bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locus Coeruleus Volume is Reduced in Early Parkinson Disease-Related Orthostatic Hypotension.
Authors: Beach Paul A. , Kurra Nithin , Hwang Kristy , Langley Jason , Hu Xiaoping , Huddleston Daniel E. 
Published: October 2021

Abstract
Background

Orthostatic hypotension (OH) is common in Parkinson disease (PD) and often coincident with cognitive impairment. The locus coeruleus (LC), a central autonomic and cognitive regulator, may be a common pathophysiologic link. Here we tested whether LC structural pathology, measured by neuromelanin-sensitive MRI, is associated with OH, cognition, and OH symptom presence (OHSx) in PD.
Methods

PD motor exam, orthostatic vital signs (OVS), and depression, anxiety, and fatigue symptom scales were measured in 62 patients. Automated segmentation of LC and substantia nigra pars compacta (SNc, control region) took place using 3T MRI-based 2D T1-weighted and neuromelanin-sensitive sequences. LC/SNc volumes (mm3) were compared between OH and no-OH patients (N=9 & 53) using MACOVA. One-tailed partial correlations (False discovery rate (FDR) corrected) between LC volume, OVS, and MoCA were measured. MANOVA tested for relationships between OHSx, LC/SNc volumes, OVS, and non-motor scales.
Results

LC, but not SNc, volumes were reduced in OH-patients, compared to no-OH (LC p=0.01; SNc p=0.44). LC volumes correlated with OVS (systolic blood pressure/SBP r=0.24, pFDR=0.043; diastolic/DBP r=0.25, pFDR=0.043; heart rate/HR r=-0.32, pFDR=0.024) and with MoCA (r=0.22, pFDR=0.043). OH-patients were more likely to endorse OHSx (Chi Sq. p=0.047). LC/SNc volumes were unrelated to OHSx but were associated with DBP change (F=4.3, p=0.043; SBP trended – F=3.8, p=0.055), and with greater depressive (F=6.6, p=0.012) and fatigue (F=5.13, p=0.027) symptoms.
Conclusions

This study supports LC as a neural substrate for OH and possibly cognitive decline in PD, but not OHSx, which were more associated with depressive and fatigue symptoms. A larger cohort of OH-patients is needed to validate these findings.
Synthesis and Numerical Analysis of Compliant devices – A Topology Optimization Approach for Mechanisms and Robotic Systems
Authors: Sathyanarayanamurthi Premanand , GOPAL ARUNKUMAR 
Published: October 2021

Abstract
The Topology Optimization design invariably shall be used in various applications like Aerojet designs, Aircraft Engineering designs and innovative systems for improving the efficiency of structure. The paper emphasizes more on general Topology Optimization design for a rectangular domain. The domain numerically analyzed with defined geometry setting and defined boundary conditions for finding the Stress and displacement. In this Topology Optimization Design synthesis, the result is suitable volume and mass reduction in the Aerojet application parts which further can be taken for Prototype development in 3D printing and experimentally test with safety characteristics and compares Objective functions chosen for design and development. The design can be used for other various automotive and aerospace devices based on deformation level and application of external forces. The Final destination of this design and development ends with passing Fatigue Endurance test cycle test pass condition in Aerojet and automotive vehicles in static and dynamic state.
Cerebrospinal Fluid Efflux Through Dynamic Paracellular Pores on Venule as a Missing Piece for the Image of Brain Drainage System
Authors: Dong Yaqiong , Xu Ting , Yuan Lan , Wang Yahan , Yu Siwang , Wang Zhi , Zhang Weiguang , He Weijiang , Yang Xiaoda 
Published: October 2021

Abstract
Background: The glymphatic system has been considered to contribute to a larger portion of parenchyma waste clearance and related to pathogenesis of many neural degenerative diseases such as the Alzheimer’s disease (AD). However, up to date, the key route for the efflux from perivascular spaces to the blood pool remains a mystery.Methods: BBB-impermeable fluorescent lanthanide probes of different size were first applied as cerebrospinal fluid (CSF)/interstitial fluid (ISF) tracers to quantitatively clarify the relative importance of different pathways to drain CSF/ISF solutes. The in vivo dynamic flows of subarachnoid CSF labeled with fluorescein isothiocyanate-dextran (4 kDa) tracers along brain blood vessels were observed under a two-photon confocal laser scanning microscope. Results: Three phasic process for the brain drainage was observed, in which the rapid efflux of ISF solutes with a time constant close to the CSF oscillation during sleep appeals for new routes from perivenuous spaces to the blood pool. Careful observation on the dynamic efflux in vivo revealed a novel drainage pathway in which CSF molecules converge into the bloodstream directly through dynamic trumpet-like pores (basolateral f＜8 μm; apical f＜2 μm) on the wall of brain venule in mice. Zn2+, an inducer of reconstruction of the tight junctions (TJs) in vascular endothelial cells, could facilitate the brain clearance of macromolecular ISF solutes. Deficit clearance of Aβ through the asymmetric pores on venule potentially causing perivascular space dilation was observed on the AD model mice.Conclusions: The novel asymmetric pore path through reconstruction of endothelial TJs on the wall of venule shall provide a key piece for ISF solutes to drainage from brain in very rapid pathway. The update image would help to understand the structure and the regulation of glymphatic clearance of brain metabolites such as Aβ in search for the solutions of neurodegenerative diseases.
microRNA-150-5p: A Novel Blood-Based Biomarker for Alzheimer’s Dementia with Good Correlation to Cognition, Cerebrospinal Fluid Amyloid-β, and Cerebral Atrophy
Authors: Chia Sook-Yoong , Vipin Ashwati , Ng Kok-Pin , Tu Haitao , Bommakanti Ananth , Wang Brian Zhiyang , Tan Yi Jayne , Zailan Fatin Zahra , Ng Adeline Su-Lyn , Ling Shuo-Chian , Okamura Katsutomo , Tan Eng-King , Kandiah Nagaendran , Zeng Li 
Published: October 2021

Abstract
Background: There is an urgent need for non-invasive, cost-effective biomarkers for Alzheimer’s disease (AD), such as blood-based biomarkers. It is not only to support clinical diagnosis of dementia, but also to allow for timely pharmacological and non-pharmacological interventions evaluation. The aim of this study is to identify and validate a novel blood-based microRNA (miRNA) biomarker for dementia of Alzheimer’s disease type (DAT). The miRNA correlations with AD pathology and AD clinical-radiological imaging were conducted.Methods: We conducted miRNA-sequencing (miRNA-Seq) using peripheral blood mononuclear cells (PBMCs) isolated from a discovery cohort comprising DAT, mild cognitive impairment (MCI), and healthy subject (HS). Identified miRNA was validated in an independent cohort. Correlation analysis evaluated the relationships between miRNA expression and DAT clinical measures, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, CSF Aβ1-42 and tau levels, and AD pattern cerebral atrophy. Furthermore, we conducted bioinformatics analysis and cell-based assay to identify miRNA target genes. Results: MiRNA-seq identified a distinct miRNA (miR-328-3p, miR-7706, and miR-150-5p) expression signature differentiating DAT from MCI and HS. qPCR analysis reveals that miR-150-5p was consistent with the miRNA-seq data and was further validated. Specifically, we found that miR-150-5p expression was significantly upregulated in DAT compared to MCI and HS, and discriminated DAT from MCI and HS with a high accuracy with AUC of 0.86 and 0.86, respectively. We further found that higher miR-150-5p levels correlated with clinical measures of DAT, including lower global cognitive scores of MMSE and MoCA, lower CSF Aβ1-42, and higher CSF tau. Interestingly, we observed that higher miR-150-5p levels is associated with the lower grey matter volumes in the medial temporal lobe, posterior cingulate cortex and precuneus. These regions implicated default mood network and executive control network regions that are important for AD brain atrophy. Furthermore, pathway analysis identified the targets of miR-150-5p to be enriched in the Wnt signalling pathway, including programmed cell death 4 (PDCD4). We further found that PDCD4 was downregulated in DAT blood and was downregulated by miR-150-5p at both transcriptional and protein levels.Conclusions: Our findings demonstrated that miR-150-5p is a reliable clinical blood-based biomarker for DAT.
Gestational Hypertension and Their Impact on Activin A Concentration of the Human Milk
Authors: Peila Chiara , Spada Elena , Coscia Alessandra , Sottemano Stefano , Fregnan Giulia , Barbagallo Ignazio , Livolti Giovanni , Galvano Fabio , Gazzolo Diego 
Published: October 2021

Abstract
Introduction It is known that Preeclampsia affects the lactogenesis, but literature data on the effects of this syndrome on the neurobiomarkers composition and Activin A of Human Milk of the lactating mother are not available. The aim of this study is to investigate the effects of this gestational pathology on Activin A levels, a neurobiomarker known to play an important role in the development and protection of the central nervous system.Methods The women recruited in the study were divided in two different study groups: preeclamptic or healthy women. All the breast milk samples were collected using the same procedure into sterile devices BPA-free. Activin A was quantified using an ELISA test. To investigate the effect of pathology in the Activin a concentration in the 3 phases, mixed linear model with unistructural covariance structure, mother as random effect, and fixed effects were performed.Results Activin A was detected in all samples. There were no significant differences between Preeclamptic mother and Normotensive women. The only significant effect is related to the HM phase: in particular, it is significant the difference between colostrum and mature milk (p<0.01).Conclusion There is not any significant difference in Activin A breast milk composition from hypertensive and normotensive women. This result allows us to affirm that breast milk beneficial properties are maintained even if gestational hypertension occurs.
Transcriptomic Analysis of Patients With Clinical Suspicion of Maturity-onset Diabetes of the Young (MODY) With a Negative Genetic Diagnosis
Authors: Vázquez-Mosquera María E. , González-Vioque Emiliano , Barbosa-Gouveia Sofía , Bellido-Guerrero Diego , Tejera-Pérez Cristina , Martinez-Olmos Miguel A. , Fernández-Pombo Antía , Castaño-González Luís A. , Chans-Gerpe Roi , Couce Maria L. 
Published: October 2021

Abstract
BackgroundThe personalized management of each type of Mature-onset diabetes of the young (MODY), a non-autoimmune monogenic form of diabetes mellitus, achieves both avoiding invasive therapies and better defining the patient's prognosis and reducing future misdiagnoses by performing a screening family. Positive genetic diagnosis is achieved in only around 50% of patients with clinical characteristics of this disease, which leads us to propose in this study to evaluate the diagnostic utility of transcriptomic analysis in patients with clinical suspicion of MODY but a negative genetic diagnosis using Nanostring nCounter technology.ResultsWe conducted transcriptomic analysis of 19 MODY-associated genes in peripheral blood samples from 19 patients and 8 healthy controls. Normalized gene expression was compared between patients and controls and correlated with each patient’s biochemical and clinical variables. Z-scores were calculated to identify significant changes in gene expression in patients versus controls. Only 7 of the genes analyzed were detected in peripheral blood. HADH expression was significantly lower in patients versus controls. Among patients with suspected MODY, GLIS3 expression was higher in obese versus non-overweight patients, and in patients aged <25 versus >25 years at diabetes onset. Significant alteration with respect to controls of any gene was observed in 31.6% of patients. ConclusionsAlthough blood does not appear to be an adequate sample for transcriptomic analysis of patients with suspected MODY, it does allow identification of potential molecular targets causing the disease in a considerable proportion of cases.
Reconstruction clipping of ruptured anterior circulation aneurysms via supraorbital lateral keyhole approach
Authors: Wu Yuzhang , Zhao Yan , Yu Shengping , Li Fan , Cai Shifei , Peng Chao , Wang Zhen , Yang Yifan , Wang Bangyue , Yang Xinyu 
Published: October 2021

Abstract
Background
Intracranial aneurysm(IA) is a serious disease.Analyze and review the cases of anterior circulation ruptured IA by supraorbital lateral keyhole approach, and summarize the experiences of this approach.
Methods
Retrospective analysis of 16 cases of ruptured anterior circulation IA in our department from January 2019 to June 2020, CT angiography (CTA) was performed before operation. Analyzing the IA’s parameters by 3D-CT reconstruction. The IA was clipped by supraorbital lateral keyhole approach combined with the 3D-skull reconstruction. Extraventricular drainage were performed before craniotomy. Intraoperative neurophysiological monitoring was performed during the operation. After operation, fluorescein angiography and vascular ultrasound were performed to check the clipping effect. Intracranial pressure monitor was performed postoperatively. CTA was reexamined one week after operation. The modified Rankin Scale (MRS) was performed 6 months after operation.
Results
There were 7 males (43.8%) and 9 females (56.2%) ,the average age is 52.3 years. Among them, 11 patients(68.8%) were anterior communicating artery aneurysms and 5 (31.2%) were middle cerebral artery aneurysms. All patients were out of hospital within 10 days without any death, without cerebral infarction, cerebrospinal fluid leakage and neurological impairments. About mRS score, after 6 months follow-up, 8 cases(50%) had 0 point, 4 cases (25%) had 1 point, 4 cases (25%) had 2 points.
Conclusions
For ruptured anterior circulation IA, the supraorbital lateral keyhole approach combined with ventricular drainage, intraoperative electrophysiological monitoring and intraoperative vascular ultrasound is a safe and minimally invasive treatment. The application of reconstruction clipping can reconstruct the diameter of parent vessel and reduce the recurrence rate of IA.
Digital Image Analysis of Spices and Condiments for Plant Taxonomic Studies
Authors: Khan Haider Iqbal , DAS MIRA RANI , MIA MA BASET 
Published: October 2021

Abstract
To address the contemporary demand of the world in the 21st century with the development of virtual technology, and to make the smart way of action with more efficiency, the department of Crop Botany, Bangabandhu Sheikh Mujibur Rahman Agricultural University (BSMRAU) have taken a step to launch a web-based computerized version of Digital Herbarium and Herbarium Museum of crop plants. This digital herbarium holds a large body of collections of images of special crops such as spices and condiments for improving academic and research capability which can be accessed anytime from anywhere in the world. Images can easily mirror and elucidate the characters that can be described theoretically. Photographic specimens can provide an important complement to herbarium collections by providing teaching and identify resources that are easily accessible to the community with digital herbarium. Digital image also guarantees instant access and increased user interaction as multiple people can work on a single model simultaneously and easily access information on descriptive details, published work, microscopic preparations, and nomenclature. The launched Digital Herbarium intends to make maximum use of primary research material to connect the research community and general public, including school children, and take care of public interest and enthusiasm for teaching spices and condiments.
Evaluation of Maxillary and Mandibular Growth Pattern Based on Cervical Vertebral Maturation in Japanese
Authors: Manabe Asuka , Ishida Takayoshi , Kanda Eiichiro , Ono Takashi 
Published: October 2021

Abstract
Appropriate evaluation of maxillofacial growth and development is important for effective orthodontic treatment. The evaluation of growth is not based on chronological age, but on the physiological age that is evaluated according to individual development. The cervical vertebral bone age is one approach to evaluate physiological age. In the present study, we evaluated the growth pattern of maxilla and mandible in Japanese patients using the age of the cervical vertebrae as an index. Lateral cephalometric radiographs taken before the start of the orthodontic treatment were traced to evaluate the age of the cervical vertebrae and mandible. Altogether, 400 patients were allocated to groups based on the cervical vertebral maturation stages (CVMS), namely, CVMS I to V, with 80 patients in each group. In this study, stratified random sampling was used to obtain the required samples. We measured ANS-PNS as an index of maxillary length, whereas Ar-Go as an index of mandibular height and Go-Pog as an index of mandibular length on the cephalograms. It was found that ANS-PNS increased significantly between CVMS II and CVMS III, while both Ar-Go and Go-Pog increased significantly between CVMS III and CVMS IV in men. On the other hand, such significant increases in consecutive stages were not found in women. Based on these observations, it was suggested that CVMS is effective in evaluating the growth pattern of the maxilla and mandible.
Endovascular Treatment of Acute MI Occlusions Due To Underlying Intracranial Atherosclerotic Severe Stenosis
Authors: Yan Yazhou , Du Li , He Xiliang , Huang Qinghai , Pan Yuan , Xin Tao 
Published: October 2021

Abstract
Objective: Endovascular treatment (EVT) for acute ischemic stroke with an occlusion of the M1 segment due to intracranial atherosclerotic severe stenosis (ICASS) remains challenging. This study aimed to evaluate the safety and efficacy of EVT for ICASS-related M1 acute occlusion.Methods: We retrospectively reviewed all patients with an ICASS-related M1 acute occlusion underwent EVT at our institution between January 2015 and December 2020. Clinical presentation, baseline characteristics, angiographic and clinical results, technical feasibility, perioperative complications, and follow-up results were evaluated.Results: Twenty-two patients with ICASS-related M1 acute occlusion were included. Eight patients (36.4%) received bridging therapy and the other 14 patients (63.6%) directly underwent EVT. Fifteen patients (68.2%) treated with balloon dilations and stenting as rescue treatment. Six patients (27.3%) received single balloon angioplasty and 5 of these patients treated with staged stenting. One case (4.5%) failed recanalization at the first EVT and successful revascularization was achieved a month later. The mean procedure time was 67.2±20.8 min. Successful revascularization (mTICI≥2b) was achieved in 95.5% (21/22) of patients. Perioperative complications developed in two patients (9.1%) including one hemorrhagic event and one thromboembolic event. Anangiographic follow-up was available in 20 patients (90.9%) at an average of 8.6±3.0 months. The degree of stenosis was worse (10%-30%) in 6 cases (30%) compared with the initial outcomes. The favorable outcomes (mRS≤2) at 3 months follow-up was achieved in 19 patients (86.4%).Conclusions: ICASS-related occlusion in the M1 segment often required a rescue therapy including balloon angioplasty with/without stenting, and this treatment strategy was safe and effective. But single balloon angioplasty at the first EVT generally cannot achieve satisfactory results and often needed staged stenting treatment.
An Ultrapotent Neutralizing Bispecific Antibody with Broad Spectrum Against SARS-CoV-2 Variants
Authors: Zhang Hui , Huang Haohui , Li Rong , Zhang Lu , Wang Zhiwei , Liang Shide , Li Jiaping , Chen Junyou , Su Huafei , Zheng Dandan , Su Ziqi , Wang Li , Deng Chunping , Pei Shujun , Zhu Shenghua , Li Chan , Yuan Yaochang , Yue Haitao , Wang Yanqun , Li Xiaobo , Liu Cuihua , Yu Jinchen , Li Shengfeng , Huang Xianming 
Published: October 2021

Abstract
Some variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are threatening our global efforts of herd immunity, novel and more efficacious agents are urgently needed. We have developed a bispecific antibody, 2022, which bonds with high affinity to two non-overlapping epitopes on the receptor-binding domain (RBD) simultaneously, blocks the binding of RBD to human angiotensin-converting enzyme 2 (ACE2), and potently neutralizes SARS-CoV-2 and all of the variants tested, including variants carrying mutations known to resist neutralizing antibodies approved under Emergency Use Authorization (EUA) and reduce the efficacy of existing vaccines. In a mouse model of SARS-CoV-2, 2022 showed strong prophylactic and therapeutic effects. A single administration of 2022 completely protected all mice from bodyweight loss, as compared with up to 20% loss of bodyweight in placebo treated mice, reduced the lung viral titers to undetectable in all mice treated with 2022 either prophylactically or therapeutically, as compared with around 1X105 pfu/g lung tissue in placebo treated mice. In summary, bispecific antibody 2022 showed potent binding and neutralizing activity across a variety of SARS-CoV-2 variants and could be an attractive weapon to combat the ongoing waves of the COVID-19 pandemic.
A Modified Hybrid Operation:The Retroperitoneoscopic Nephroureterectomy Without Intraoperative Patient Repositioning
Authors: Wu Zhou-Liang , Zhang Zhe , Li Zhi , Zhao Gang-Jian , Shen Chong , Zhang Yu , Zhan Xue-Jian , Jiang Zhang , Tian Da-Wei , Hu Hai-Long 
Published: October 2021

Abstract
Purpose: To describe the oncological safety and validity of the modified hybrid operation without intraoperative patient repositioning for upper urinary tract urothelial carcinoma (UTUC) patients. Materials and Methods: We collected and retrospectively analyzed the clinical data of 63 consecutive patients underwent the modified hybrid operation for localized UTUC at The Second Hospital of Tianjin Medical University between July 2018 and July 2019. Details of the modified operating technique were summarized and described. Results: All procedures were successful and no reposition or re-sterilization occurred during these operations. The operative time was 135 mins (IQR:125-145) and estimated blood loss was 35 ml (IQR:30-45.5), the time of distal ureter and bladder cuff resection was only 40 mins (IQR:35-47.5). No positive margins were found by pathological investigation. No complication related to the modified position was detected. Follow-up period after surgery was 24 months (IQR:19.5-27) and 12 cases (19.05%) had recurrence.Conclusion: The modified hybrid technique eliminated the need for patients repositioning during the extravesical bladder cuff excision and permitted the continuity of the operation. It minimizes the operative time and eliminates the distortion of the surgeon's lower back. This technique can be safely reproduced with surgical outcomes comparable to other established techniques.