bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of conversion to dementia using interpretable machine learning in patients with amnestic mild cognitive impairment
Authors: Chun Min Young , Park Chae Jung , Kim Jonghyuk , Jeong Jee Hyang , Jang Hyemin , Kim Kyunga , Seo Sang Won
Published: August 2022

Purpose

Amnestic mild cognitive impairment (aMCI) is a transitional state between normal aging and Alzheimer’s disease (AD). However, not all aMCI patients are observed to convert to AD dementia. Therefore, developing a predictive algorithm for the conversion of aMCI to AD dementia is important. Parametric methods, such as logistic regression, have been developed; however, it is difficult to reflect complex patterns, such as non-linear relationships and interactions between variables. Therefore, this study aimed to improve the predictive power of aMCI patients’ conversion to dementia by using an interpretable machine learning (IML) algorithm and to identify the factors that increase the risk of individual conversion to dementia in each patient.

Methods

We prospectively recruited 705 patients with aMCI who had been followed-up for at least 3 years after undergoing baseline neuropsychological tests at the Samsung Medical Center between 2007 and 2019. We used neuropsychological tests and apolipoprotein E (APOE) genotype data to develop a predictive algorithm. The model-building and validation datasets were composed of data of 565 and 140 patients, respectively. For global interpretation, four algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) were compared. For local interpretation, individual conditional expectations (ICE) and SHapley Additive exPlanations (SHAP) were used to analyze individual patients.

Results

Among the four algorithms, the extreme gradient boost model showed the best performance, with an area under the receiver operating characteristic curve of 0.852 and an accuracy of 0.807. Variables, such as age, education, the scores of visuospatial and memory domains, the sum of boxes of the Clinical Dementia Rating scale, Mini-Mental State Examination, and APOE genotype were important features for creating the algorithm. Through ICE and SHAP analyses, it was also possible to interpret which variables acted as strong factors for each patient.

Conclusion

We were able to propose a predictive algorithm for each aMCI individual’s conversion to dementia using the IML technique. This algorithm is expected to be useful in clinical practice and the research field, as it can suggest conversion with high accuracy and identify the degree of influence of risk factors for each patient.
Quantitative susceptibility mapping and blood neurofilament light chain differentiate between parkinsonian disorders
Authors: Zhang Piao , Chen Junling , Cai Tongtong , He Chentao , Li Yan , Li Xiaohong , Chen Zhenzhen , Wang Lijuan , Zhang Yuhu
Published: August 2022

Objectives

We employed quantitative susceptibility mapping (QSM) to assess iron deposition in parkinsonian disorders and explored whether combining QSM values and neurofilament light (NfL) chain levels can improve the accuracy of distinguishing Parkinson’s disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).

Materials and methods

Forty-seven patients with PD, 28 patients with MSA, 18 patients with PSP, and 28 healthy controls (HC) were enrolled, and QSM data were reconstructed. Susceptibility values in the bilateral globus pallidus (GP), putamen (PUT), caudate nucleus (CN), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) were obtained. Plasma NfL levels of 47 PD, 18 MSA, and 14 PSP patients and 22 HC were measured by ultrasensitive Simoa technology.

Results

The highest diagnostic accuracy distinguishing MSA from PD patients was observed with increased susceptibility values in CN (AUC: 0.740). The susceptibility values in RN yielded the highest diagnostic performance for distinguishing PSP from PD patients (AUC: 0.829). Plasma NfL levels were significantly higher in the MSA and PSP groups than in PD and HC groups. Combining the susceptibility values in the RN and plasma NfL levels improved the diagnostic performance for PSP vs. PD (AUC: 0.904), whereas plasma NfL levels had higher diagnostic accuracy for MSA vs. PD (AUC: 0.877).

Conclusion

The exploratory study indicates different patterns of iron accumulation in deep gray matter nuclei in Parkinsonian disorders. Combining QSM values with NfL levels may be a promising biomarker for distinguishing PSP from PD, whereas plasma NfL may be a reliable biomarker for differentiating MSA from PD. QSM and NfL measures appeared to have low accuracy for separating PD from controls.
Is liquid biopsy mature enough for the diagnosis of Alzheimer’s disease?
Authors: Gong Xun , Zhang Hantao , Liu Xiaoyan , Liu Yi , Liu Junlin , Fapohunda Funmilayo O. , Lü Peng , Wang Kun , Tang Min
Published: August 2022

The preclinical diagnosis and clinical practice for Alzheimer’s disease (AD) based on liquid biopsy have made great progress in recent years. As liquid biopsy is a fast, low-cost, and easy way to get the phase of AD, continual efforts from intense multidisciplinary studies have been made to move the research tools to routine clinical diagnostics. On one hand, technological breakthroughs have brought new detection methods to the outputs of liquid biopsy to stratify AD cases, resulting in higher accuracy and efficiency of diagnosis. On the other hand, diversiform biofluid biomarkers derived from cerebrospinal fluid (CSF), blood, urine, Saliva, and exosome were screened out and biologically verified. As a result, more detailed knowledge about the molecular pathogenesis of AD was discovered and elucidated. However, to date, how to weigh the reports derived from liquid biopsy for preclinical AD diagnosis is an ongoing question. In this review, we briefly introduce liquid biopsy and the role it plays in research and clinical practice. Then, we summarize the established fluid-based assays of the current state for AD diagnostic such as ELISA, single-molecule array (Simoa), Immunoprecipitation–Mass Spectrometry (IP–MS), liquid chromatography–MS, immunomagnetic reduction (IMR), multimer detection system (MDS). In addition, we give an updated list of fluid biomarkers in the AD research field. Lastly, the current outstanding challenges and the feasibility to use a stand-alone biomarker in the joint diagnostic strategy are discussed.
The role of motivation factors in exergame interventions for fall prevention in older adults: A systematic review and meta-analysis
Authors: Buyle Margot , Jung Yujin , Pavlou Marousa , Gonzalez Sergi Costafreda , Bamiou Doris-Eva
Published: August 2022

Balance disorders and falls are common in the elderly population. Regular balance exercises are an evidence-based physical intervention to prevent falls in older adults, while patient motivation and adherence are important factors for intervention outcome. Exergames are a relatively new, alternative intervention for physical rehabilitation as they improve balance and strength in older adults. The aims of this systematic review and meta-analysis were to assess the (1) effect of motivation factors as per the Capability, Opportunity and Motivation model of Behavior change (COM-B) on the effectiveness of exergame interventions in healthy older adults, (2) effectiveness of exergames to improve balance in older healthy adults and, (3) impact of exergames on cognitive outcomes. Results show that motivation and capability components influence the general outcome of the exergame training. Motivational factors should thus be considered when setting-up an exergame intervention. Furthermore, exergame intervention appears to be a promising training method in comparison to traditional exercise training. However, exergame training in itself might not be sufficient to improve fall risk and cognitive performance.
Intraneural or extraneural ganglion cysts as a cause of cubital tunnel syndrome: A retrospective observational study
Authors: Yalikun Ainizier , Yushan Maimaiaili , Hamiti Yimurang , Lu Cheng , Yusufu Aihemaitijiang
Published: August 2022

Purpose

Cubital tunnel syndrome caused by ganglion cysts has rarely been reported. The purpose of this study was to evaluate the surgical treatment outcomes of a patient diagnosed with cubital tunnel syndrome caused by intraneural or extraneural cysts and to summarize our experience.

Method

In total, 34 patients were evaluated retrospectively from January 2011 to January 2020 with a follow-up of more than 24 months. Preoperative data, such as demographic data, clinical symptoms, physical examination findings, and laboratory tests, were all recorded and pre-operative and post-operative data were compared. The function was evaluated by the modified Bishop scoring system and the McGowan grade at the last follow-up.

Results

Improvement of interosseous muscle strength, the Visual Analog Scale (VAS), 2-point discrimination (2-PD), electromyogram (EMG) result, Wartenberg sign, claw hand, and weakness could be clearly observed in all patients. Extraneural cysts were completely removed and the pedicles of the cysts were ligated. Intraneural cysts were incised and drained, and part of their cyst walls were removed using a microsurgical technique. All patients underwent anterior subcutaneous transposition (AST). At the last follow-up, McGowan's (0-IIa) grade increased from seven patients (20.6%) preoperatively to 27 patients (79.4%); the excellent and good rate according to the modified Bishop scoring system was 82.4% (28 patients), and all patients had no symptoms of recurrence after surgery.

Conclusion

The treatment of cubital tunnel syndrome caused by intraneural or extraneural cysts achieved good long-term results through extraneural cyst resection or intraneural cyst incision and drainage combined with subcutaneous transposition. Early diagnosis and surgical treatment are essential for the patient's postoperative recovery.
The impact of cathodal tDCS on the GABAergic system in the epileptogenic zone: A multimodal imaging study
Authors: Abuhaiba Sulaiman I. , Duarte Isabel C. , Castelhano João , Dionísio Ana , Sales Francisco , Edden Richard , Castelo-Branco Miguel
Published: August 2022

Objectives

We aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epileptiform interictal discharges (IEDs) and to measure brain metabolites in the epileptogenic zone (EZ) and control regions simultaneously in patients with pharmacoresistant epilepsy.

Methods

This is a hypothesis-driven pilot prospective single-blinded repeated measure design study in patients diagnosed with pharmacoresistant epilepsy of temporal lobe onset. We included seven patients who underwent two sessions of c-tDCS (sham followed by real). The real tDCS session was 20 min in duration and had a current intensity of 1.5 mA delivered via two surface electrodes that had dimensions of 3 × 4 cm. The cathode electrode was placed at FT7 in the center whereas the anode at Oz in the center. After each session, we performed electroencephalographic recording to count epileptiform IEDs over 30 min. We also performed magnetic resonance spectroscopy (MRS) to measure brain metabolite concentrations in the two areas of interest (EZ and occipital region), namely, gamma-aminobutyric acid (GABA), glutamate (Glx), and glutathione. We focused on a homogenous sample where the EZ and antiepileptic medications are shared among patients.

Results

Real tDCS decreased the number of epileptiform IEDs per min (from 9.46 ± 2.68 after sham tDCS to 5.37 ± 3.38 after real tDCS), p = 0.018, as compared to sham tDCS. GABA was decreased in the EZ after real c-tDCS stimulation as compared to sham tDCS (from 0.129 ± 0.019 to 0.096 ± 0.018, p = 0.02). The reduction in EZ GABA correlated with the reduction in the frequency of epileptiform IED per min (rho: 0.9, p = 0.003).

Conclusion

These results provide a window into the antiepileptic mechanisms of action of tDCS, based on local and remote changes in GABA and neural oscillatory patterning responsible for the generation of interictal epileptiform discharges.
Early depression screening and short-term functional outcome in hospitalized patients for acute ischemic stroke
Authors: Baik Minyoul , Lee Hyungwoo , Lee Il Hyung , Heo JoonNyung , Nam Hyo Suk , Lee Hye Sun , Kim Young Dae
Published: August 2022

Background

Patients with ischemic stroke are at high risk for post-stroke depression (PSD). There are limited data regarding the clinical impact of early PSD, assessed in hospitalized patients with acute ischemic stroke.

Methods

This hospital-based observational cohort study included consecutive patients with acute ischemic stroke or transient ischemic attack between July 2019 and June 2021. In the study hospital, all admitted patients were systematically screened for depression. The depression was screened using the Patient Health Questionnaire-9 (PHQ-9), and PHQ-9 positivity indicated early PSD, which was defined as a score of >4. Logistic regression analyses were used to compare the rates of poor functional outcomes at 3 months in patients with and without PHQ-9 positivity.

Results

Among 1339 patients admitted during the study period, 775 were included, with a median age of 68.0 years, and 316 (40.8%) were women. A total of 111 (14.3%) patients were PHQ-9 positive. History of cancer and early neurological deterioration were independently associated with PHQ-9 positivity. Poor functional outcomes at 3 months were observed in 147 patients (18.8%). PHQ-9 positivity independently showed a 2.2-fold increased risk of poor functional outcome at 3 months (Odds ratio 2.23; 95% confidence interval 1.05–4.73, P = 0.037).

Conclusions

Patients with history of cancer and early neurological deterioration were at risk for early PSD. Early PSD was independently associated with poor functional outcomes at 3 months. The identification of early depression could offer opportunities for further questioning and exploration of symptoms, as well as interventions.
Effectiveness and safety of EVT in patients with acute LVO and low NIHSS
Authors: Kim Beom Joon , Menon Bijoy K. , Yoo Joonsang , Han Jung Hoon , Kim Bum Joon , Kim Chi Kyung , Kim Jae Guk , Kim Joon-Tae , Park Hyungjong , Baik Sung Hyun , Han Moon-Ku , Kang Jihoon , Kim Jun Yup , Lee Keon-Joo , Park Jong-Moo , Kang Kyusik , Lee Soo Joo , Cha Jae-Kwan , Kim Dae-Hyun , Jeong Jin-Heon , Park Tai Hwan , Park Sang-Soon , Lee Kyung Bok , Lee Jun , Hong Keun-Sik , Cho Yong-Jin , Park Hong-Kyun , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi-Sun , Kim Dong-Eog , Ryu Wi-Sun , Choi Kang-Ho , Choi Jay Chol , Kim Joong-Goo , Kwon Jee-Hyun , Kim Wook-Joo , Shin Dong-Ick , Yum Kyu Sun , Sohn Sung-Il , Hong Jeong-Ho , Kim Chulho , Lee Sang-Hwa , Lee Juneyoung , Almekhlafi Mohammed A. , Demchuk Andrew , Bae Hee-Joon
Published: August 2022

Background and purpose

There is much uncertainty in endovascular treatment (EVT) decisions in patients with acute large vessel occlusion (LVO) and mild neurological deficits.

Methods

From a prospective, nationwide stroke registry, all patients with LVO and baseline NIHSS <6 presenting within 24 h from the time last known well (LKW) were included. Early neurological deterioration (END) developed before EVT was prospectively collected as an increasing total NIHSS score ≥2 or any worsening of the NIHSS consciousness or motor subscores during hospitalization not related to EVT. Significant hemorrhage was defined as PH2 hemorrhagic transformation or hemorrhage at a remote site. The modified Rankin Scale (mRS) was prospectively collected at 3 months.

Results

Among 1,083 patients, 149 (14%) patients received EVT after a median of 5.9 [3.6–12.3] h after LKW. In propensity score-matched analyses, EVT was not associated with mRS 0-1 (matched OR 0.99 [0.63–1.54]) but increased the risk of a significant hemorrhage (matched OR, 4.51 [1.59–12.80]). Extraneous END occurred in 207 (19%) patients after a median of 24.5 h [IQR, 13.5–41.9 h] after LKW (incidence rate, 1.41 [95% CI, 1.23–1.62] per 100 person-hours). END unrelated to EVT showed a tendency to modify the effectiveness of EVT (P-for-interaction, 0.08), which decreased the odds of having mRS 0–1 in mild LVO patients without END (adjusted OR, 0.63 [0.40–0.99]).

Conclusions

The use of EVT in patients with acute LVO and low NIHSS scores may require the assessment of individual risks of early deterioration, hemorrhagic complications and expected benefit.
What names for covert awareness? A systematic review
Authors: Schnakers Caroline , Bauer Chase , Formisano Rita , Noé Enrique , Llorens Roberto , Lejeune Nicolas , Farisco Michele , Teixeira Liliana , Morrissey Ann-Marie , De Marco Sabrina , Veeramuthu Vigneswaran , Ilina Kseniya , Edlow Brian L. , Gosseries Olivia , Zandalasini Matteo , De Bellis Francesco , Thibaut Aurore , Estraneo Anna
Published: August 2022

Background

With the emergence of Brain Computer Interfaces (BCI), clinicians have been facing a new group of patients with severe acquired brain injury who are unable to show any behavioral sign of consciousness but respond to active neuroimaging or electrophysiological paradigms. However, even though well documented, there is still no consensus regarding the nomenclature for this clinical entity.

Objectives

This systematic review aims to 1) identify the terms used to indicate the presence of this entity through the years, and 2) promote an informed discussion regarding the rationale for these names and the best candidates to name this fascinating disorder.

Methods

The Disorders of Consciousness Special Interest Group (DoC SIG) of the International Brain Injury Association (IBIA) launched a search on Pubmed and Google scholar following PRISMA guidelines to collect peer-reviewed articles and reviews on human adults (>18 years) published in English between 2006 and 2021.

Results

The search launched in January 2021 identified 4,089 potentially relevant titles. After screening, 1,126 abstracts were found relevant. Finally, 161 manuscripts were included in our analyses. Only 58% of the manuscripts used a specific name to discuss this clinical entity, among which 32% used several names interchangeably throughout the text. We found 25 different names given to this entity. The five following names were the ones the most frequently used: covert awareness, cognitive motor dissociation, functional locked-in, non-behavioral MCS (MCS*) and higher-order cortex motor dissociation.

Conclusion

Since 2006, there has been no agreement regarding the taxonomy to use for unresponsive patients who are able to respond to active neuroimaging or electrophysiological paradigms. Developing a standard taxonomy is an important goal for future research studies and clinical translation. We recommend a Delphi study in order to build such a consensus.
Brain alterations of regional homogeneity, degree centrality, and functional connectivity in vulnerable carotid plaque patients with neither clinical symptoms nor routine MRI lesions: A resting-state fMRI study
Authors: Wang Qian , Xing Wu , Ouyang Lirong , Li Lang , Jin Hong , Yang Shuai
Published: August 2022

Aims

Based on resting-state functional MRI (fMRI), we preliminarily explored brain alterations in asymptomatic patients with vulnerable carotid plaques, but carotid stenosis was < 50%.

Methods

A total of 58 asymptomatic patients with vulnerable carotid plaques (stenosis <50%) and 38 healthy controls were recruited. Between-group differences in regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were analyzed. Correlation analysis was performed between the ReHo or DC values in altered brain regions as well as voxel-wise abnormal FC and scores on neuropsychiatric scales, serum interleukin-6 (IL-6), and C-reactive protein (CRP).

Results

Both ReHo and DC values on the left superior occipital gyrus (SOG.L) of the asymptomatic vulnerable carotid plaque group reduced, regardless of plaque location (left, right, or bilateral). Functional connections weakened between the SOG.L and right lingual gyrus (LING.R)/right inferior occipital gyrus (IOG.R), right middle frontal gyrus (MFG.R)/orbital part of superior frontal gyrus (ORBsup.R)/orbital part of middle frontal gyrus (ORBmid.R), left precentral gyrus (PreCG.L)/postcentral gyrus (PoCG.L), left supplementary motor area (SMA.L), right paracentral lobule (PCL.R), left precuneus (PCUN.L), and right postcentral gyrus (PoCG.R)/PCL.R. In ReHo-altered brain regions, ReHo values were positively correlated with Hamilton Rating Scale for Depression (HAMD) scores, and the setting region of abnormal ReHo as seed points, voxel-wise FC between the SOG.L and PreCG.L was negatively correlated with CRP.

Conclusions

Cerebral alterations of neuronal synchronization, activity, and connectivity properties in the asymptomatic vulnerable carotid plaque group were independent of the laterality of vulnerable carotid plaques. Significant relation between ReHo values on the SOG.L and HAMD indicated that even when there were neither clinical symptoms nor lesions on routine MRI, brain function might have changed already at an early stage of carotid atherosclerosis. Inflammation might play a role in linking vulnerable carotid plaques and changes of resting-state functional connectivity.
Regulation of cocaine seeking behavior by locus coeruleus noradrenergic activity in the ventral tegmental area is time- and contingency-dependent
Authors: Solecki Wojciech B. , Kielbinski Michał , Wilczkowski Michał , Zajda Katarzyna , Karwowska Karolina , Joanna Bernacka , Rajfur Zenon , Przewłocki Ryszard
Published: August 2022

Substance use disorder is linked to impairments in the ventral tegmental area (VTA) dopamine (DA) reward system. Noradrenergic (NA) inputs from locus coeruleus (LC) into VTA have been shown to modulate VTA neuronal activity, and are implicated in psychostimulant effects. Phasic LC activity controls time- and context-sensitive processes: decision making, cognitive flexibility, motivation and attention. However, it is not yet known how such temporally-distinct LC activity contributes to cocaine seeking. In a previous study we demonstrated that pharmacological inhibition of NA signaling in VTA specifically attenuates cocaine-seeking. Here, we used virally-delivered opsins to target LC neurons for inhibition or excitation, delivered onto afferents in VTA of male rats seeking cocaine under extinction conditions. Optogenetic stimulation or inhibition was delivered in distinct conditions: upon active lever press, contingently with discreet cues; or non-contingently, i.e., throughout the cocaine seeking session. Non-contingent inhibition of LC noradrenergic terminals in VTA attenuated cocaine seeking under extinction conditions. In contrast, contingent inhibition increased, while contingent stimulation reduced cocaine seeking. These findings were specific for cocaine, but not natural reward (food) seeking. Our results show that NA release in VTA drives behavior depending on timing and contingency between stimuli – context, discreet conditioned cues and reinforcer availability. We show that, depending on those factors, noradrenergic signaling in VTA has opposing roles, either driving CS-induced drug seeking, or contributing to behavioral flexibility and thus extinction.
A spatio-temporal learning-based model for sleep apnea detection using single-lead ECG signals
Authors: Chen Junyang , Shen Mengqi , Ma Wenjun , Zheng Weiping
Published: August 2022

Sleep apnea (SA) is a common chronic sleep breathing disorder, which would cause stroke, cognitive decline, cardiovascular disease, or even death. The SA symptoms often manifest as frequent breathing interruptions during sleep and most individuals with sleeping disorders are not aware of the SA events. Using a portable device with single-lead ECG signal is an effective way to help an individual to monitor their sleep conditions at home. However, the SA detection performance of ECG-based methods is still difficult to meet the clinical practice requirement. In this study, we propose an end-to-end spatio-temporal learning-based SA detection method, which consists of multiple spatio-temporal blocks. Each block has the identical architecture with a convolutional neural network (CNN) layer, a max-pooling layer, and a bi-gated recurrent unit (BiGRU) layer. This architecture with repeated spatio-temporal blocks can well capture the morphological spatial feature information as well as the temporal feature information from ECG signals. The proposed SA detection model was evaluated on the publicly available datasets of PhysioNet Apnea-ECG dataset (Apnea-ECG) and University College Dublin Sleep Apnea Database (UCDDB). Extensive experimental results show that our proposed SA model on both Apnea-ECG and UCDDB datasets achieves state-of-the-art results, which are obviously superior to existing ECG-based SA detection methods. It means that our proposed method has the potential to be deployed into a healthcare system to provide a sleep monitoring service, which can screen out SA population with high risk and help to take timely interventions to prevent serious consequences.
A diagnostic index based on pseudo-continuous arterial spin labeling and T1-mapping improves efficacy in discriminating Alzheimer’s disease from normal cognition
Authors: Wang Xiaonan , Wang Di , Li Xinyang , Wang Wenqi , Gao Ping , Lou Baohui , Pfeuffer Josef , Zhang Xianchang , Zhu Jinxia , Li Chunmei , Chen Min
Published: August 2022

Background

Pseudo-continuous arterial spin labeling (pCASL) is widely used to quantify cerebral blood flow (CBF) abnormalities in patients with Alzheimer’s disease (AD). T1-mapping techniques assess microstructural characteristics in various pathologic changes, but their application in AD remains in the exploratory stage. We hypothesized that combining quantitative CBF and T1 values would generate diagnostic results with higher accuracy than using either method alone in discriminating AD patients from cognitively normal control (NC) subjects.

Materials and methods

A total of 45 patients diagnosed with AD and 33 NC subjects were enrolled, and cognitive assessment was performed for each participant according to the Chinese version of the Mini-Mental State Examination (MMSE). T1-weighted magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) and pCASL sequence were scanned on a 3T MR scanner. A brain morphometric analysis was integrated into prototype sequence, providing tissue classification and morphometric segmentation results. Quantitative CBF and T1 values of each brain region were automatically generated inline after data acquisition. Independent samples t-test was used to compare regional CBF and T1 values controlled by false discovery rate correction (corrected p < 0.01). The model with combined CBF and T1 values was compared with the individual index by performing receiver operating characteristic curves analysis. The associations between the MMSE score and CBF and T1 values of the brain were investigated using partial correlations.

Results

Cerebral blood flow of the right caudate nucleus (RCc) and left hippocampus (LHc) was significantly lower in the AD group compared with the NC group, while the T1 values of the right caudate nucleus (RCt) and left hippocampus (LHt) increased in the AD group. Prediction accuracies of 73.1, 77.2, 75.9, and 81.3% were achieved for each of the above parameters, respectively. In distinguishing patients from controls using the corresponding optimized cut-off values, most combinations of parameters were elevated (area under curve = 0.775–0.894). The highest area under curve value was 0.944, by combining RCc, LHc, RCt, and LHt.

Conclusion

In this preliminary study, the combined model based on pCASL and T1-mapping improved the diagnostic performance of discriminating AD and NC groups. T1-mapping may become a competitive technique for quantitatively measuring pathologic changes in the brain.
High-frequency repetitive transcranial magnetic stimulation improves spatial episodic learning and memory performance by regulating brain plasticity in healthy rats
Authors: Wu Qi , Xu Xingjun , Zhai Chenyuan , Zhao Zhiyong , Dai Wenjun , Wang Tong , Shen Ying
Published: August 2022

Background

Repetitive transcranial magnetic stimulation (rTMS) is an effective way to stimulate changes in structural and functional plasticity, which is a part of learning and memory. However, to our knowledge, rTMS-induced specific activity and neural plasticity in different brain regions that affect cognition are not fully understood; nor are its mechanisms. Therefore, we aimed to investigate rTMS-induced cognition-related neural plasticity changes and their mechanisms in different brain regions.

Methods

A total of 30 healthy adult rats were randomly divided into the control group and the rTMS group (n = 15 rats per group). The rats in the control and the rTMS group received either 4 weeks of sham or high-frequency rTMS (HF-rTMS) over the prefrontal cortex (PFC). Cognitive function was detected by Morris water maze. Functional imaging was acquired by resting-state functional magnetic resonance imaging (rs-fMRI) before and after rTMS. The protein expressions of BDNF, TrkB, p-Akt, Akt, NR1, NR2A, and NR2B in the PFC, hippocampus, and primary motor cortex (M1) were detected by Western blot following rTMS.

Results

After 4 weeks of rTMS, the cognitive ability of healthy rats who underwent rTMS showed a small but significant behavioral improvement in spatial episodic learning and memory performance. Compared with the pre-rTMS or the control group, rats in the rTMS group showed increased regional homogeneity (ReHo) in multiple brain regions in the interoceptive/default mode network (DMN) and cortico-striatal-thalamic network, specifically the bilateral PFC, bilateral hippocampus, and the left M1. Western blot analyses showed that rTMS led to a significant increase in the expressions of N-methyl-D-aspartic acid (NMDA) receptors, including NR1, NR2A, and NR2B in the PFC, hippocampus, and M1, as well as an upregulation of BDNF, TrkB, and p-Akt in these three brain regions. In addition, the expression of NR1 in these three brain regions correlated with rTMS-induced cognitive improvement.

Conclusion

Overall, these data suggested that HF-rTMS can enhance cognitive performance through modulation of NMDA receptor-dependent brain plasticity.
Comparison of 3DCRT and IMRT out-of-field doses in pediatric patients using Monte Carlo simulations with treatment planning system calculations and measurements
Authors: Sá Ana Cravo , Barateiro Andreia , Bednarz Bryan P. , Almeida Pedro , Vaz Pedro , Madaleno Tiago
Published: August 2022

3DCRT and IMRT out-of-field doses in pediatric patients were compared using Monte Carlo simulations with treatment planning system calculations and measurements.

Purpose

Out-of-field doses are given to healthy tissues, which may allow the development of second tumors. The use of IMRT in pediatric patients has been discussed, as it leads to a “bath” of low doses to large volumes of out-of-field organs and tissues. This study aims to compare out-of-field doses in pediatric patients comparing IMRT and 3DCRT techniques using measurements, Monte Carlo (MC) simulations, and treatment planning system (TPS) calculations.

Materials and methods

A total dose of 54 Gy was prescribed to a PTV in the brain of a pediatric anthropomorphic phantom, for both techniques. To assess the out-of-field organ doses for both techniques, two treatment plans were performed with the 3DCRT and IMRT techniques in TPS. Measurements were carried out in a LINAC using a pediatric anthropomorphic phantom and thermoluminescent dosimeters to recreate the treatment plans, previously performed in the TPS. A computational model of a LINAC, the associated multileaf collimators, and a voxelized pediatric phantom implemented in the Monte Carlo N-Particle 6.1 computer program were also used to perform MC simulations of the out-of-field organ doses, for both techniques.

Results

The results obtained by measurements and MC simulations indicate a significant increase in dose using the IMRT technique when compared to the 3DCRT technique. More specifically, measurements show higher doses with IMRT, namely, in right eye (13,041 vs. 593 mGy), left eye (6,525 vs. 475 mGy), thyroid (79 vs. 70 mGy), right lung (37 vs. 28 mGy), left lung (27 vs. 20 mGy), and heart (31 vs. 25 mGy). The obtained results indicate that out-of-field doses can be seriously underestimated by TPS.

Discussion

This study presents, for the first time, out-of-field dose measurements in a realistic scenario and calculations for IMRT, centered on a voxelized pediatric phantom and an MC model of a medical LINAC, including MLC with log file-based simulations. The results pinpoint significant discrepancies in out-of-field doses for the two techniques and are a cause of concern because TPS calculations cannot accurately predict such doses. The obtained doses may presumably increase the risk of development of second tumors.
Allogeneic Hematopoietic Stem Cell Transplantation for Mixed or Overlap Myelodysplastic/Myeloproliferative Disorders
Authors: Symeonidis Argiris , Chondropoulos Spiros , Verigou Evgenia , Lazaris Vasileios , Kourakli Alexandra , Tsirigotis Panagiotis
Published: August 2022

Chronic myelomonocytic leukemia (CMML) and the remaining, less frequent hybrid, mixed, or overlap myelodysplastic syndromes/myeloproliferative neoplasms (MDSs/MPNs) are difficult to treat neoplastic hematological disorders, exhibiting substantial clinical and prognostic heterogeneity, for which clear therapeutic guidelines or effective treatment options are still missing. CMML has an overall survival ranging from a few months to several years. Although patients with proliferative or dysplastic features may benefit from hydroxyurea and hypomethylating agent treatment, respectively, none of these treatments can establish long-term remission and prevent the inevitable transformation to acute leukemia. Novel targeted treatment approaches are emerging but are still under investigation. Therefore, currently, allogeneic stem cell transplantation (allo-SCT) remains the only treatment modality with a curative potential, but its widespread application is limited, due to significant morbidity and mortality associated with the procedure, especially in the elderly and in patients with comorbidities. Recognition of patient eligibility for allo-SCT is crucial, and the procedure should be addressed to patients with a good performance status without severe comorbidities and mainly to those in intermediate- to high-risk category, with a suitable stem cell donor available. The issues of best timing for performing transplantation, patient and donor eligibility, the type of conditioning regimen, and the outcomes after various allo-SCT procedures are the topics of this review.
Neoadjuvant chemoradiotherapy for resectable gastric cancer: A meta-analysis
Authors: Chen Jiuzhou , Guo Yaru , Fang Miao , Yuan Yan , Zhu Youqi , Xin Yong , Zhang Longzhen
Published: August 2022

Objectives

To evaluate the clinical curative effects and toxicity of neoadjuvant chemoradiotherapy for resectable gastric cancer compared to those of neoadjuvant chemotherapy.

Methods

A systematic review and meta-analysis of the randomized controlled trials (RCTs) of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy were performed in patients with resectable gastric cancer.

Results

Seven RCTs were included (601 patients; 302 in the neoadjuvant chemoradiotherapy group and 299 in the neoadjuvant chemotherapy group). The neoadjuvant chemoradiotherapy group had an increased number of patients with a complete response [odds ratio (OR) = 3.79, 95% confidence interval (CI): 1.68–8.54, p = 0.001] and improved objective response rate (OR = 2.78, 95% CI: 1.69–4.57, p < 0.0001), 1-year (OR = 3.51, 95% CI: 1.40–8.81, p = 0.007) and 3-year (OR = 2.14, 95% CI: 1.30–3.50, p = 0.003) survival rates, R0 resection rate (OR = 2.21, 95% CI: 1.39–3.50, p = 0.0008), and complete pathologic response (OR = 4.39, 95% CI: 1.59–12.14, p = 0.004). Regarding the incidence of adverse effects after neoadjuvant therapy, only the occurrence rate of gastrointestinal reaction in the neoadjuvant chemoradiotherapy group was higher than that in the neoadjuvant chemotherapy group (OR = 1.76, 95% CI: 1.09–2.85, p = 0.02), and there was no significant difference in other adverse effects. There was no difference in the incidence of postoperative complications between the two groups.

Conclusion

Neoadjuvant chemoradiotherapy for resectable gastric cancer has several advantages in terms of efficacy and safety compared to neoadjuvant chemotherapy. Therefore, neoadjuvant chemoradiotherapy has great potential as an effective therapy for resectable gastric cancers.

Systematic Review Registration

https://inplasy.com/inplasy-2022-3-0164, registration number INPLASY202230164.
Safety, tolerability, and pharmacokinetics/pharmacodynamics of JMT103 in patients with bone metastases from solid tumors
Authors: Liang Xu , Xue Junli , Ge Xiaoxiao , Li Jin , Li Huiping , Xue Liqiong , Di Lijun , Tang Wenbo , Song Guohong , Li Qun , Jiang Hanfang , Zhao Wei , Lin Fengjuan , Shao Bin , Yang Xiugao , Wu Zhufeng , Zhang Tianyi , Wang Chenchen , Guo Ye
Published: August 2022

Bone metastases are common complications of solid tumors. The outcome is poor despite major progress in cancer therapies. We describe a multicenter, open-label, phase 1, dose escalation and expansion trial of JMT103, a novel fully humanized receptor activator of nuclear factor kappa-B ligand (RANKL)-targeting monoclonal antibody, in adults with bone metastases from solid tumors. The study assessed the safety, tolerability, and pharmacokinetics/pharmacodynamics of JMT103. Patients received JMT103 at doses of 0.5, 1.0, 2.0, and 3.0 mg/kg every 4 weeks for 3 cycles. Among 59 patients enrolled, 20 and 39 patients participated in the dose-escalation and dose-expansion phases, respectively. One dose-limiting toxicity was observed at 2.0 mg/kg. The maximum tolerated dose was not determined. Treatment-related adverse events were reported in 29 (49.2%) patients, most commonly hypophosphatemia (30.5%), hypocalcemia (23.7%), and hypermagnesemia (10.2%). No treatment-related serious adverse events were reported. Two patients died due to disease progression, which were attributed to gastric cancer and lung neoplasm malignant respectively. Dose proportionality occurred between exposure levels and administered dose was within a dose range of 0.5 to 3.0 mg/kg. The suppression of urinary N-telopeptide corrected for creatinine was rapid, significant, and sustained across all doses of JMT103, with the median change from baseline ranging from –61.4% to –92.2% at day 141. JMT103 was well tolerated in patients with bone metastases from solid tumors, with a manageable safety profile. Bone antiresorptive activity shows the potential of JMT103 for treatment of bone metastases from solid tumors.

Registration No.: NCT03550508; URL: https://www.clinicaltrials.gov/
Comparison of various surgical incisions in parotidectomy: A systematic review and network meta-analysis
Authors: Yin Siyue , Han Yanxun , Liu Yuchen , Chen Bangjie , Fu Ziyue , Sheng Shuyan , Wang Jianpeng , Shen Chuanlu , Wang Xinyi , Jia Yiwen
Published: August 2022

Background

This network meta-analysis aimed to comprehensively compare the operative and postoperative outcomes of different parotidectomy incisions.

Methods

Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials were searched up to April 2022. A complete Bayesian network meta-analysis was performed using the Markov Monte Carlo method in OpenBUGS.

Results

Seventeen studies with 1609 patients were included. Thirteen were retrospective cohort studies, three were prospective cohort studies, and one was a randomized controlled study. The quality of evidence was rated as very low in most comparisons. The incision satisfaction score of the modified facelift incision (MFI), retroauricular hairline incision (RAHI), V-shaped incision (VI) were higher than that of the modified Blair incision (MBI) (MBI vs. MFI: mean difference [MD] -1.39; 95% credible interval [CrI] -2.23, -0.57) (MBI vs. RAHI: MD -2.25; 95% CrI -3.40, -1.12) (MBI vs. VI: MD -2.58; 95% CrI -3.71, -1.46); the tumor size treated by VI was smaller than that by MBI (MD 5.15; 95% CrI 0.76, 9.38) and MFI (MD 5.16; 95% CrI 0.34, 9.86); and the risk of transient facial palsy in the MFI was lower than that in the MBI (OR 2.13; 95% CrI 1.28, 3.64). There were no differences in operation time, drainage volume, wound infection, hematoma, salivary complications, Frey syndrome, or permanent facial palsy between incision types.

Conclusion

The traditional MBI is frequently used for large tumor volumes, but the incision satisfaction score is low and postoperative complication control is poor. However, emerging incisions performed well in terms of incision satisfaction scores and control of complications. More randomized controlled trials are needed to compare the different parotidectomy incisions. Patients should be fully informed about the characteristics of each incision to make the most informed decision, along with the physician’s advice.

Systematic Review Registration

PROSPERO, identifier CRD42022331756
Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity
Authors: Hampton Griffin S. , Bartlette Kai , Nadeau Kristen J. , Cree-Green Melanie , Diniz Behn Cecilia
Published: August 2022

Under healthy conditions, the pancreas responds to a glucose challenge by releasing insulin. Insulin suppresses lipolysis in adipose tissue, thereby decreasing plasma glycerol concentration, and it regulates plasma glucose concentration through action in muscle and liver. Insulin resistance (IR) occurs when more insulin is required to achieve the same effects, and IR may be tissue-specific. IR emerges during puberty as a result of high concentrations of growth hormone and is worsened by youth-onset obesity. Adipose, liver, and muscle tissue exhibit distinct dose-dependent responses to insulin in multi-phase hyperinsulinemic-euglycemic (HE) clamps, but the HE clamp protocol does not address potential differences in the dynamics of tissue-specific insulin responses. Changes to the dynamics of insulin responses would alter glycemic control in response to a glucose challenge. To investigate the dynamics of insulin acting on adipose tissue, we developed a novel differential-equations based model that describes the coupled dynamics of glycerol concentrations and insulin action during an oral glucose tolerance test in female adolescents with obesity and IR. We compared these dynamics to the dynamics of insulin acting on muscle and liver as assessed with the oral minimal model applied to glucose and insulin data collected under the same protocol. We found that the action of insulin on glycerol peaks approximately 67 min earlier (p < 0.001) and follows the dynamics of plasma insulin more closely compared to insulin action on glucose as assessed by the parameters representing the time constants for insulin action on glucose and glycerol (p < 0.001). These findings suggest that the dynamics of insulin action show tissue-specific differences in our IR adolescent population, with adipose tissue responding to insulin more quickly compared to muscle and liver. Improved understanding of the tissue-specific dynamics of insulin action may provide novel insights into the progression of metabolic disease in patient populations with diverse metabolic phenotypes.
The native aortic valve reduces paravalvular leak in TAVR patients
Authors: Prisco Anthony R. , Zhingre-Sanchez Jorge , Mattison Lars , Yannopoulos Demetris , Raveendran Ganesh , Iaizzo Paul A. , Gurevich Sergey
Published: August 2022

Background: Paravalvular leak (PVL) is a frequent TAVR complication. Prospective identification of patients who are likely to develop PVL after TAVR would likely lead to improved outcomes. Prior studies have used geometric characteristics to predict the likelihood of PVL development, but prediction and quantification has not been done. One of the reasons is that it is difficult to predict the mechanical deformation of the native diseased aortic valve prior to implantation of the prosthetic valve, as existing calcifications likely contribute to the seal between the prosthetic valve and the aortic annulus. However, the relatively amount the native valve plays in preventing PVL is unknown.

Methods: A retrospective chart review was conducted identifying patients with mild or greater PVL. One patient who had substantial PVL was identified and a 3D printed (pre-TAVR) aortic root was created. Balloon-expandable TAVR stent frames were implanted within the 3D printed root and a new model was created. Using this geometry, computational fluid dynamics (CFD) simulations were done to quantify PVL. The PVL flow path was iteratively decreased to simulate the space occupied by a crushed native aortic valve and PVL was quantified.

Results: PVL was found to decrease as the space occupying the PVL area increased, demonstrating that the native aortic valve contributes to reducing regurgitation. CFD simulations demonstrated that within the patient analyzed, the native valve occupies between 3–40% of the PVL pathway.

Conclusion:A priori techniques that predict the development of post TAVR PVL should account for the native diseased valve as our simulations demonstrate that it plays a role in reducing PVL.
Association of self-reported snoring with decreased retinal thickness and vessel density
Authors: Xiao Yunfan , Shi Keai , Li Chunmei , Yang Kai , Zhu Xiaoxuan , Su Binbin , Ju Ying , Lu Fan , Qu Jia , Li Ming , Cui Lele
Published: August 2022

Purpose: Self-reported snoring has been reported to influence nerves and vessels. However, there are few direct evidences of snoring related to nerves and microvessels defects. Therefore, we evaluated the association of self-reported snoring with retinal structure and microcirculation.

Methods: A total of 2,622 participants were recruited from the Jidong eye cohort study (JECS). Physical examinations, laboratory tests, and questionnaires were recorded. We also used optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to assess the retinal structure and microvascular network. Snoring was defined as “never,” “occasionally,” and “frequently or more severe” according to self-reported frequency.

Results: The prevalence of snoring were 84.6% (n = 983) and 45.0% (n = 657) in males and females, respectively. Compared with never snoring group, the retinal thickness increased in “occasionally” (p < 0.001) and “frequently or more severe” groups (p = 0.001), while no difference was found between snoring groups (p = 0.14). Superficial retinal capillary plexus (RCP) vessel density was lower in “frequently or more severe” group than in “never” (p < 0.001) and “occasionally” snoring groups (p < 0.001). After adjusting for confounders, “frequently or more severe” snoring was significantly associated with thinner total retinal thickness [β = −2.79 (95% CI: −5.27, −0.30)] and lower superficial RCP vessel density [β = −0.71 (95% CI: −1.19, −0.23)].

Conclusion: Our research showed self-reported snoring was associated with thinner retinal thickness and lower superficial RCP vessel density. The findings of our study emphasize the need for self-reported snoring assessments in determining retinal structure and microcirculation impairment.