bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain function mediates the association between low vitamin D and neurocognitive status in female patients with major depressive disorder
Authors: Zhao Wenming , Zhu Dao-min , Li Qian , Xu Xiaotao , Zhang Yu , Zhang Cun , Zhu Jiajia , Yu Yongqiang 
Published: April 2022

AbstractBackgroundVitamin D is engaged in various neural processes, with low vitamin D linked to depression and cognitive dysfunction. There are gender differences in depression and vitamin D level. However, the relationship between depression, gender, vitamin D, cognition, and brain function has yet to be determined.MethodsOne hundred and twenty-two patients with major depressive disorder (MDD) and 119 healthy controls underwent resting-state functional MRI and fractional amplitude of low-frequency fluctuations (fALFF) was calculated to assess brain function. Serum concentration of vitamin D (SCVD) and cognition (i.e. prospective memory and sustained attention) were also measured.ResultsWe found a significant group-by-gender interaction effect on SCVD whereby MDD patients showed a reduction in SCVD relative to controls in females but not males. Concurrently, there was a female-specific association of SCVD with cognition and MDD-related fALFF alterations in widespread brain regions. Remarkably, MDD- and SCVD-related fALFF changes mediated the relation between SCVD and cognition in females.ConclusionApart from providing insights into the neural mechanisms by which low vitamin D contributes to cognitive impairment in MDD in a gender-dependent manner, these findings might have clinical implications for assignment of female patients with MDD and cognitive dysfunction to adjuvant vitamin D supplementation therapy, which may ultimately advance a precision approach to personalized antidepressant choice.
Research on control method of upper limb exoskeleton based on mixed perception model
Authors: Wang WenDong , Zhang JunBo , Kong Dezhi , Su Shibin , Yuan XiaoQing , Zhao Chengzhi 
Published: April 2022

AbstractAs one of the research hotspots in the field of rehabilitation robotics, the upper limb exoskeleton robot has been widely used in the field of rehabilitation. However, the existing methods cannot comprehensively and accurately reflect the motion state of patients, which may lead to overtraining and secondary injury of patients in the process of rehabilitation training. In this paper, an upper limb exoskeleton control method based on mixed perception model of motion intention and intensity is proposed, which is based on the 6 degree-of-freedom upper limb rehabilitation exoskeleton in the laboratory. First, the kinematic information and heart rate information in the rehabilitation process of patients are collected, corresponding to patients’ motion intention and motion intensity, and fused to obtain the mixed perception vector. Second, the motion perception model based on long short-term memory neural network is established to realize the prediction of upper limb motion trajectory of patients and compared with back-propagation neural network to prove its effectiveness. Finally, the control system is built, and both offline and online test of the control method proposed are implemented. The experimental results show that the method can achieve comprehensive motion state perception of patients, realize real-time and accurate prediction trajectory according to human motion intention and intensity. The average prediction accuracy is 95.3%, and predicted joint angle error is less than 5 degrees. Therefore, the control method based on mixed perception model has good robustness and universality, which provides a new method for the active control of upper limb exoskeleton.
Preliminary assessment of paediatric electrophysiology cardiac implantable electronic device resources around the world
Authors: Gonzalez Corcia M Cecilia , Cohen Mitchell I , Paul Thomas , Skinner Jonathan R , Shah Maully 
Published: April 2022

AbstractBackground:The Pediatric and Congenital Electrophysiology Society (PACES) is a global organisation committed to the care of children and adults with CHD and arrhythmias.Objective:To evaluate the global needs and potential inequities as it relates to cardiac implantable electronic devices.Methods:ARROW (Assessment of Rhythm Resources arOund the World) is an online survey about cardiac implantable electronic devices, sent electronically to physicians within the field of Cardiology, Pediatric Cardiology, Electrophysiology and Pediatric Electrophysiology.Results:ARROW received 42 responders from 28 countries, 50% from low-/middle-income regions. The main differences between low-/middle- and high-income regions include availability of expertise on paediatric electrophysiology (50% versus 93%, p < 00.5) and possibility to perform invasive procedures (35% versus 93%, p < 0.005). Implant of devices in low-income areas relies significantly on patient’s resources (71%). The follow-up of the devices is on the hands of paediatric cardiologist/electrophysiologist in higher resources centres (93% versus 50%, p < 0.05).Conclusions:The ARROW survey represents an initial assessment of the geographical characteristics in the field of Pediatric Electrophysiology. The next step is to make this “state of the art” more extensive to other aspects of the expertise. The relevance of collecting this data before the World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) in 2023 in Washington DC was emphasised in order to share the resulting information with the international community and set a plan of action to assist the development of arrhythmia services for children within developing regions of the world.
2‐D Analytical P‐to‐S and S‐to‐P Scattered Wave Finite Frequency Kernels
Authors: Harmon Nicholas , Rychert Catherine A. , Xie Yujiang , Bogiatzis Petros 
Published: April 2022

AbstractScattered wave imaging provides a powerful tool for understanding Earth's structure. The development of finite frequency kernels for scattered waves has the potential for improving the resolution of both the structure and magnitude of discontinuities in S‐wave velocity. Here we present a 2‐D analytical expression for teleseismic P‐to‐S and S‐to‐P scattered wave finite‐frequency kernels for a homogeneous medium. We verify the accuracy of the kernels by comparing to a spectral element method kernel calculated using SPECFEM2D. Finally, we demonstrate the ability of the kernels to recover seismic velocity discontinuities with a variety of shapes including a flat discontinuity, a discontinuity with a sharp step, a discontinuity with a smooth bump, and an undulating discontinuity. We compare the recovery using the kernel approach to expected recovery assuming the classical common conversion point (CCP) stacking approach. We find that the P‐to‐S kernel increases recovery of all discontinuity structures in comparison to CCP stacking especially for the shallowest discontinuity in the model. The S‐to‐P kernel is less successful but can be useful for recovering the curvature of shallow discontinuity undulations. Finally, although we observe some variability in the amplitude of the kernels along the discontinuities, the kernels show some potential for recovering the magnitude of the velocity contrast across a discontinuity.
Initial Response of Nightside Auroral Currents to a Sudden Commencement: Observations of Electrojet and Substorm Onset
Authors: Zhou Yun‐Liang , Lühr Hermann 
Published: April 2022

AbstractStorm sudden commencements (SSC) often precede geomagnetic storms. Commonly, it takes some hours from the step‐like change that marks the SSC to the start of the magnetic storm activity. In a subset of cases, however, auroral activity starts almost instantaneously after the SSC. To the authors knowledge, the conditions that enable this rapid activation have not been investigated in detail before. Here we consider all the sudden commencements (SC) during the years 2000–2020. Our focus is on the initial response of the auroral currents on the nightside. For that purpose, we make use of the IMAGE Magnetometer Network in Fennoscandia. In about 30% of SC events an initial activation of the westward electrojet is observed. Magnetic deflections of the northward component, surpassing frequently 1,000 nT, are observed only 4 min after the SC. These intense westward currents, flowing typically in narrow channels of 1°–2° latitudinal width, last some 10 min. The electrojets are conjugate to regions in the magnetosphere near geostationary orbits. In several cases geomagnetic substorm onsets are observed about 30 min after the SC. These start typically at fairly high latitude, around 71° magnetic latitude. This is an indication for rather quiet conditions preceding the onset. The magnetic pulse of the SC seems to play an important role in initiating the strong electrojets and the substorms. These initial activities are of relevance for space weather effects because of their strong and rapid variations. This paper provides detailed observations of the initial auroral activity following some SCs.
Blockade of PD-L1/PD-1 signaling promotes osteo-/odontogenic differentiation through Ras activation
Authors: Jeon So Mi , Lim Je Sun , Park Su Hwan , Kim Hyung Joon , Kim Hyung-Ryong , Lee Jong-Ho 
Published: April 2022

AbstractThe programmed cell death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) deliver inhibitory signals to regulate immunological tolerance during immune-mediated diseases. However, the role of PD-1 signaling and its blockade effect on human dental pulp stem cells (hDPSCs) differentiation into the osteo-/odontogenic lineage remain unknown. We show here that PD-L1 expression, but not PD-1, is downregulated during osteo-/odontogenic differentiation of hDPSCs. Importantly, PD-L1/PD-1 signaling has been shown to negatively regulate the osteo-/odontogenic differentiation of hDPSCs. Mechanistically, depletion of either PD-L1 or PD-1 expression increased ERK and AKT phosphorylation levels through the upregulation of Ras enzyme activity, which plays a pivotal role during hDPSCs osteo-/odontogenic differentiation. Treatment with nivolumab (a human anti-PD-1 monoclonal antibody), which targets PD-1 to prevent PD-L1 binding, successfully enhanced osteo-/odontogenic differentiation of hDPSCs through enhanced Ras activity-mediated phosphorylation of ERK and AKT. Our findings underscore that downregulation of PD-L1 expression accompanies during osteo-/odontogenic differentiation, and hDPSCs-intrinsic PD-1 signaling inhibits osteo-/odontogenic differentiation. These findings provide a significant basis that PD-1 blockade could be effective immunotherapeutic strategies in hDPSCs-mediated dental pulp regeneration.
Aβ profiles generated by Alzheimer’s disease causing PSEN1 variants determine the pathogenicity of the mutation and predict age at disease onset
Authors: Petit Dieter , Fernández Sara Gutiérrez , Zoltowska Katarzyna Marta , Enzlein Thomas , Ryan Natalie S. , O’Connor Antoinette , Szaruga Maria , Hill Elizabeth , Vandenberghe Rik , Fox Nick C. , Chávez-Gutiérrez Lucía 
Published: April 2022

AbstractFamilial Alzheimer’s disease (FAD), caused by mutations in Presenilin (PSEN1/2) and Amyloid Precursor Protein (APP) genes, is associated with an early age at onset (AAO) of symptoms. AAO is relatively consistent within families and between carriers of the same mutations, but differs markedly between individuals carrying different mutations. Gaining a mechanistic understanding of why certain mutations manifest several decades earlier than others is extremely important in elucidating the foundations of pathogenesis and AAO. Pathogenic mutations affect the protease (PSEN/γ-secretase) and the substrate (APP) that generate amyloid β (Aβ) peptides. Altered Aβ metabolism has long been associated with AD pathogenesis, with absolute or relative increases in Aβ42 levels most commonly implicated in the disease development. However, analyses addressing the relationships between these Aβ42 increments and AAO are inconsistent. Here, we investigated this central aspect of AD pathophysiology via comprehensive analysis of 25 FAD-linked Aβ profiles. Hypothesis- and data-driven approaches demonstrate linear correlations between mutation-driven alterations in Aβ profiles and AAO. In addition, our studies show that the Aβ (37 + 38 + 40) / (42 + 43) ratio offers predictive value in the assessment of ‘unclear’ PSEN1 variants. Of note, the analysis of PSEN1 variants presenting additionally with spastic paraparesis, indicates that a different mechanism underlies the aetiology of this distinct clinical phenotype. This study thus delivers valuable assays for fundamental, clinical and genetic research as well as supports therapeutic interventions aimed at shifting Aβ profiles towards shorter Aβ peptides.
Clinical prediction models in psychiatry: a systematic review of two decades of progress and challenges
Authors: Meehan Alan J. , Lewis Stephanie J. , Fazel Seena , Fusar-Poli Paolo , Steyerberg Ewout W. , Stahl Daniel , Danese Andrea 
Published: April 2022

AbstractRecent years have seen the rapid proliferation of clinical prediction models aiming to support risk stratification and individualized care within psychiatry. Despite growing interest, attempts to synthesize current evidence in the nascent field of precision psychiatry have remained scarce. This systematic review therefore sought to summarize progress towards clinical implementation of prediction modeling for psychiatric outcomes. We searched MEDLINE, PubMed, Embase, and PsychINFO databases from inception to September 30, 2020, for English-language articles that developed and/or validated multivariable models to predict (at an individual level) onset, course, or treatment response for non-organic psychiatric disorders (PROSPERO: CRD42020216530). Individual prediction models were evaluated based on three key criteria: (i) mitigation of bias and overfitting; (ii) generalizability, and (iii) clinical utility. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used to formally appraise each study’s risk of bias. 228 studies detailing 308 prediction models were ultimately eligible for inclusion. 94.5% of developed prediction models were deemed to be at high risk of bias, largely due to inadequate or inappropriate analytic decisions. Insufficient internal validation efforts (within the development sample) were also observed, while only one-fifth of models underwent external validation in an independent sample. Finally, our search identified just one published model whose potential utility in clinical practice was formally assessed. Our findings illustrated significant growth in precision psychiatry with promising progress towards real-world application. Nevertheless, these efforts have been inhibited by a preponderance of bias and overfitting, while the generalizability and clinical utility of many published models has yet to be formally established. Through improved methodological rigor during initial development, robust evaluations of reproducibility via independent validation, and evidence-based implementation frameworks, future research has the potential to generate risk prediction tools capable of enhancing clinical decision-making in psychiatric care.
The effect of menaquinone-7 supplementation on dp-ucMGP, PIVKAII, inflammatory markers, and body composition in type 2 diabetes patients: a randomized clinical trial
Authors: Karamzad Nahid , Faraji Esmaeil , Adeli Shaghayegh , Sullman Mark J. M. , Pourghassem Gargari Bahram 
Published: April 2022

AbstractBackgroundType 2 diabetes mellitus (T2DM) is a common disorder that is characterized by chronic hyperglycemia and chronic inflammation, which also have a reinforcing effect on each other. The present research studied the effects of menaquinone (MK-7) supplementation on serum dp-ucMGP (dephospho uncarboxylated Matrix Gla Protein), PIVKAII (Prothrombin Induced by Vitamin K Absence), inflammatory markers and body composition indices in type 2 diabetes mellitus (T2DM) patients.MethodsThis 12-week double-blind placebo-controlled randomized clinical trial allocated 60 T2DM patients equally into a MK-7 (200 mcg/day) group or a placebo group. All patients also received dietary advice at the beginning of study and their dietary intakes were checked using a 3-day food record. The body composition of each patient was also measured and their vitamin K status was assessed using the ELISA method to measure serum dp-ucMGP and PIVKAII. In addition, inflammatory status indices were also measured, including hsCRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6) and TNF-α (tumor necrosis factor alpha). All measurements were made both before and after the intervention period.ResultsIn total 45 patients completed the trial (MK-7 group = 23 and placebo group = 22). The calorie and macronutrient intake of the two groups were similar pre and post intervention. There were statistically significant increases in dietary vitamin K intake for both groups over the course of the study (p < 0.05), but the intergroup differences were not significant. The body composition indices (i.e., body fat percentage, fat mass, fat free mass, muscle mass, bone mass and total body water) were not significantly different between groups or across the trial. The serum levels of the vitamin K markers, PIVKAII and dp-ucMGP, decreased significantly in the MK-7 group over the course of the study (p < 0.05), but there was no decrease in the placebo group. However, after adjusting for the baseline levels and changes in vitamin K intake, the between group differences were only significant for PIVKAII (p < 0.05). Following the intervention, the serum levels of the inflammatory markers (hsCRP, IL-6, and TNF-α) were significantly lower in the MK-7 group (p < 0.05), but not in the placebo group. However, the between group differences in the inflammatory markers were not statistically significant.ConclusionsAlthough further studies are needed, it appears that MK-7 supplementation can be effective in improving PIVKAII levels, but not for improving dp-ucMGP, inflammatory status or the body composition indices of T2DM patients.Trial registration numberThis study was prospectively registered at the Iranian Registry of Clinical Trials on the 20th of May 2019 (ID: IRCT20100123003140N22).
Clinical and translational values of spatial transcriptomics
Authors: Zhang Linlin , Chen Dongsheng , Song Dongli , Liu Xiaoxia , Zhang Yanan , Xu Xun , Wang Xiangdong 
Published: April 2022

AbstractThe combination of spatial transcriptomics (ST) and single cell RNA sequencing (scRNA-seq) acts as a pivotal component to bridge the pathological phenomes of human tissues with molecular alterations, defining in situ intercellular molecular communications and knowledge on spatiotemporal molecular medicine. The present article overviews the development of ST and aims to evaluate clinical and translational values for understanding molecular pathogenesis and uncovering disease-specific biomarkers. We compare the advantages and disadvantages of sequencing- and imaging-based technologies and highlight opportunities and challenges of ST. We also describe the bioinformatics tools necessary on dissecting spatial patterns of gene expression and cellular interactions and the potential applications of ST in human diseases for clinical practice as one of important issues in clinical and translational medicine, including neurology, embryo development, oncology, and inflammation. Thus, clear clinical objectives, designs, optimizations of sampling procedure and protocol, repeatability of ST, as well as simplifications of analysis and interpretation are the key to translate ST from bench to clinic.
Examining allostatic load, neighborhood socioeconomic status, symptom burden and mortality in multiple myeloma patients
Authors: Obeng-Gyasi Samilia , Graham Noah , Kumar Shaji , Lee Ju-Whei , Jacobus Susanna , Weiss Matthias , Cella David , Zhao Fengmin , Ip Edward H. , O’Connell Nathaniel , Hong Fangxin , Peipert Devin J. , Gareen IIana. F. , Timsina Lava R. , Gray Robert , Wagner Lynne I. , Carlos Ruth C. 
Published: April 2022

AbstractThe objective of this study is to examine the association between neighborhood socioeconomic status (nSES) and baseline allostatic load (AL) and clinical trial endpoints in patients enrolled in the E1A11 therapeutic trial in multiple myeloma (MM). Study endpoints were symptom burden (pain, fatigue, and bother) at baseline and 5.5 months, non-completion of induction therapy, overall survival (OS) and progression-free survival (PFS). Multivariable logistic and Cox regression examined associations between nSES, AL and patient outcomes. A 1-unit increase in baseline AL was associated with greater odds of high fatigue at baseline (adjusted OR [95% CI] = 1.21 [1.08–1.36]) and a worse OS (adjusted hazard ratio, [95% CI] = 1.21 [1.06–1.37]). High nSES was associated with worse baseline bother (middle OR = 4.22 [1.11–16.09] and high 4.49 [1.16–17.43]) compared to low nSES. There was no association between AL or nSES and symptom burden at 5.5 months, non-completion of induction therapy or PFS. Additionally, there was no association between nSES and OS. AL may have utility as a predictive marker for OS among patients with MM and may allow individualization of treatment. Future studies should standardize and validate AL patients with MM.
Loss of neurodevelopmental-associated miR-592 impairs neurogenesis and causes social interaction deficits
Authors: Fu Yu , Zhou Yang , Zhang Yuan-Lin , Zhao Bo , Zhang Xing-Liao , Zhang Wan-Ting , Lu Yi-Jun , Lu Aiping , Zhang Jun , Zhang Jing 
Published: April 2022

AbstractmicroRNA-592 (miR-592) has been linked to neurogenesis, but the influence of miR-592 knockout in vivo remains unknown. Here, we report that miR-592 knockout represses IPC-to-mature neuron transition, impairs motor coordination and reduces social interaction. Combining the RNA-seq and tandem mass tagging-based quantitative proteomics analysis (TMT protein quantification) and luciferase reporter assays, we identified MeCP2 as the direct targetgene of miR-592 in the mouse cortex. In Tg(MECP2)mice, lipofection of miR-592 efficiently reducedMECP2expression in the brains of Tg(MECP2)mice at E14.5. Furthermore, treatment with miR-592 partially ameliorated the autism-like phenotypes observed in adult Tg(MECP2) mice. The findings demonstrate that miR-592 might play a novel role in treating the neurodevelopmental-associated disorder.