-Linked Parkinson Syndrome in Female Heterozygotes Is Associated With PET-Detectable Tau Pathology.

Background And Objectives: A previous postmortem study of men with Christianson syndrome, a disorder caused by loss-of-function mutations in the gene , reported a mechanistic link between pathologic tau accumulation and progressive symptoms such as cerebellar atrophy and cognitive decline. This study aimed to characterize the relationships between neuropathologic manifestations and tau accumulation in heterozygous women with mutation.

Methods: We conducted a multimodal neuroimaging and plasma biomarker study on 3 middle-aged heterozygous women with mutations (proband 1: mid-50s; proband 2: early 50s; proband 3: mid-40s) presenting with progressive extrapyramidal symptoms.

Comparison between DSQIID total / sub-item scores and plasma p-tau elevation in adults with Down's syndrome.

The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) is an appropriate screening tool for detecting dementia in Down's syndrome patients. However, whether this questionnaire reflects the neuropsychiatric signs of biomarker-confirmed Alzheimer's disease in DS (DS-AD) remains unknown. To address this issue, we compared the plasma phosphorylated tau (P181tau: p-tau) level of a representative AD biomarker with the total score and each sub-score of the DSQIID.

Respiratory-gated proton beam therapy for intrahepatic cholangiocarcinoma without fiducial markers.

Background: Intrahepatic cholangiocarcinoma (ICC) is a challenging primary liver cancer with a poor prognosis, especially in unresectable cases. Traditional palliative irradiation is limited in reducing liver doses. This study aimed to evaluate the efficacy and toxicity of respiratory-gated proton beam therapy without fiducial markers for intrahepatic cholangiocarcinoma.

Plasma biomarkers of neurodegeneration in patients and high risk subjects with Lewy body disease.

Comorbid Alzheimer's disease (AD) neuropathology is common in Lewy body disease (LBD); however, AD comorbidity in the prodromal phase of LBD remains unclear. This study investigated AD comorbidity in the prodromal and symptomatic phases of LBD by analyzing plasma biomarkers in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and individuals at risk of LBD (NaT-PROBE cohort). Patients with PD (PD group, n = 84) and DLB (DLB group, n = 16) and individuals with LBD with ≥ 2 (high-risk group, n = 82) and without (low-risk group, n = 37) prodromal symptoms were enrolled.

Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry.

Background And Purpose: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy.

Materials And Methods: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy.

In Vivo Assessment of Astrocyte Reactivity in Patients with Progressive Supranuclear Palsy.

Objective: Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity.

Plasma biomarkers for predicting the development of dementia in a community-dwelling older Japanese population.

Aim: To assess the association between plasma amyloid β (Aβ) 42/40, phosphorylated tau (p-τ)181, glial fibrillary acidic protein (GFAP), or neurofilament light chain (NfL) and the risk of dementia and to determine whether these plasma biomarkers could improve the ability to predict incident dementia in a general older population.

Methods: A total of 1346 Japanese community-dwelling individuals aged ≥65 years without dementia were followed prospectively for 5.0 years.

Validation of a newly developed immunoassay for TDP-43 in human plasma.

The level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which involves the aggregation and deposition of TDP-43 in the nervous system. However, at present, no reliable immunoassay can precisely quantify TDP-43 in human plasma and detect the difference in plasma TDP-43 levels between patients with ALS and controls. We recently developed a novel ultrasensitive immunoassay to quantify TDP-43 in human plasma, and in this study, we analytically validated this assay for application as a diagnostic biomarker for TDP-43 proteinopathies.

Investigating neural dysfunction with abnormal protein deposition in Alzheimer's disease through magnetic resonance spectroscopic imaging, plasma biomarkers, and positron emission tomography.

In Alzheimer's disease (AD), aggregated abnormal proteins induce neuronal dysfunction. Despite the evidence supporting the association between tau proteins and brain atrophy, further studies are needed to explore their link to neuronal dysfunction in the human brain. To clarify the relationship between neuronal dysfunction and abnormal proteins in AD-affected brains, we conducted magnetic resonance spectroscopic imaging (MRSI) and assessed the neurofilament light chain plasma levels (NfL).

Altered Brain Energy Metabolism Related to Astrocytes in Alzheimer's Disease.

Objective: Increasing evidence suggests that reactive astrocytes are associated with Alzheimer's disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to altered brain energy metabolism.

Enzymatic properties and clinical associations of serum alpha-galactosidase A in Parkinson's disease.

Objective: Recent studies have revealed an association between Parkinson's disease (PD) and Fabry disease, a lysosomal storage disorder; however, the underlying mechanisms remain to be elucidated. This study aimed to investigate the enzymatic properties of serum alpha-galactosidase A (GLA) and compared them with the clinical parameters of PD.

Methods: The study participants consisted of 66 sporadic PD patients and 52 controls.

Clinical results of proton beam radiotherapy for inoperable stage III non-small cell lung cancer: a Japanese national registry study.

This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80 years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC.

Effectiveness of CT-image guidance in proton therapy for liver cancer and the importance of daily dose monitoring for tumors and organs at risk.

Background: It is important to have precise image guidance throughout proton therapy in order to take advantage of the therapy's physical selectivity.

Purpose: We evaluated the effectiveness of computed tomography (CT)-image guidance in proton therapy for patients with hepatocellular carcinoma (HCC) by assessing daily proton dose distributions. The importance of daily CT image-guided registration and daily proton dose monitoring for tumors and organs at risk (OARs) was investigated.

Comprehensive analysis of Japanese nationwide cohort data of particle beam therapy for pulmonary, liver and lymph node oligometastases: particle beam therapy versus high-precision X-ray radiotherapy.

Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e.

Evaluation of Exposure Doses of Elective Nodal Irradiation in Chemoradiotherapy for Advanced Esophageal Cancer.

We evaluated elective nodal irradiation (ENI) doses during radical chemoradiotherapy (CRT) for esophageal cancer (EC). A total of 79 patients (65 men and 14 women) aged 52-80 years with T1-3, N0-3, and M0 (including M1ly) who underwent CRT for EC during November 2012-September 2019 were eligible for this retrospective analysis. Patients were divided into two groups: the high-dose group (HG), including 38 patients who received ≥40 Gy as ENI; and the low-dose group (LG), including 41 patients who received <40 Gy.

Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers.

We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan-Meier method. Toxicity was graded per CTCAE v5.

Soluble TREM2 and Alzheimer-related biomarker trajectories in the blood of patients with diabetes based on their cognitive status.

Aim: We aimed to elucidate the dynamics of blood biomarkers according to the severity of cognitive impairment in patients with type 2 diabetes mellitus (DM) and to identify useful biomarkers for diabetes-related dementia.

Methods: This was a cross-sectional, nested case-control study of 121 Japanese DM and non-DM patients with different levels of cognitive functioning. We evaluated participants' cognitive functions, blood biomarkers related to Alzheimer's disease, and soluble triggering receptors expressed on myeloid cells 2 (sTREM2).

Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer.

Background: This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC).

Methods: The major inclusion criteria were clinical stage III NSCLC, age 20-74 years, and Eastern Cooperative Oncology Group performance status 0-1. Patients were treated with either cisplatin + S-1 (CS; four cycles every 4 weeks) or carboplatin + paclitaxel (CP; administered weekly with thoracic radiotherapy [RT], plus two consolidation cycles) concurrently with IMRT (60 Gy in 30 fractions).

Serum asymmetric dimethylarginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis.

Background And Purpose: The aim was to investigate the association between serum asymmetric dimethylarginine (ADMA) levels and the progression and prognosis of amyotrophic lateral sclerosis (ALS), and to compare cerebrospinal fluid (CSF) and serum ADMA levels with other biomarkers of ALS.

Methods: Serum ADMA levels of sporadic ALS patients (n = 68), disease control patients (n = 54) and healthy controls (n = 20) were measured using liquid chromatography tandem mass spectrometry. Correlations of the ADMA level and other markers (nitric oxide and neurofilament light chain levels) were analyzed.