bluuebunny/crossref_metadata_2025_split huggingface dataset:
18F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies
Authors: Ezura Michinori , Kikuchi Akio , Okamura Nobuyuki , Ishiki Aiko , Hasegawa Takafumi , Harada Ryuichi , Watanuki Shoichi , Funaki Yoshihito , Hiraoka Kotaro , Baba Toru , Sugeno Naoto , Yoshida Shun , Kobayashi Junpei , Kobayashi Michiko , Tano Ohito , Ishiyama Shun , Nakamura Takaaki , Nakashima Ichiro , Mugikura Shunji , Iwata Ren , Taki Yasuyuki , Furukawa Katsutoshi , Arai Hiroyuki , Furumoto Shozo , Tashiro Manabu , Yanai Kazuhiko , Kudo Yukitsuka , Takeda Atsushi , Aoki Masashi 
Published: December 2021

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters.Methods:18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke’s Cognitive Examination–Revised, and Frontal Assessment Battery, Unified Parkinson’s Disease Rating Scale Motor Score, and PSP Rating Scale.Results:18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP.Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.
Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy
Authors: Whatley Benjamin P. , Winston Joel S. , Allen Luke A. , Vos Sjoerd B. , Jha Ashwani , Scott Catherine A. , Smith April-Louise , Chowdhury Fahmida A. , Bomanji Jamshed B. , Lhatoo Samden D. , Harper Ronald M. , Diehl Beate 
Published: November 2021

Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET).Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS.Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex.Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP.
Abnormal Fractional Amplitude of Low-Frequency Fluctuation as a Potential Imaging Biomarker for First-Episode Major Depressive Disorder: A Resting-State fMRI Study and Support Vector Machine Analysis
Authors: Gao Yujun , Wang Xi , Xiong Zhenying , Ren Hongwei , Liu Ruoshi , Wei Yafen , Li Dongbin 
Published: December 2021

Objective: Major depressive disorder (MDD) is a psychiatric disorder with serious negative health outcomes; however, there is no reliable method of diagnosis. This study explored the clinical diagnostic value of the fractional amplitude of low-frequency fluctuation (fALFF) based on the support vector machine (SVM) method for the diagnosis of MDD.Methods: A total of 198 first-episode MDD patients and 234 healthy controls were involved in this study, and all participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning. Imaging data were analyzed with the fALFF and SVM methods.Results: Compared with the healthy controls, the first-episode MDD patients showed higher fALFF in the left mid cingulum, right precuneus, and left superior frontal gyrus (SFG). The increased fALFF in these three brain regions was positively correlated with the executive control reaction time (ECRT), and the increased fALFF in the left mid cingulum and left SFG was positively correlated with the 17-item Hamilton Rating Scale for Depression (HRSD-17) scores. The SVM results showed that increased fALFF in the left mid cingulum, right precuneus, and left SFG exhibited high diagnostic accuracy of 72.92% (315/432), 71.76% (310/432), and 73.84% (319/432), respectively. The highest diagnostic accuracy of 76.39% (330/432) was demonstrated for the combination of increased fALFF in the right precuneus and left SFG, along with a sensitivity of 84.34% (167/198), and a specificity of 70.51% (165/234).Conclusion: Increased fALFF in the left mid cingulum, right precuneus, and left SFG may serve as a neuroimaging marker for first-episode MDD. The use of the increased fALFF in the right precuneus and left SFG in combination showed the best diagnostic value.
Circulating microRNAs in Symptomatic and Asymptomatic Carotid Stenosis
Authors: Grosse Gerrit M. , Derda Anselm A. , Stauss Ricarda D. , Neubert Lavinia , Jonigk Danny D. , Kühnel Mark P. , Gabriel Maria M. , Schuppner Ramona , Wilhelmi Mathias , Bär Christian , Bauersachs Johann , Schrimpf Claudia , Thum Thomas , Weissenborn Karin 
Published: November 2021

Background: Specific microRNAs (miRs) have been implicated in the pathophysiology of atherosclerosis and may represent interesting diagnostic and therapeutic targets in carotid stenosis. We hypothesized that the levels of specific circulating miRs are altered in patients with symptomatic carotid stenosis (sCS) in comparison to those in patients with asymptomatic carotid stenosis (aCS) planned to undergo carotid endarterectomy (CEA). We also studied whether miR levels are associated with plaque vulnerability and stability over time after CEA.Methods: Circulating levels of vascular-enriched miR-92a, miR-126, miR-143, miR-145, miR-155, miR-210, miR-221, miR-222, and miR-342-3p were determined in 21 patients with sCS and 23 patients with aCS before CEA and at a 90-day follow-up. Transcranial Doppler ultrasound for detection of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed prior to CEA. Carotid plaques were histologically analyzed.Results: Mean levels of miRs were not considerably different between groups and were only marginally higher in sCS than aCS concerning miR-92a, miR-210, miR-145, and miR-143 with the best evidence concerning miR-92a. After adjustment for vascular risk factors and statin pre-treatment, the effect sizes remained essentially unchanged. At follow-up, however, these modest differences remained uncorroborated. There were no relevant associations between miR-levels and MES or histological plaque vulnerability features.Conclusions: This study does not provide evidence for strong associations between specific circulating miRs and symptomatic state in a collective of comprehensively characterized patients with carotid stenosis. Further work is needed to elucidate the role of circulating miRs as targets in advanced carotid atherosclerosis.
Cognitive Development and Brain Gray Matter Susceptibility to Prenatal Adversities: Moderation by the Prefrontal Cortex Brain-Derived Neurotrophic Factor Gene Co-expression Network
Authors: de Mendonça Filho Euclides José , Barth Barbara , Bandeira Denise Ruschel , de Lima Randriely Merscher Sobreira , Arcego Danusa Mar , Dalmaz Carla , Pokhvisneva Irina , Sassi Roberto Britto , Hall Geoffrey B. C. , Meaney Michael J. , Silveira Patricia Pelufo 
Published: November 2021

Background:Previous studies focused on the relationship between prenatal conditions and neurodevelopmental outcomes later in life, but few have explored the interplay between gene co-expression networks and prenatal adversity conditions on cognitive development trajectories and gray matter density.Methods:We analyzed the moderation effects of an expression polygenic score (ePRS) for the Brain-derived Neurotrophic Factor gene network (BDNF ePRS) on the association between prenatal adversity and child cognitive development. A score based on genes co-expressed with the prefrontal cortex (PFC) BDNF was created, using the effect size of the association between the individual single nucleotide polymorphisms (SNP) and the BDNF expression in the PFC. Cognitive development trajectories of 157 young children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort were assessed longitudinally in 4-time points (6, 12, 18, and 36 months) using the Bayley-II mental scales.Results:Linear mixed-effects modeling indicated that BDNF ePRS moderates the effects of prenatal adversity on cognitive growth. In children with high BDNF ePRS, higher prenatal adversity was associated with slower cognitive development in comparison with those exposed to lower prenatal adversity. Parallel-Independent Component Analysis (pICA) suggested that associations of expression-based SNPs and gray matter density significantly differed between low and high prenatal adversity groups. The brain IC included areas involved in visual association processes (Brodmann area 19 and 18), reallocation of attention, and integration of information across the supramodal cortex (Brodmann area 10).Conclusion:Cognitive development trajectories and brain gray matter seem to be influenced by the interplay of prenatal environmental conditions and the expression of an important BDNF gene network that guides the growth and plasticity of neurons and synapses.
Subjective Cognitive Complaints in Newly-Diagnosed Parkinson’s Disease With and Without Mild Cognitive Impairment
Authors: Pan Chenxi , Ren Jingru , Hua Ping , Yan Lei , Yu Miao , Wang Yajie , Zhou Gaiyan , Zhang Ronggui , Chen Jiu , Liu Weiguo 
Published: November 2021

Background: Subjective cognitive complaints (SCCs) and mild cognitive impairment (MCI) are common among patients with Parkinson’s disease (PD). However, the relationship between SCCs and MCI is not well understood. Herein, we aimed to investigate whether there are any differences in the prevalence and risk factors of SCCs between early PD patients with and without MCI.Methods: Overall, 108 newly diagnosed, untreated PD patients underwent comprehensive neuropsychological assessments. PD patients with mild cognitive impairment (PD-MCI) were diagnosed according to the MCI level II criteria. Furthermore, SCCs were measured with the Cognitive Complaints Interview (CCI). Logistic regression analysis, after adjusting for confounding variable, was performed in order to investigate risk factors of SCCs in PD-MCI patients and PD patients with normal cognition (PD-NC).Results: Furthermore, 42 (42.3%) participants reported SCCs and 53 (53.5%) participants were diagnosed with PD-MCI. The prevalence of SCCs in PD-MCI and PD-NC participants was 30.3% and 12.1%, respectively. Logistic regression analyses revealed that the presence of SCCs in PD-MCI group was significantly associated with Non-Motor Symptoms Questionnaire (NMSQ) score (OR = 1.340, 95%CI = 1.115−1.610, p = 0.002), while the presence of SCCs in PD-NC group was significantly associated with time of Stroop Color-Word Test card C (OR = 1.050, 95%CI = 1.009−1.119, p = 0.016).Conclusion: SCCs are frequent among patients with early PD. The prevalence and risk factor of SCCs are distinct in PD with and without MCI. These findings suggest that SCCs in early PD with different cognitive status appear to have different pathogenicity.
Pre-diagnosis Cruciferous Vegetables and Isothiocyanates Intake and Ovarian Cancer Survival: A Prospective Cohort Study
Authors: Wei Yi-Fan , Hao Ying-Ying , Gao Song , Li Xiu-Qin , Liu Fang-Hua , Wen Zhao-Yan , Wang Han-Yuan , Zhang Shuang , Yan Shi , Luan Meng , Zhao Yu-Hong , Gong Ting-Ting , Wu Qi-Jun 
Published: November 2021

Background: The associations of the consumption of cruciferous vegetables (CVs) and their bioactive components, isothiocyanates (ITCs), with ovarian cancer (OC) mortality have been unclear, owing to limited studies and inconsistent findings. To date, no studies have evaluated these associations among Chinese patients with OC. This study aims to provide more evidence indicating the relationships of pre-diagnosis CVs and ITC intake with OC survival.Methods: We examined the associations of pre-diagnosis CV and ITC intake with OC mortality in a hospital-based cohort (n = 853) of Chinese patients with epithelial OC between 2015 and 2020. Pre-diagnosis dietary information was evaluated with a validated food frequency questionnaire. Deaths were ascertained until March 31, 2021 via medical records and active follow-up. The associations were examined with the Cox proportional hazards model, adjusted for potential confounders, and stratified by menopausal status, residual lesions, histological type, and body mass index (BMI).Results: During a median follow-up of 37.2 months (interquartile: 24.7–50.2 months), we observed 130 deaths. The highest tertile of total CV intake was associated with better survival than the lowest tertile intake [hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.33–0.98, p trend &lt; 0.05]. In addition, higher intake of ITCs from CVs was associated with better survival (HRT3VS.T1 = 0.59, 95% CI = 0.36–0.99, p trend = 0.06). Significant inverse associations were also observed for subgroup analyses stratified by menopausal status, residual lesions, histological type, and BMI, although not all associations showed statistical significance.Conclusion: Increasing pre-diagnosis consumption of CVs and ITCs was strongly associated with better survival in patients with OC.
Development and Validation of Prognostic Nomogram in Patients With WHO Grade III Meningioma: A Retrospective Cohort Study Based on SEER Database
Authors: Jia Zetian , Yan Yaqi , Wang Jiuxin , Yang He , Zhan Haihua , Chen Qian , He Yawei , Hu Yuhua 
Published: December 2021

IntroductionWorld Health Organization (WHO) Grade III meningioma is a central nervous system tumor with a poor prognosis. In this retrospective cohort study, the authors constructed a nomogram for predicting the prognosis of WHO Grade III meningioma.MethodsThe patients of this nomogram were based on the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. All patients were randomly divided into a development cohort (964 patients) and a validation cohort (410 patients) in a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression was used to screen the predictors. The Cox hazards regression model was constructed and the prognosis was visualized by nomogram. The performance of the prognostic nomogram was determined by consistency index (C-index), clinical net benefit, and calibration.ResultsEight variables were included in the nomogram: gender, race, age at diagnosis, histology, tumor site, tumor size, laterality, and surgical method. The C-index of the training set and verification set were 0.654 and 0.628. The calibration plots showed that the nomogram was in good agreement with the actual observation. The clinical decision curve indicates that the nomogram has a good clinical net benefit in WHO Grade III meningioma.ConclusionsA prognostic nomogram of a large cohort of WHO Grade III meningioma was established and verified based on the SEER database. The nomogram we established may help clinicians provide personalized treatment services and clinical decisions for patients.
Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers
Authors: Okuma Hitomi Sumiyoshi , Yonemori Kan , Kojima Yuki , Tanioka Maki , Sudo Kazuki , Noguchi Emi , Hijioka Susumu , Wakakuwa Keiko , Kato Ken , Hirakawa Akihiro , Kuchiba Aya , Kubo Takashi , Ichikawa Hitoshi , Yoshida Akihiko , Yatabe Yasushi , Nakamura Kenichi , Mano Hiroyuki , Yamamoto Noboru , Fujiwara Yasuhiro 
Published: November 2021

PurposePatients with advanced/relapsed rare cancers have few treatment options. Analysis of circulating tumor DNA in plasma may identify actionable genomic biomarkers using a non-invasive approach.Patients and MethodsRare cancer patients underwent prospective plasma-based NGS testing. Tissue NGS to test concordance was also conducted. Plasma DNA alterations were assessed for incidence, functional impact, therapeutic implications, correlation to survival, and comparison with tissue NGS.ResultsNinety-eight patients were analyzed. Diseases included soft-tissue sarcoma, ovarian carcinoma, and others. Mean turn-around-time for results was 9.5 days. Seventy-six patients had detectable gene alterations in plasma, with a median of 2.8 alterations/patient. Sixty patients had a likely pathogenic alteration. Five received matched-therapy based on plasma NGS results. Two developed known resistance mutations while on targeted therapy. Patients with an alteration having VAF ≥5% had a significantly shorter survival compared to those of lower VAF. Tissue NGS results from eleven of 22 patients showed complete or partial concordance with plasma NGS.ConclusionPlasma NGS testing is less invasive and capable of identifying alterations in advanced rare cancers in a clinically meaningful timeframe. It should be further studied as a prospective enrollment assay in interventional studies for patients with rare advanced stage cancers.Clinical Registration[https://www.umin.ac.jp/ctr/index-j.htm], identifier UMIN000034394.
Prostate Cancer Gleason Score From Biopsy to Radical Surgery: Can Ultrasound Shear Wave Elastography and Multiparametric Magnetic Resonance Imaging Narrow the Gap?
Authors: Wei Cheng , Zhang Yilong , Zhang Xinyu , Ageeli Wael , Szewczyk-Bieda Magdalena , Serhan Jonathan , Wilson Jennifer , Li Chunhui , Nabi Ghulam 
Published: November 2021

ObjectivesTo investigate the impact of ultrasound shear wave elastography (USWE) and multiparametric magnetic resonance imaging (mpMRI) in predicting a change in biopsy-assigned Gleason Score (GS) after radical surgery for localised prostate cancer (PCa).MethodA total of 212 men opting for laparoscopic radical prostatectomy (LRP) between September 2013 and June 2017 were recruited into this study. All the participants had 12-core transrectal ultrasound (TRUS) biopsies and imaging using USWE and mpMRI before radical surgery. The predictive accuracy for imaging modalities was assessed in relation to upgrading and downgrading of PCa GS between the biopsies and radical prostatectomy using Student’s t-test and multivariable logistic regression analyses. A decision analysis curve was constructed assessing the impact of nomogram on clinical situations using different thresholds of upgrading probabilities.ResultsMost GS 6 diseases on biopsies were upgraded on radical surgery (37/42, 88.1%). Major downgrading was seen in GS 8 category of disease (14/35; 37.1%), whereas no alteration was observed in GS 7 on biopsies in most men (55/75; 73.3%). In univariate analysis, higher preoperative prostate-specific antigen (PSA) (p = 0.001), higher prostate-specific antigen density (PSAD) (p = 0.002), stiffer USWE lesions (p = 0.009), and higher prostate imaging–reporting and data system (PIRADS) (p = 0.002) on mpMRI were significant predictors of upgrading. In multivariate logistic regression analyses, only PSA (p = 0.016) and USWE-measured tissue stiffness (p = 0.029) showed statistical significance in predicting upgrading.ConclusionsMeasurement of tissue stiffness using USWE in clinically localised PCa can predict upgrading of GS and has the potential to improve patient management options.
Cohort Profile: The Socioeconomic Consequences in Adult Life After Childhood Cancer in Scandinavia (SALiCCS) Research Programme
Authors: Erdmann Friederike , Frederiksen Line Elmerdahl , Mogensen Hanna , Pedersen Camilla , Mader Luzius , Talbäck Mats , Bautz Andrea , Hirvonen Elli , Kyrönlahti Anniina , Korhonen Liisa Maria , Hasle Henrik , Malila Nea , Madanat-Harjuoja Laura-Maria , Feychting Maria , Winther Jeanette Falck 
Published: December 2021

IntroductionThe growing number of survivors of childhood cancer, with many years of life ahead, demonstrates the increasing clinical and public health relevance of investigating the risks of social and socioeconomic impairment after a childhood cancer diagnosis and the life-saving treatment. To enrich understanding of the mental, social and socioeconomic difficulties that childhood cancer survivors may face during their life-course, identify particularly vulnerable survivors and overcome the limitations of previous research, we initiated the Socioeconomic Consequences in Adult Life after Childhood Cancer in Scandinavia (SALiCCS) research programme.MethodsThis Nordic cross-border research programme is a collaboration between the Danish Cancer Society, the Finnish Cancer Registry and Karolinska Institutet to investigate a broad range of mental, social and socioeconomic conditions in long-term childhood cancer survivors in Denmark, Finland and Sweden. SALiCCS is based on a registry-based matched cohort design, comprising five-year survivors of cancer diagnosed at ages 0–19 years (1971–2008 in Denmark, 1971–2009 in Finland, 1971–2011 in Sweden), age-, sex- and country-matched population comparisons and sibling comparisons who were followed over time. Outcomes of interest included mental disorders, educational achievements, employment and profession, family life and the need of social security benefits. Individual-level data linkage among various national registries provided the data for the research programme.ResultsThe SALiCCS core population comprises 21,292 five-year survivors, 103,303 population comparisons and 29,644 siblings as a second comparison group. The most common diagnoses in survivors were central nervous system tumours, leukaemias and lymphomas.DiscussionSALiCCS is the largest, most comprehensive population-based research initiative in this field, based on high-quality registry data with minimal risk of bias. The findings will be informative for evidence-based survivorship care targeting not only somatic late effects but also psychosocial impairments.