Biology subjects

Zhuo, J.

Publications and source records attributed to Zhuo, J..

3 recordsLinked to original sources

bioRxiv2021

BAI-Net: Individualized Human Cerebral Cartography using Graph Convolutional Network

Brain atlas is an important tool in the diagnosis and treatment of neurological disorders. However, due to large variations in the organizational principles of individual brains, many challenges remain in clinical applications. Brain atlas individualization network (BAI-Net) is an algorithm that subdivides individual cerebral cortex into segregated areas using brain morphology and connectomes. BAI-Net integrates topological priors derived from a group atlas, adjusts the areal probability using the connectivity context derived from diffusion tractography, and provides reliable and explainable individualized brain parcels across multiple sessions and scanners. We demonstrate that BAI-Net outperforms the conventional iterative clustering approach by capturing significantly heritable topographic variations in individualized cartographies. The topographic variability of BAI-Net cartographies shows strong associations with individual variability in brain morphology, connectivity fingerprints and cognitive behaviors. This study provides a new framework for individualized brain cartography and paves the way of atlas-based precision medicine in clinical practice.

neuroscience↗

bioRxiv2021

CUB domain containing protein 1 (CDPC1) is a target for radioligand therapy in castration resistant prostate cancer

PurposeRadioligand therapy (RLT) is relatively unexplored in metastatic castration resistant prostate cancer (mCRPC), with much of the focus having been on bone seeking radionuclides and PSMA-directed RLT. Herein, we evaluated if CUB domain containing protein 1 (CDCP1) can be exploited to treat mCRPC with RLT, particularly for subsets like small cell neuroendocrine prostate cancer (SCNC) that would not be expected to respond to current options. Experimental DesignCDCP1 mRNA levels were evaluated in the RNA-seq data from 119 recent mCRPC biopsies. Protein expression was assessed in twelve SCNC and adenocarcinoma patient derived xenografts. Saturation binding assays were performed with 4A06, a recombinant human antibody that targets the CDCP1 ectodomain. The feasibility of imaging and treating mCRPC in vivo was tested with 89Zr-4A06 and 177Lu-4A06. ResultsCDCP1 mRNA expression was observed in over 90% of mCRPC biopsies, including SCNC and in adenocarcinoma with low FOLH1 (PSMA) levels. A modest anticorrelation was observed between CDCP1 and PTEN. Overall survival was not significantly different based on CDCP1 mRNA levels, regardless of PTEN status. Full length and/or cleaved CDCP1 was expressed in ten of twelve PDX samples. Bmax values of ~22,000 and ~6,200 fmol/mg were calculated for two human prostate cancer cell lines. Five prostate cancer models were readily detected in vivo with 89Zr-4A06. 177Lu-4A06 significantly suppressed the growth of DU145 tumors compared to control. ConclusionsThe antitumor data and the overexpression of CDCP1 reported herein provide the first evidence promoting CDCP1 directed RLT as a treatment strategy for mCRPC. Statement of Translational RelevanceNew targets for RLT are needed to address the subset of mCRPC that cannot be treated with bone seeking radionuclides or PSMA directed RLT. We report herein the first data credentialing CDCP1 as a target for mCRPC, in both adenocarcinoma and neuroendocrine subtypes. Combined with low expression in normal human tissues, these data provide a compelling scientific rationale for testing CDCP1 directed RLT clinically in mCRPC patients alone or in combination with other systemic therapies.

cancer biology↗

bioRxiv2020

Clinical and biomarker changes in sporadic Alzheimer's disease: Amyloid-β not useful marker for disease onset or progression

IMPORTANCEThe dynamic changes of biomarkers and clinical profiles in sporadic Alzheimers disease (SAD) are poorly understood. OBJECTIVETo evaluate the impact of amyloid-{beta} (A{beta}) biomarkers on SAD by measuring the dynamic changes in biomarkers and clinical profiles in the progression of SAD. DESIGN AND SETTINGThis retrospective and longitudinal study analyzed clinical and biomarker data from 665 participants (mean follow-up 4.90 {+/-} 2.83 years) from a subset of the AD Neuroimaging Initiative (ADNI) participants collected from August 2005 to December 2018. By aligning the timing of the changes in the various biomarkers with the stable normal cognition (CN) baseline and mild cognitive impairment (MCI) or AD onset timepoints, we combined data from the stable CN, CN conversion to MCI (CN2MCI), and MCI conversion to AD (MCI2AD) groups to identify the trajectories associated with the progression of AD. PARTICIPANTSThe participants were 294 CN, 69 CN2MCI, 300 MCI2AD, and 24 who converted from CN to MCI to AD (CN2MCI2AD) (of whom 22 were also included in the CN2MCI). EXPOSURESAmyloid-{beta} measured by florbetapir positron emission tomography (PET) or cerebrospinal fluid assay of amyloid-{beta} (CSF A{beta}42). MAIN OUTCOMES AND MEASURESThe measures included the 13-item cognitive subscale of the AD Assessment Scale (ADAS13, as a clinical measure), hippocampal volume, and the fluorodeoxyglucose (FDG) PET standardized uptake value ratio (SUVR). RESULTSThe CN, CN2MCI, and MCI2AD subgroups median (interquartile range [IQR]) annual changes in ADAS13 were (0.388 [-0.278, 0.818], 1.000 [0.239, 2.330], and 3.388 [1.750, 6.169]). The annual changes in hippocampal volume for each group were (-0.005 %ICV [-0.011, -0.001], -0.006 %ICV [-0.012, -0.002], and -0.014 %ICV [-0.021, -0.009]). The annual changes in FDG PET SUVR for each group were (-0.011 [-0.030, 0.010], -0.027 [-0.056, -0.012], and -0.039 [-0.063, 0.014]). Changes in the amyloid biomarkers were inconsistent with clinical profile changes. The annual changes in CSF A{beta}42 for each group were (-1.500 pg/ml [-6.000, 4.000], -2.200 [-5.667, 4.000], and -2.000 [-7.000, 2.650]) and in A{beta} PET SUVR for each group were (0.004 [-0.002, 0.012], 0.004 [-0.001,0.011], and 0.005 [-0.006, 0.014]). During the stable CN and CN2MCI stages, subjects with elevated and those with normal amyloid showed no significant differences (likelihood ratio test, p < .01) in clinical measures, hippocampal volume, or FDG. CONCLUSIONS AND RELEVANCEHippocampal volume and FDG associated with clinical profiles impairment in the SAD progression. A{beta} alone is not associated with clinical profiles, hippocampal volume, and FDG impairment in the preclinical stage of SAD. Key PointsQuestion: What is the role of amyloid-{beta} in dynamic changes in biomarkers and clinical profiles in the progression of sporadic Alzheimers disease? Findings: The changes of the hippocampal volume and FDG that were consistent with the changes of the clinical profiles showed a non-linear change in the initial stage and an accelerated non-linear change during MCI2AD, changes in amyloid biomarkers were inconsistent with the clinical profile. Cognitively normal people with elevated or normal amyloid showed no significant differences in clinical measures, hippocampal volume, or FDG. Meaning: Amyloid-{beta} alone may not be used as the central index for defining the preclinical stage of SAD.

neuroscience↗