adopt selective search (SS)  and EdgeThe appearance and main internal structure of the light trapping device for pest monitoring are shown in To promote the development of the field of automatic pest monitoring, some open datasets have been published so researchers can train models, such as IP102  and the Spodoptera frugiperda (category 26) and Proxenus lepigone (category 7), respectively. The average width of pests ranges from 37 to 215 pixels, and the average height ranges from 35 to 211 pixels. All categories have a relative scale of less than 0.9%; the smallest average relative scale is only 0.0282%. As the MPD2021 dataset has a large number of small objects with poor feature information, this will cause significant challenges for network localization and accurate recognition.Pleonomus canaliculatus (category 23) and Spodoptera frugiperda (category 26). To further analyze the scale problem, we analyzed the distribution of pest objects’ relative scale, as reported in To further analyzing the distribution of specimens in MPD2021, the distribution of specimens and relative scales are shown in The overall architecture of MCPD-net is shown in Some researchers developed detection approaches to address the challenges of multiscale features with different spatial resolutions. Following the setting of FPN , featureAdaptive Channel Fusion: To appropriately achieve feature fusion, we fully leverage the relationships between the feature maps. Let Global Context: Detection performance and stability can be improved by exploiting global context information. Therefore, a global context module is introduced to strengthen MFPN. This module is integrated after the ACFM, as shown in a consists of a set of four-dimensional information a to the ground-truth box g, as follows:The detection problem is formulated in Faster R-CNN as a two-step procedure. The RPN is first used to generate a sparse set of proposal boxes by adjusting a set of anchors. The proposal boxes generated by the RPN are then refined and classified by a regional CNN detector. RPN is designed to extract high-level features and predict proposals in an end-to-end way. For a feature map The regressed anchors on (NMS)  to generFeature Adaptation: The previous method adopts standard two-dimensional convolution to sample the feature map F in a regular grid l on the output feature y. However, in AFRPN the offset field y will be volution  that repTwo-stage RPN: A two-stage process is proposed to align anchors to features in the RPN stage. That is, the conventional convolution is used to maintain the spatial features in the first stage. In the following stages, the offset Equation . In the This section has a brief description of the evaluation metrics, training parameters, experimental details, and results of experiments on the constructed MPD2021 dataset.Several evaluation metrics are used to evaluate the effectiveness of different approaches in the multi-category pest dataset. Average precision (AP) and mAP are used as the main evaluation metrics. AP is the area bounded by the precision–recall curve. In addition, In MCPD-net, the backbone network is Resnet-50, which was pretrained on the ImageNet  dataset. toolbox . All expIn this section, the performance of MCPD-net is first compared with those of the state-of-the-art object detectors. Then, extensive ablation experiments on the MPD2021 dataset are reported to validate the effectiveness of the proposed module in MCPD-net. The testset in the MPD2021 dataset contains 3719 pest images. Nilaparvata lugens (category 1) seemed to be the most difficult to detect and had the lowest AP, 28.8%. Almost all models could successfully detect Gryllotalpa orientalis (category 22) with 94.0% AP. This is because tiny pests make it more difficult to extract effective features than larger pests. Furthermore, about 12 categories had over 70% detection accuracy, and the accuracy of almost all pest categories increased by using MCPD-net. The detection results for small pests Nilaparvata lugens, Plutella xylostella, Cnaphalocrocis medinalis, and Melanotus caudex  showed different degrees of improvement.There are significant differences in the results for specific categories, as shown in (a) Baseline setup: The baseline network is driven by Faster R-CNN with the backbone ResNet-50. It can be seen in Nilaparvata lugens (category 1) was only 16.5%.(b) Effect of MFPN: It can be seen in (c) Effect of AFRPN: There are many easy negative samples during the training stage, which can lead to poor results. The AFRPN was proposed to solve this problem. As shown in Some visualization analyses were conducted to evaluate the proposed MCPD-net. As shown in The positive anchor samples in AFRPN are illustrated in China is a large agricultural country. The main crops grown include rice, wheat, corn, etc. However, these crops are prone to reduced quality and yield of products due to crop pests. The widespread application of chemical pesticides has become an important means to prevent and control crop pests. However, farmers often tend to blindly use pesticides in large quantities when they cannot accurately identify pests, which can cause ecological environmental pollution and soil contamination. Thus, agricultural experts with professional knowledge are badly required to help them recognize pests. However, traditional pest recognition is usually labor-intensive and time-consuming. Intelligent light trapping devices can automatically attract many species of pests and capture images, which greatly reduces the workload of these experts. Although in practical applications, light trapping devices also attract trap pollinators and beneficial insects, the number of devices deployed is not large, so it will not have a huge impact on the environment. The collected images will be sent to a cloud server for analysis and monitoring. We proposed an object detection method named MCPD-net to automatically monitor multiple categories of pests to replace the manual observation method.The proposed detection method can detect 26 categories of widespread agricultural pests see . When coNilaparvata lugens (category 1) and Plutella xylostella (category 12), the detection results were only 28.8% AP and 35.6% AP, which are worse results than for other categories. They are too small, occupying only 0.0282% and 0.0545% pixels of the entire image. Our future work will aim to improve the detection accuracy for tiny pests.Our next research goal will be to further extend the number of pest categories in the dataset. This will support farmers to precisely apply chemical pesticides to protect the field from further damage. Although MCPD-net has achieved excellent experimental results, it still needs to be improved. For example, for In order to replace manual recognition methods with computer vision methods for automatic monitoring of pests in crop fields, we proposed a novel end-to-end method named MCPD-net that can be applied to detect 26 species of crop pests. MCPD-net consists of an MFPN for obtaining multiscale pest features, and the novel AFRPN makes the anchor box and features consistently. Extensive experiments were conducted on the MPD2021 dataset. MCPD-Net achieved 67.3%


Prurigo nodularis (PN) is a dermatological condition characterized by nodular hyperkeratotic lesions mainly on the legs and arms. Asymmetrical PN is a rare dermatological condition often associated with paralysis and stroke. In this paper, we present the case of a 77-year-old woman who developed post-ictal PN which responded to dupilumab, an anti-interleukin-4/13 drug approved for the management of AD, with an extreme reduction in itch sensation. Dupilumab and other therapies reducing Th2 inflammation may, in the future, become an alternative treatment for post-ictal pruritus/PN nonresponding to traditional therapies. Of course, larger studies will be necessary to confirm our case’s findings. Neuropathic itch (NI) recognizes multiple etiologies deriving from the peripheral nervous system . CentralA 77-year-old woman presented to our dermatological center with a 2-year history of severe itch associated with thick nodules in the right side of the head, trunk, and right upper limb. At the cutaneous examination, the left side of the body was completely spared. The patient judged her itch intensity as 9/10 on a numerical rating scale (NRS) . The patPruritus is a rare post-stroke symptom whose underlying pathophysiology overlaps with the most common post-stroke pain . NI mighIn conclusion, we may state that dupilumab showed its effectiveness in the management of stroke-associated PN and that it, as with other biologic drugs acting on Th2 inflammation, may retain an effect on various types of neuropathic itches. Of course, prospective studies and clinical trials will be necessary in order to confirm the result obtained in our patient.


Background: Cardiovascular diseases (CVD) are predominantly lifestyle related. Mental health issues also influence CVD progression and quality of life. Self-management of lifestyle behaviors and mental well-being may play a significant role in reducing the CVD burden. Previous studies have shown that mindfulness practices are associated with psychological well-being, but their effects on CVD self-management are mainly unknown. Methods: The study had a before–after design and included adults over 50 years with CVD and/or one or more risk factors from three European countries. Follow-up was six months. The intervention was a 7-week mindfulness-based intervention (MBI) in a group setting focusing on chronic disease self-management. Outcomes were measured with validated self-report questionnaires at baseline and follow-up: self-efficacy, physical activity, nutrition, smoking, alcohol use, sleep and fatigue, social support, stress, depression, medication adherence, and self-rated health. Results: Among 352 participants, 324 (92%) attended ≥4 of the 7 group sessions and completed follow-up. During follow-up, self-efficacy, stress, social support, depressive symptoms, and self-rated health significantly improved. No significant changes were detected for other outcomes. Conclusions: A 7-week MBI focusing on chronic disease self-management was conducive to improved self-efficacy, emotional well-being, social support, and self-rated overall health during six months. These findings support the use of MBIs for improving self-management in cardiovascular care. ISRCTN registry-number ISRCTN11248135. Despite substantial improvements in outcomes in recent decades, cardiovascular diseases (CVD) are still the leading causes of morbidity and mortality globally, with an estimated 17 million deaths each year [Much of the global burden of CVD is attributable to uncontrolled behavioral risk factors, including poor diet, physical inactivity, and smoking . In addiOne such intervention target is mindfulness, commonly defined as moment-to-moment awareness of one’s experience without judgement . MindfulAlthough preliminary research suggests that mindfulness may influence blood pressure and glycemic control, the potential of mindfulness training in facilitating self-management of CVD has received limited attention . TherefoThe SEFAC study had a before–after single-group design and was conducted between 28 November 2018 and 26 October 2020 in 4 European countries , and the Netherlands). For full details of study design and protocol, see Zhang et al.  ISRCTN rRecruitment for participation in a study investigating a new intervention to improve the self-management of chronic cardiovascular diseases through mindfulness training, social engagement, and e-health support was conducted in the study sites . Community-dwelling citizens were recruited using public events and announcements, patient and volunteer organizations, and social media. Main eligibility criteria were age over 50 years and established CVD  and/or one or more risk factors for the development of CVD . In addition, citizens were not eligible to participate in the study when they were diagnosed with mild or severe cognitive impairment, were terminally ill or scheduled to enter secondary or tertiary care settings for a long period, not able to comprehend the information provided in the local language, or not able to make an informed decision regarding participation in the study. The SEFAC intervention to promote health behaviors and psychological well-being had a duration of 7 weeks, and consisted of three elements, (i) weekly mindfulness-based sessions for seven weeks, (ii) support by social engagement, and (iii) e-health support by the SEFAC app . Ad (i): The mindfulness-based sessions were offered in a series of seven weekly in-person group sessions (11–12 participants), lasting 2–2.5 h each for which a workbook was available. The sessions focused on mindset, habit change, relationships, and living with chronic conditions and included elements of positive psychology and health coaching in addition to mindfulness training. They were conducted by certified mindfulness professionals and/or health care professionals with training in mindfulness. Furthermore, local volunteers facilitated the intervention during and between the sessions in terms of logistics, raising awareness for self-management, motivating participants to commit to the intervention, and assisting them with e-health support. The intervention incorporated the core elements of the standard MBSR protocol: (a) mental and physical mindfulness exercises : Social engagement was used to support the mindfulness-based sessions . VolunteAd (iii): In addition to the weekly sessions, participants were encouraged to engage in the practices (described in Outcomes were obtained through self-report questionnaires at the start of the first session (baseline) and at 6-month follow-up to assess the ‘mid-term’ effects , as suggested by Ory et al. and Barkan et al. ,20. The Sociodemographic characteristics , BMI (body mass index), and the presence of chronic conditions were assessed by self-report questionnaires. Good adherence to interventions was defined a priori as attending ≥4 of 7 group sessions . The satThe power considerations of the study were described previously . It was d within-group effect size was computed for all significant outcomes [t-test for continuous outcomes and a z-test for dichotomous outcomes (see p = 0.05/20 = 0.0025. Participant characteristics were described using mean (SD) or number of participants (%) for the total study sample. The effects of the intervention were assessed in the participants who completed the baseline and follow-up questionnaires and attended ≥4 sessions. A paired samples t-test was performed to assess the effects of the intervention on continuous outcome measures. Cohen’s outcomes . For dicomes see . We did n = 147); Treviso, Italy (n = 97); Rotterdam, the Netherlands (n = 84). At the pilot site in the UK (n = 91), outcome measurements with the self-report questionnaires were not feasible because of a high prevalence of health literacy problems; hence, these participants were not included for further analyses. Between 28 November 2018 and 20 February 2020, 352 participants who fulfilled the inclusion criteria provided informed consent and started the intervention; 77 (21.9%) with a history of CVD and 275 (78.1%) at increased risk of CVD due to the presence of one or more risk factors. Participants were included in 3 European study sites: Rijeka, Croatia (n = 352), 343 (97.4%) attended four or more of the seven group sessions. A median of 6 out of 7 group sessions  were attended. The number of participants taking part in the 6-month follow-up assessment was 327 (92.9%). Overall, 324/352 participants (92.0%) completed the baseline and 6-month follow-up questionnaires, attended ≥4 sessions, and were included as the study sample for further analyses. Baseline characteristics of the 28 dropout participants were not significantly different from the included participants, except for the study site. The participant flow chart is shown in Of all included participants (p < 0.0025). Over time, no significant changes were observed for nutrition, physical activity, substance use, sleep, medication adherence, or mental and physical HR-QoL. Of those completing the questions on satisfaction with the intervention at the 6-month follow-up, participants reported that the intervention improved self-awareness (84.8%) and stimulated them to work on a healthy lifestyle (85.4%). The average satisfaction score was 8.2 ± 1.6 on a scale from 1 (lowest) to 10 (highest). The majority of participants (75.0%) perceived the SEFAC app as supportive of a healthy lifestyle through mindfulness exercises. See . One parThis multicenter study involving over 300 individuals with or at increased risk of CVD showed modest effects from a 7-week MBI on self-efficacy, stress, depressive symptoms, social support, and self-rated overall health. The SEFAC MBI was primarily designed to enhance self-management as an approach to improving health behavior and well-being for individuals with or at increased risk of CVD. Self-efficacy, defined as the belief that one has the ability to accomplish a specific task or reach a goal , is consDespite widespread awareness that behavior change is key to the prevention and treatment of CVD, it remains challenging to change behavior . TheoretParticipation in the SEFAC MBI promoted psychological well-being, including reducing perceived stress, less depressive symptoms and better self-rated overall health. Previous meta-analyses demonstrated comparable small-to-moderate beneficial effects for MBIs on stress, depression, anxiety, and quality of life in individuals with a range of chronic conditions ,12. PsycPrevious studies have indicated that social isolation is a risk factor for the poor prognosis of individuals with cardiovascular disease. Isolated and lonely persons have a 1.5-fold increased risk of myocardial infarction, stroke and death . Most ofOne of the strengths of our study is that it was conducted in multiple European study sites with heterogeneous populations of middle-aged and older adults with representative cardiovascular risk profiles. The results suggest that the SEFAC MBI applies to a broad range of individuals with or at increased risk of chronic CVD. The statistical power of the study was considered sufficient; instead of 360 participants, data of 352 and 324 participants were analyzed. Because of the limited sample sizes per study site, we could not generalize about differences in the effects of the MBI among the different study sites. Only about 10% of participants were lost to follow-up, which is a low dropout rate compared to similar behavioral interventions. Dropped out participants were not different from those with complete follow-up in terms of baseline characteristics, making attrition bias less likely.This study has several limitations. First, due to the lack of a control group, it cannot be ruled out that the observed changes are due to nonspecific effects unrelated to the intervention, including attention, expectations for improvement, social support and sense of community deriving from participation in a group-based intervention. Furthermore, although our MBI was based on and included the mindfulness exercises of the well-tested MBSR curriculum, mindfulness itself as a psychological construct was not assessed in this study. All outcome measures were self-reported, which may be less accurate than objectively measured outcomes. In addition, we cannot exclude the presence of a selection or social desirability bias. Our mindfulness-based intervention lasted seven weeks, unlike other existing programs that last eight weeks. However, the SEFAC mindfulness-based intervention took place in relatively small groups, with a similar duration as the MBSR and MBCT; therefore, the intensity of the intervention was assumed to be relatively high. Nevertheless, we recommend that future studies consider possibilities to strengthen the intervention, including making it last eight weeks. In addition, for future studies with larger varied samples, we advise exploring the differences regarding the effects between subgroup participants with cardiovascular disease and subgroup with participants at risk of cardiovascular disease. We recommend future studies to apply a randomized controlled trial (RCT) with pre-defined primary and secondary outcomes. This study only evaluated the ‘mid-term’ effects of the intervention after six months; we recommend future studies to measure both ‘immediate’ effects after finishing the intervention , and the ‘mid-term’ effects after six months. In our study, three scales showed a Cronbach’s Alpha <0.70; we recommend that future studies pay attention to the reliability of the measurements. Moreover, an intervention such as the current one that is applied only one time might have been too short since changing lifestyle patterns is complex and requires continuous attention, practice, and support. Finally, the predefined 6-month follow-up period may have been too short to assess the durability of the observed effects. In conclusion, the present study shows promising effects of a mindfulness-based intervention, in combination with social engagement and e-health support. It enhances self-management as a complementary approach for modifying psychosocial factors relevant to cardiovascular care. Our findings deserve further study in a larger, long-term randomized controlled trial to explore the potential of mindfulness training in catalyzing chronic disease self-management. An intervention offering access to high-quality therapeutic lifestyle interventions focusing on nutrition, physical activity, and substance use, in conjunction with ongoing encouragement for mindfulness practice with digital and community resources, may be a sustainable approach for promoting cardiovascular health.


Process macro in SPSS was used to analyze the single and chain mediating effect among variables. Our findings showed that the indirect and total effect of HIV-related stigma on HIV self-management was significant, while the direct effect was not statistically significant. Social support and self-efficacy mediated the relationship between HIV-related stigma and HIV self-management, respectively. Moreover, the chain mediating model confirmed that the association between HIV-related stigma and HIV self-management was mediated by social support and self-efficacy sequentially. Future interventions focusing on improving HIV self-management among MSM living with HIV should consider a multi-faced approach.HIV infection becomes a manageable disease, and self-management is one of the key indicators of achieving optimal health outcomes. Men who have sex with men (MSM) living with HIV face many psychosocial challenges when managing HIV infection, such as sexual minority pressure and HIV-related stigma. Higher perceived HIV-related stigma had been related to low self-management. However, the mechanisms underlying the association between HIV-related stigma and HIV self-management are unclear. Two possible mediators include social support and self-efficacy. This study aimed to examine the relationship between HIV-related stigma and HIV self-management among MSM living with HIV and to explore the single mediating effect of social support and self-efficacy and the chain mediating effect of these two variables on this relationship in China. Convenience sampling was used to recruit participants from the Center for Disease Control (CDC) in Changsha City, Hunan province, China. A total of 459 MSM living with HIV completed questionnaires regarding sociodemographic and disease-related information, HIV-related stigma, social support, self-efficacy, and HIV self-management. Descriptive statistics analysis, one-way ANOVA, independent  With the introduction and widespread use of antiretroviral therapy (ART) to decrease viral loads and prevent the HIV epidemic, HIV infection has become a manageable chronic disease . HoweverSince the beginning of the HIV epidemic, PLWH have experienced various forms of HIV-related stigma, especially among marginalized groups such as MSM. There is a growing body of conceptual frameworks indicating that perceived HIV-related stigma decreases MSM living with HIV in getting appropriate treatment . PreviouSocial support might be a potential mediator in explaining how HIV-related stigma may lead to poor self-management. However, few studies have investigated whether social support operates as a mediator for the negative effects of HIV-related stigma on HIV self-management. According to the IFSMT , improviSelf-efficacy might be another potential mediator explaining the pathway from HIV-related stigma to HIV self-management. On the one hand, HIV-related stigma and self-efficacy are closely related. As we hypothesized, social support and self-efficacy mediate the relationship between HIV-related stigma and HIV self-management. However, when they were both considered to be mediators, what was the relationship between social support and self-efficacy? Which one played a more critical moderating role? According to the IFSMT , social In summary, although the relationships among the variables of stigma, social support, self-efficacy, and health behaviors have been examined separately, the role of social support and self-efficacy in the impact of HIV-related stigma on HIV self-management among MSM living with HIV has not yet been thoroughly tested to date. Hence, we used IFSMT as the framework to test the relationship between HIV-related stigma and HIV self-management and the mechanical roles of social support and self-efficacy among MSM living with HIV. Based on previous research, we proposed three main hypothesized models :Hypothesis 1: HIV-related stigma might have a negatively predictive effect on HIV self-management.Hypothesis 2: Social support would act as a mediator between HIV-related stigma and HIV self-management.Hypothesis 3: Self-efficacy would act as a mediator between HIV-related stigma and HIV self-management.Hypothesis 4: Social support and self-efficacy would jointly act as a chain mediating role in the relationship between HIV-related stigma and HIV self-management.This cross-sectional study was conducted from October 2021 to January 2022. By convenience sampling, all participants were recruited from the Center for Disease Control (CDC) in Changsha City, Human Province, China. A set of self-reported questionnaires were used to collect data. A total of 473 questionnaires were distributed, of which 459 questionnaires were valid. Fourteen questionnaires (3%) were excluded due to participants dropping out in the middle of the process, resulting in an efficiency of 97.0%. The inclusion criteria were: (a) men meeting the Chinese Ministry of Health’s diagnostic criteria for HIV; (b) self-reported ever having sex with another man within the last 6 months; (c) 18 years or older; (d) provided informed consent; and (e) volunteered freely for the study. We asked a couple of questions to assess participants’ eligibility and excluded those with a severe mental disorder and linguistic or cognitive impairment.The Ethics Committee approved all the study procedures of XXX. Participants were recruited by convenience sampling when they came to the AIDS department of CDC to get HIV health counseling or services. Four trained CDC staff introduced our project to the potential participants, and if they were willing to join this study, they were contacted and invited by the trained investigators. Before the investigation, the investigators explained the study’s purpose, content, significance, and potential risks to the participants. All participants provided written informed consent and voluntarily participated in the study. Subsequently, the investigators distributed paper-based questionnaires and explained the filling requirements to the respondents. All questionnaires were self-reported, and participants completed them independently in a private and quiet room to ensure privacy. A face-to-face interview was used for patients with limited reading ability to help them complete questionnaires.The research team designed the demographic survey to gather participants’ demographic information including age, educational level, residence, marital status, and monthly household income. HIV-related information, including HIV infection route, years of HIV diagnosis, comorbidities, and drug side effects, was also collected.The HIV Self-management Scale (HIVSMS) developed by HIV-related stigma was assessed using a brief version of Berger’s Stigma Scale (HSS), which was developed by Social support was assessed using the Social Support Rating Scale (SSRS), initially designed in Chinese by Self-efficacy was measured using the Self-efficacy for Managing Chronic Disease Scale (SEMCDS) compiled by M) and standard deviation (SD). One-way ANOVA and independent t-tests were used to examine the differences in HIV self-management among sociodemographic characteristics and disease-related factors. Multiple linear regression analysis was conducted to further explore the associated factors if they had statistical significance in univariate analysis. Pearson correlation analyses were performed to examine whether there is a correlation between HIV stigma, social support, self-efficacy, and HIV self-management.Descriptive statistics of sociodemographic and disease-related characteristics and variables of interest were reported. Frequency and percentage were used to describe categorical variables. Continuous variables such as scale total scores were reported on the mean (p of 0.05 (two-tailed) was considered statistical significance. All the data analyses and processing were completed using IBM SPSS v24.0 software.The direct and indirect effects of HIV-related stigma on HIV self-management were examined using bootstrap analyses with 5,000 bootstrap samples . AdjustiDue to a single source of data, Harman’s single-factor test was used to reduce the common method biases. The results revealed 13 factors with an eigenvalue greater than 1, and the total variation explained by the first factor was 16.73%, which was far lower than the critical value of 40%. Thus, there were no apparent common method biases in the data.SD = 8.64, range: 18–76). The total HIV self-management score was 39.60. Monthly household income, infection route, comorbidities, and drug side effects were significantly associated with HIV self-management in univariate analyses. The multiple linear regression analyses included all the significant variables found in univariate analyses, that comorbidities and drug side effects were statistically significantly associated with HIV self-management, and were included in the single and chain mediation models as covariates. Participants with comorbidities or drug side effects reported a lower level of HIV self-management.r = −0.338, p < 0.001), lower self-efficacy , and lower HIV self-management . Higher social support was correlated with higher self-efficacy  and better HIV self-management . Higher self-efficacy was correlated with better HIV self-management .As shown in β = −0.359, p < 0.001), and higher social support predicts better HIV self-management , and higher self-efficacy predicts better HIV self-management  was slightly higher than self-efficacy (−0.095), social support was a stronger mediator than self-efficacy.In the model with self-efficacy as the mediator, lower HIV-related stigma predicts higher self-efficacy  and self-efficacy . Social support  and self-efficacy  directly and significantly predict the status of HIV self-management. Meanwhile, social support can also directly and significantly predict self-efficacy  and − 0.046 , respectively. The bootstrap’s 95% CI did not overlap the zero, indicating the two indirect pathways were statistically significant. Importantly, supporting our hypotheses, the indirect effect of chain mediation from HIV-related stigma to HIV self-management via social support and self-efficacy was significant, and the effect value was −0.024 . In conclusion, the results mean that social support and self-efficacy play a full mediating role in the relationship between HIV-related stigma and HIV self-management. The chain mediation model is shown in Results of the chain mediation analyses in The present study explored the mediating role of social support and self-efficacy on the association between stigma and HIV self-management among MSM living with HIV based on the IFSMT. The results of parallel mediation analyses supported the hypotheses and confirmed the mediating role of social support and self-efficacy in the relationship between HIV-related stigma and HIV self-management. In addition, the chain mediation analyses suggested a significant serial between social support and self-efficacy.In this study, the level of HIV self-management was higher than that found in general Ethiopian PLWH , and lowThe current study also showed that higher HIV-related stigma was associated with a lower level of HIV self-management among MSM living with HIV after controlling comorbidities and drug side effects, which is obviously consistent with our first hypothesis and previous studies . For insvia social support. A previous study conducted by In line with our second expectations, the present study’s finding suggested that HIV-related stigma could work on HIV self-management Consistent with the third hypothesis, decreasing HIV-related stigma may lead to a higher level of self-efficacy, which can positively impact behaviors. Our finding is congruent with a published study indicating that individuals with less internalized stigma were tend to be with more self-efficacy in adhering to ART, which facilitates them in conducting better HIV self-management regarding taking medicines . HIV-relFurthermore, our most notable finding is that HIV-related stigma had an impact on HIV self-management through the chain mediation of social support and self-efficacy, namely individuals with less stigma would firstly perceive more social support and then increase self-efficacy, which promotes their HIV self-management finally. This result supports our hypotheses and expands upon existing researches indicating that social support provides the necessary tools and information to assist patients in developing the skills to increase their confidence and regularly contact the healthcare system to address problems . Cabral The findings of this study extend our understanding of the status and influencing factors of HIV self-management and reveal ways in which HIV self-management could be improved. This study might have several clinical implications. First, the present study pinpoints the need for interventions to reduce HIV-related stigma. Structural efforts to educate the uninfected population and health providers on the vulnerability experienced by PLWH may reduce social stigma to patients and facilitate their participation in HIV care . EffectiInevitably, several limitations in this study should be acknowledged. First, the current study was a cross-sectional design, which excluded us from capturing longitudinal trends and establishing causality. Future longitudinal studies should be designed to explore causal inferences and further test and verify the reliability of our results . Second,The current study not only explored the mechanism of HIV-related stigma on HIV self-management in a Chinese MSM living with HIV, but also extended the application of IFSMT in the HIV self-management field. These findings indicated that social support and self-efficacy play as both individual mediators and chain mediators in the relationship. Given the mediating effect of social support and self-efficacy on HIV self-management, programs related to social support and self-efficacy should be designed to enhance HIV self-management among MSM living with HIV who report high levels of HIV-related stigma in China and other global settings.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study involving human participants were reviewed and approved by Xiangya Nursing School, Central South University. The patients/participants provided their informed consent to participant in this study.YT, XX, and HW designed the work. YT and XX collected the data. YT, JM, and HW analyzed and drafted the manuscript. YT, XX, JM, and HW revised the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the Provincial Natural Science Foundation of Hunan Grant (2022JJ30769).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


However, significant improvements were noted for AF-specific QoL (p = 0.001), AF knowledge (p < 0.001), medication adherence (p = 0.008), patient satisfaction (p = 0.020), and depression (p = 0004). The preliminary evaluation of the NICE-AF clinic demonstrated the clinical utility of this new model of integrated care in providing safe and effective community-based AF care. Although a full evaluation is pending, the preliminary results highlighted its promising potential to be expanded into a permanent, larger-scale service.The current physician-centric model of care is not sustainable for the rising tide of atrial fibrillation. The integrated model of care has been recommended for managing atrial fibrillation. This study aims to provide a preliminary evaluation of the effectiveness of a Nurse-led Integrated Chronic care E-enhanced Atrial Fibrillation (NICE-AF) clinic in the community. The NICE-AF clinic was led by an advanced practice nurse (APN) who collaborated with a family physician. The clinic embodied integrated care and shifted from hospital-based, physician-centric care. Regular patient education, supplemented by a specially curated webpage, fast-tracked appointments for hospital-based specialised investigations, and teleconsultation with a hospital-based cardiologist were the highlights of the clinic. Forty-three participants were included in the six-month preliminary evaluation. No significant differences were observed in cardiovascular hospitalisations ( Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia, whose spectrum ranges from paroxysmal, self-terminating episodes of electrical disturbance to a chronic condition with clinical sequelae. There is a 20 to 25% lifetime risk of developing AF among adults, and this reported value is similar between Caucasian and Chinese populations worldwide ,2. NeverLong-term outcomes of AF are clinically significant and manifold. Among AF patients, the elevated risk of heart failure and stroke has been found to translate into increased mortality . AdditioAccordingly, international  and regiThe prevention of stroke in the management of AF is complex since it requires frequent monitoring of the patient’s anticoagulation status and consequently the titration of the oral anticoagulation (OAC) dosage. In this context, clinicians have been observed to lack knowledge on AF and, hence, to demonstrate less confidence in making accurate clinical judgements . NonetheWhile physicians may have knowledge about AF and stroke risk assessment in AF patients, such knowledge has not been translated into practical measures for preventing stroke. Physicians, especially non-cardiologist ones, tended not to initiate OAC therapy for AF patients when indicated .Against the background of suboptimal AF management , existing clinician-centric care models based in tertiary hospitals may be unable to address the rising prevalence of AF. This therefore underlines the need for more efficient clinical approaches. Accordingly, an integrated care approach has been recommended by the European Society of Cardiology for chronic AF patients . Such a Advanced practice nursing has a growing presence internationally . The IntAPN-led services across settings have been reported to be safe and exert positive impacts on patient-reported outcomes and clinical outcomes . As alluAF patient-reported outcomes, i.e., AF-related QoL, AF knowledge, medication adherence, patient satisfaction and depression; andAF patients’ clinical outcomes, i.e., cardiovascular hospitalisation and stroke incidence.This study aimed to provide a preliminary evaluation of the effectiveness of the Nurse-led Integrated Chronic care E-enhanced Atrial Fibrillation (NICE-AF) clinic in the community. The specific objectives were to evaluate its effectiveness in improving:The purpose of this preliminary evaluation was to assess if the NICE-AF clinic’s potential for development into a more permanent, larger-scale service.An uncontrolled before-and-after study design was adopted .In this study, the NICE-AF clinic was based in Bukit Batok Polyclinic, which catered to the healthcare needs of residents in western Singapore. This facility was part of an integrated network of public outpatient healthcare centres (collectively known as the Polyclinics) responsible for delivering primary healthcare in Singapore. They provide subsidised medical care, post-hospital discharge medical follow-up care, immunisation, basic diagnostic services, pharmaceutical services, health education, and health screening. Apart from caring for acute illnesses (such as cough and cold) and acute injuries (such as minor fractures), the Polyclinics play a pivotal role in chronic disease management in the primary care setting through their multidisciplinary care teams. Such teams comprise physicians, nurses, and allied health professionals, including dieticians, medical social workers, pharmacists, psychologists, physiotherapists, and podiatrists . APNs arPatients who met the following eligibility criteria were included as newly diagnosed AF, or chronic, stable AF , as docuThey were excluded if they were participating in another clinical study; or had pre-existing complex comorbidities requiring follow-up care by a hospital-based medical specialist; or had undergone cardiac surgery less than three months before recruitment; or were pregnant; or had underlying psychiatric disorders and were under treatment at the time of recruitment; or had cognitive decline or mental incapacitation.Consecutive sampling was adopted to recruit participants. In determining the sample size for this study, reference was made to a keynote Netherlands-based randomised controlled trial, which compared a nurse-led integrated chronic care approach with routine outpatient care for managing AF patients . A hazarParticipants were recruited from the patient registry of Bukit Batok Polyclinic between September 2018 and June 2021. Physicians were encouraged to refer patients with an existing or new diagnosis of AF to the NICE-AF clinic. Upon such referral, they would be screened by the research team for eligibility for the study. However, between January and August 2020, recruitment was suspended in response to the COVID-19 pandemic, as healthcare institutions and the university deferred cross-institutional visits and non-critical research activities.The set-up of the NICE-AF clinic was guided by elements of the Chronic Care Model (CCM)  21]. It. It21]. In this study, the NICE-AF clinic was led by an APN. In the broader context of Singapore, APNs are master’s degree-prepared nurses with collaborative prescribing rights and limited referral and admission privileges ,24. Undewww.nice-af.wixsite.com/livingwithaf) on AF developed by the authors . This online content was available in English and Simplified Chinese and covered AF management, anticoagulation, lifestyle activities, and diet modification. Additionally, the patients under this modality enjoyed fast-tracked appointments for hospital-based specialised investigations, including transthoracic echocardiogram (TTE), Holter studies, or treadmill ECGs. Lastly, consultations with a hospital-based cardiologist were available through telecommunication. The frequency of clinic visits is shown in During NICE-AF clinic consults, the APN delivered regular patient education, aided by a webpage  questionnaire , AF knowThe clinical outcomes, cardiovascular hospitalisation and incidence of stroke, were collected retrospectively (six months before study entry) and prospectively (six months after study entry) from the participant’s electronic medical records.0 and T1): the first administration took place immediately before the first NICE-AF clinic consultation (T0), while the second took place six months after it (T1) (All questionnaires were administered face-to-face over two timepoints (T it (T1) . Descriptive analysis was conducted to characterise the participants’ baseline demographic data and clinical data. The Wilcoxon signed-rank test was used to compare their clinical and patient-reported outcomes six months before recruitment into the NICE-AF clinic with those six months afterwards . In thisApproval was obtained from the National Healthcare Group Domain Specific Review Board (NHG DSRB ref: 2017/00682) for all the research activities involved in this study.Among the 559 patients screened , only 66The socio-demographic profile of the 43 participants is outlined in 2DS2-VASc  score was 3.0 (IQR 2.0–4.0). Their median HAS-BLED  score was 2.0 (IQR 2.0–3.0). Their comorbidities included hypertension (86%), type II DM (40%), ischaemic heart disease (16%), and congestive heart failure (2%).The participants’ clinical profile is outlined in Z = −3.29, p = 0.001) was demonstrated by its AFEQT scores: T1 compared with T0 . Likewise, for AF knowledge, an improvement  was demonstrated by its SGAFKS scores: T1  compared with T0 . At the six-month follow-up, the participants reported significantly higher levels of QoL and AF knowledge than before receiving care at the NICE-AF clinic.Five patient-reported outcomes were investigated . For AF-Z = −2.67, p-value = 0.008) was demonstrated by the single-item questionnaire: T0  compared with T1 . Likewise, for patient satisfaction, an improvement  was demonstrated by its overall PSQ scores: T0  compared with T1 . At the six-month follow-up, the participants reported significantly better medication adherence and patient satisfaction than before receiving care at the NICE-AF clinic.For medication adherence, a statistically significant improvement  was demonstrated by its PHQ-9 scores: T0  compared with T1 . At the six-month follow-up, the participants reported significantly lower levels of depression than before receiving care at the NICE-AF clinic.Lastly, for depression, a statistically significant reduction , although its range decreased from 3 to 0 between timepoints T0 and T1. Likewise, for the incidence of stroke, there was no statistically significant difference . Two clinical outcomes were investigated . For carThis study preliminarily examined the effectiveness of an APN-led AF clinic adopting an integrated care approach towards community-based AF management. Emerging evidence from the results has demonstrated such a new modality could deliver safe and effective care to AF patients. Despite lacking improvements for cardiovascular hospitalisation and stroke incidence, the NICE-AF clinic has evidently contributed to substantial benefits for the numerous patient-reported outcomes.In terms of patient-reported outcomes, the participants’ improved AF-specific QoL at the six-month follow-up at the NICE-AF clinic was reflected by the elevated overall median AFEQT score. Notwithstanding the already high baseline scores, the participants experienced further improvement in AF-specific QoL after receiving care at the NICE-AF clinic. It might be explained by the consistent delivery of patient education and counselling by the same team of healthcare professionals in the NICE-AF clinic about medications, treatment plans, and prevention of adverse events . This haAdditionally, the participants’ improved level of AF knowledge might have been intertwined with their improved AF-specific QoL . PrelimiFor the participants’ medication adherence, the six-month preliminary evaluation likewise demonstrated a significant improvement at the six-month follow-up, despite the high baseline adherence. Besides the patient education and counselling at the NICE-AF clinic, some other socio-demographic factors might have promoted adherence. A large cross-sectional, Singapore-based study has found that older patients  and patients who were married or widowed were more likely to be adherent to their oral medications . They teFor the overall patient satisfaction, a significant improvement was likewise reported. Two underlying reasons might have been at work. Firstly, the consistent delivery of care by the same healthcare providers  might haFor the depression scores, a reduction was reported in the six-month preliminary evaluation of the NICE-AF clinic, representing a significant improvement considering that the participants already had low depression scores at baseline. This finding paralleled that of the landmark randomised controlled trial examining the effectiveness of a nurse-led integrated model of AF management . In the 0 versus 0 at T1) after the NICE-AF clinic. Nonetheless, the difference was not statistically significant . Similarly, the evaluation revealed no statistically significant difference between stroke incidence at six months before attending the clinic and that at six months afterwards. Such findings are echoed in the literature on outpatient nurse-led AF care [Besides the improvements observed in patient-reported outcomes, there were no adverse safety signals in the clinical outcomes as well. Instead, the six-month preliminary evaluation revealed a reduced frequency for cardiovascular hospitalisation  and a median HAS-BLED score of 2 (low to moderate risk for bleeding complications) [One reason for the inability to detect any improvements in cardiovascular hospitalisation and stroke incidences could be that the follow-up period of six months might not have been sufficient. A longer period of observation would have been more propitious if the purposes of the study were not to preliminarily evaluate the clinic. Another reason could be that the participating AF patients were generally stable and only needed low-acuity care. Their low baseline frequency of hospitalisations was reflected by a modest cardiovascular risk: a median CHAcations) . FurtherGiven such modest disease severity, differences in the type of intervention might not exert any acute or immediate influences on clinical outcomes such as hospitalisation . HoweverOn the whole, the positive impacts on the numerous patient-reported outcomes from the NICE-AF clinic have probably arisen from the consistent patient education and counselling by the APN. In general, patient education is inherent in nursing, even in basic preparatory nursing training. Nurses, therefore, have a professional role in patient education and are looked upon to incorporate teaching in most aspects of their practice . TherefoSome limitations of this preliminary evaluation of the NICE-AF clinic are noteworthy. The study was limited by its design, in which the lack of a control group made it difficult to determine the causality between the intervention and the outcomes of interest . The HawFor before-and-after studies, another limitation is the presence of temporal changes. Self-learning occurs naturally for most people. As patients live longer with their chronic conditions, they tend to become better at learning and coping with them over time; such improvement occurs in a manner independent of any interventions . Under aThe NICE-AF clinic, led by an APN, embodied an integrated model of care that represented a shift from hospital-based physician-centric care. The clinic served as a one-stop facility for patients to receive care for AF and common chronic conditions. The preliminary evaluation of the clinic has demonstrated the clinical utility of this new model of integrated care in providing safe and effective community-based AF care. The NICE-AF clinic appeared to exert positive impacts on AF patients’ AF-specific QoL, AF knowledge, medication adherence, patient satisfaction, and depression scores. It also appears to be safe in terms of clinical events. Although a full evaluation is pending, these preliminary results encouragingly suggest its promising potential for development into a more permanent, larger-scale service.


In this study, we investigated the longitudinal changes and predictive value of multiparametric MRI (mpMRI) features of prostate cancer patients receiving Lattice Extreme Ablative Dose (LEAD) boost radiotherapy (RT). Ninety-five mpMRI from 25 patients, acquired pre-RT and at 3 time points following RT were analyzed. Five regions of interest were analyzed, related to tumor, peritumoral, and normally-appearing tissues. We identified significant changes in the imaging parameters following RT in all regions. By using selected features at the four scan points and their differences (Δ radiomics), we were able to build viable predictive models for endpoint biopsy positivity. Our study demonstrates that RT causes significant changes to quantitative imaging features in both tumorous and normally-appearing tissues. Because of the noninvasive nature of the mpMRI, acquiring multiple exams post-RT is feasible to monitor treatment response. Several quantitative imaging features are promising predictors of treatment failure based on post-treatment positive biopsy, a strong marker for clinically relevant endpoints.p-values < 0.005). Pharmaco-kinetic features changed significantly in the GTV at 3-month post-RT compared to baseline. Several radiomics features at baseline and three-months post-RT were significantly associated with endpoint biopsy positivity and were used to build models with high predictive power of this endpoint . Our study characterized the RT-induced changes in perfusion and diffusion. Quantitative imaging features from mpMRI show promise as being predictive of endpoint biopsy positivity.We investigated the longitudinal changes in multiparametric MRI (mpMRI) , and Dynamic Contrast Enhanced (DCE-)MRI) of prostate cancer patients receiving Lattice Extreme Ablative Dose (LEAD) radiotherapy (RT) and the capability of their imaging features to predict RT outcome based on endpoint biopsies. Ninety-five mpMRI exams from 25 patients, acquired pre-RT and at 3-, 9-, and 24-months post-RT were analyzed. MRI/Ultrasound-fused biopsies were acquired pre- and at two-years post-RT (endpoint). Five regions of interest (ROIs) were analyzed: Gross tumor volume (GTV), normally-appearing tissue (NAT) and peritumoral volume in both peripheral (PZ) and transition (TZ) zones. Diffusion and perfusion radiomics features were extracted from mpMRI and compared before and after RT using two-tailed Student t-tests. Selected features at the four scan points and their differences (Δ radiomics) were used in multivariate logistic regression models to predict the endpoint biopsy positivity. Baseline ADC values were significantly different between GTV, NAT-PZ, and NAT-TZ ( Prostate cancer has a long natural history , and loctrans-forward volume transfer constant and kep-reverse reflux rate constant between extracellular-extravascular space (EES) and plasma. Another estimated parameter is ve, which represents the EES fraction [Diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences in mpMRI provide quantitative measurements related to functional properties of tissues ,18. DWI fraction ,22. In sIn this study of prospectively collected data, we characterize longitudinal changes in tumor, peritumoral, and normally-appearing tissues of the peripheral (NAT-PZ) and transition zones (NAT-TZ) following administration of Lattice Extreme Ablative Dose (LEAD) RT. The LEAD technique, a spatially-fractionated external beam RT (EBRT) conceptualized as a depth extension of GRID RT ,24 is a Prostate cancer patients received the LEAD RT as part of one of the University of Miami investigator-initiated clinical trials: The Miami BLaStM trial  or the LEAD trial . Both trials were approved by the Institutional Review Board at the University of Miami. Written informed consent was obtained from all patients. All biopsies were reviewed by an experienced GU specialist pathologist (ONK) at the University of Miami according to the most contemporary prostate cancer grading recommendations . For diaThe LEAD RT technique was described in detail by Pollack et al. . BrieflympMRI exams were performed pre-RT (baseline) and at 3-, 9-, and 24-months post-RT. All patients in the study received mpMRI with sequences and sequence parameters consistent with the recommendation for PIRADS v2 : T2-weigAt 2–2.5 years after completion of RT treatment, the patients underwent a 12-core template needle biopsy of the prostate, and 2 additional biopsy cores were obtained from any suspicious functional mpMRI areas and/or the original site of biopsy confirmation of prostate cancer at diagnosis. The rationale for the biopsies at 2–2.5 years was to evaluate the extent of disease eradication, as well as the prognostic significance of positive biopsies in men who were otherwise free of evidence of disease .The prostate and prostate peripheral zone (PZ) were manually contoured on the diagnostic (pre-RT) T2W in MIM software . The GTVs were determined based on mpMRI-defined suspicious lesions recognized by early phase contrast enhancement on DCE-MRI or by water restriction on the ADC, along with abnormalities on T2W imaging . When ne2. Using the prostate contours, they were cropped to the prostate region of interest (with 10 pixels (5 mm) padding along the x and y coordinates). Similarly, all volumes were interpolated to 3 mm slice thickness to account for resolution differences during acquisition.For each mpMRI exam , axial TThe contours of the transition zone (TZ) were calculated by subtracting the PZ from the prostate regions. To capture the immediate GTV environment, peritumoral (PT) rings of 5 mm thicknesses were automatically defined (PT-GTV) . The inttrans (min−1), a volume transfer constant of the contrast related to perfusion and permeability per unit volume of tissue; kep (min−1), the transport rate constant of the contrast from the extracellular-extravascular space (EES) to the vascular space; and ve, the EES fraction. In addition, tonset, the time of contrast wash-in; AUC90 and AUC120, the areas under the averaged contrast-to-time curve for the first 90 and 120 s, respectively, were calculated. A summary of the considered ROIs and radiomic features is provided in Eleven first-order statistics were calculated for each ROI on ADC. These features included histogram characteristics such as percentiles, mean, standard deviation, skewness, and kurtosis . For DCEp-value < 0.05) were then ranked based on ascending Welch’s t-test p-value, and the first  feature is selected. An iterative procedure was devised to select an uncorrelated subset of the remaining features by removing features that are highly correlated (Pearson r > 0.85) with an already selected feature. The set of selected features are modeled using a multivariate logistic regression. The AUC for the model is reported as a performance measure and is calculated using the Leave-One-Out method. The model performance was also summarized in the confusion matrix.The ADCs and DCE features at baseline were compared between the GTV, NAT-PZ, and NAT-TZ using two-tailed Student t-tests. The same tests were used to describe the changes longitudinally pre- and post-RT. The features at the four mpMRI scan points (S1–S4) and their differences were investigated for correlation with the endpoint biopsy. Ten comparisons were conducted with the dichotomized outcome variable. For each comparison, the radiomics features were assessed for association with the endpoint biopsy positivity via a univariate logistic regression. Features that are significant  and 4 patients with positive endpoint biopsy from the BlaStM trial. Baseline clinical, pathologic, and other characteristics are reported in trans was significantly lower in NAT-PZ in comparison with the other two volumes. kep was significantly different between GTV and NAT-TZ; kep in NAT-TZ was significantly higher than in other two ROIs.In total, 94 mpMRI examinations from 25 patients, including pre-RT (N = 25), 3 months post-RT (N = 25), 9 months post-RT (N = 24), and 24 months post-RT (N = 20)  were anaep, and ve changed significantly in the GTV at 3 months post-RT in comparison with baseline (ep continued to significantly decrease (p < 0.001) gradually in GTV . The most dramatic change in Ktrans was in the NAT (−69.79% in PZ and +20.80% in TZ). Similarly, to ADC, in all perfusion comparisons, the values in the 3 volumes at 24 months were not statistically different.The longitudinal changes of the diffusion and perfusion imaging features before and after LEAD-RT are shown in baseline  Table A3baseline , there we, PT-PZ_ADC_Mean, and NAT-TZ_DCE_ve . The Receiver Operating Characteristic (ROC) curve for the baseline model and the confusion matrix are shown in 1 Score = 0.80). The confusion matrix indicates that all four patients with positive biopsies were correctly classified. For the three-months post-RT model, the selected features were: NAT-TZ_DCE_AUC120; GTV_DCE_SD, GTV_DCE_Ktrans, and NAT-TZ_ADC_SD. This model also shows high predictive power of endpoint biopsy positivity . The ROC curve for the three-months post-RT model and the confusion matrix is shown in Using the procedure described in the Methods sections, the associations of the imaging features at each of the four scan points  with thetrans, and other features related to vascular perfusion/permeability, could provide useful quantitative, physiological, and functional information about the effects of radiotherapy on prostate cancer patients. To the best of our knowledge, this is the first study to combine quantitative diffusion and perfusion at multiple scan points (pre- and post-RT) to monitor the changes not only in the tumor (GTV) but also in peritumoral and normal tissues. We also built a radiomics-based prediction model for patient outcome using the second year post-RT biopsy as an endpoint.Early biomarkers for RT response are of paramount importance, especially for prostate cancer, which requires years of follow-up to determine treatment failure. In this work, we chose to characterize the longitudinal changes in several quantitative imaging features that are related to the physiological and functional response to therapy. ADC, a marker of tissue water diffusion restriction and cellularity, KThe expression of the features at baseline in GTV and NAT is consistent with the tissue composition of the tumor and normal PZ and TZ. Low ADC values in GTV  reflect trans reflects the uptake of the contrast agent, which is affected by the combined effect of tissue blood flow and permeability. The high Ktrans at baseline in GTV was due to the increased neovascularization, vascular density, and vascular permeability in the tumor [trans due to the predominantly glandular composition of the PZ. The basement membrane lining the benign glands does not allow the contrast to penetrate inside the glands [ep is a parameter that reflects the return of the contrast agent to the blood vessel. The increased neovascularization of the tumor may have higher vascular density per unit area and altered vascular structure that may lead to an increased permeability, making it easier for the contrast to return back to the vascular space, explaining a significantly higher kep in GTV.Khe tumor ,37. NAT-e glands . kep is The observed ADC’s increase in GTV following RT is consistent with the significant reduction of the tumor volume and reduced tumor cellularity, the dispersed individual cell pattern of cancer cell distribution. Conversely, ADC is decreased in NAT-PZ. These findings align well with the fact that RT is known to induce involution of glandular tissue in addition to increased stromal volume on histopathology. In summary, during the early stages after RT, the GTV, NAT-PZ, and NAT-TZ have different dynamics of imaging feature characteristics, but after two years the radiological appearance becomes similar between the three compartments. Such a phenomenon is most likely explained by the natural evolution in cancer and benign tissue of different zones of the prostate that takes place over time after irradiation.2/s and at 6- and 12-month post-RT- 1160 mm2/s and 1520 mm2/s, respectively [2/s to 1300 mm2/s in the tumor during EBRT, where MRI was acquired every two weeks throughout eight weeks of image-guided prostate IMRT (n = 17) [The increase of tumor ADC values after radiation therapy is reported in several studies. Pasquier et al. report median ADC (n = 13) at baseline 1140 mmectively . Foltz etrans in GTV. In Franiel et al., the initial increase in Ktrans in NAT was attributed to the inflammatory reaction of the tissue to radiotherapy [Radiation causes devascularization in both tumorous and benign prostatic tissue . This alotherapy .trans for the patients with positive and negative biopsies. Of a note, mpMRI in these studies was acquired shortly after the post-treatment biopsy. In contrast, our study identified imaging features that potentially can serve as actionable biomarker at early scan points.This study is the first to comprehensively evaluate pre- and post-RT mpMRI associations with a second-year biopsy positivity endpoint. Prostate biopsies taken at 2–3 years after RT are strongly associated with eventual biochemical failure, clinical failure, and survival ,11,42. B2/s was determined with a sensitivity of 100% and a specificity of 48% for predicting biochemical failure. Although the authors caution that the absolute ADC values might vary slightly between scanners and with the choice of imaging parameters, this cutoff point clearly separated the two groups of patients in our study . Interestingly, when DCE features were investigated, Chatterjee et al. did not identify any associations of these features with failure [p < 0.001) with a cut-off value for the post-IMRT ADC value of 1340 mm2/s .Several quantitative imaging features are promising predictors of treatment failure based on post-treatment positive biopsy, a strong marker for clinically relevant endpoints. About a third of the investigated patients in a randomized hypofractionation trial had positive biopsies . In addi failure . Using b failure . In mult failure . SeventyStudying the peritumoral tissue used for investigating imaging changes post-RT is a novel element in our study. Peritumoral regions may encode useful information as prostate cancer influences its surrounding habitat . This adRisk stratification is critical for determining the optimal treatment for patients with localized prostate cancer. mpMRI-derived quantitative features are appealing as imaging biomarkers because the acquisition is noninvasive and does not use ionizing radiation, yet it is quantitative. DWI-derived features are especially attractive as they do not require any exogenous contrast agents and can be obtained relatively rapidly . By deteThere are several limitations to consider for this analysis. The preliminary findings of this pilot study should be validated in a larger prospective cohort. The research was conducted within a single-institution academic setting with subspecialized multidisciplinary expertise and the performance of the created models may not be generalizable to community practice. The performance of the models will most likely deteriorate in larger, more heterogenous dataset. The schema of the clinical trial included 4 mpMRIs exams. MpMRI exams are expensive and often cumbersome for the patients. One of the aims of a future study with a larger cohort is to identify the optimal number and time-point of collection after RT to mpMRI with the goal to reduce the number of mpMRIs.This work aimed at exploring the prognostic value of quantitative mpMRI features as a potential clinical tool to identify which patients would fail curative radiotherapy. As such, many questions for clinical post-radiotherapy management selection are beyond the scope of this work.trans values in both tumorous and benign prostatic tissue [We limited the analysis to perfusion and diffusion sequences of the mpMRI because we were interested in changes with direct physiological interpretation. For the same reason we selected the pharmaco-kinetics parameters for DCE analysis. Future analysis will include also higher order radiomics features, such as textures, etc. The T2 relaxation times were not investigated as the clinical mpMRI protocol  did not c tissue  because c tissue , we did In conclusion, our study demonstrated that RT causes significant changes to quantitative perfusion and diffusion imaging features in both tumorous and normally-appearing prostatic tissue. Because of the noninvasive nature of the mpMRI, acquiring multiple exams post-RT are feasible to monitor treatment response. Several quantitative imaging features are promising predictors of treatment failure based on post-treatment positive biopsy, a strong marker for clinically relevant endpoints. By creating a pipeline for automatic analysis of longitudinal mpMRI datasets, these studies can be expanded to larger patient cohorts for straightening, conformation, and validation of these preliminary results.