Publications by authors named "D J Kim"

42,754 Publications

Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the United States.

Hepatology 2021 Jul 26. Epub 2021 Jul 26.

Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston.

Background & Aims: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the US. We evaluated the impact of the pandemic on temporal trends for LT including ALD.

Approach & Results: Utilizing data from United Network for Organ Sharing, we analyzed waitlist outcomes in the US through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019 and February 29, 2020 were defined as the "pre-COVID" era and after April 1, 2020 were defined as the "COVID" era. Interrupted time-series analyses utilizing monthly count data from 2016-2020 were constructed to evaluate rate change for listing and LT prior to and during the COVID-19 pandemic. Rates for listings (P=0.19) and LT (P=0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P <0.001) and NASH (-13.18%; P <0.001). There was a significant increase in ALD listing (+7.26%; P <0.001) and LT (10.67%; P <0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcoholic hepatitis (+50%). ALD patients presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a MELD-Na ≥ 30.

Conclusions: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on healthcare resources.
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http://dx.doi.org/10.1002/hep.32067DOI Listing
July 2021

Unsupervised Learning of Reference Bony Shapes for Orthognathic Surgical Planning with a Surface Deformation Network.

Med Phys 2021 Jul 26. Epub 2021 Jul 26.

Department of Oral and Maxillofacial Surgery, Houston Methodist Hospital, Houston, TX, 77030, USA.

Purpose: To reduce the experience dependence during the orthognathic surgical planning that involves virtually simulating the corrective procedure for jaw deformities.

Methods: We introduce a geometric deep learning framework for generating reference facial bone shape models for objective guidance in surgical planning. First, we propose a surface deformation network to warp a patient's deformed bone to a set of normal bones for generating a dictionary of patient-specific normal bony shapes. Subsequently, sparse representation learning is employed to estimate a reference shape model based on the dictionary.

Results: We evaluated our method on a clinical dataset containing 24 patients, and compared it with a state-of-the-art method that relies on landmark-based sparse representation. Our method yields significantly higher accuracy than the competing method for estimating normal jaws, and maintains the midfaces of patients' facial bones as well as the conventional way.

Conclusions: Experimental results indicate that our method generates accurate shape models that meet clinical standards.
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http://dx.doi.org/10.1002/mp.15126DOI Listing
July 2021

Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer's Disease.

J Med Chem 2021 Jul 26. Epub 2021 Jul 26.

Department of Pharmaceutical Sciences, University of Kentucky, 789 South Limestone, Lexington, Kentucky 40536-0596, United States.

Previously, we reported that immunoproteasome (iP)-targeting linear peptide epoxyketones improve cognitive function in mouse models of Alzheimer's disease (AD) in a manner independent of amyloid β. However, these compounds' clinical prospect for AD is limited due to potential issues, such as poor brain penetration and metabolic instability. Here, we report the development of iP-selective macrocyclic peptide epoxyketones prepared by a ring-closing metathesis reaction between two terminal alkenes attached at the P2 and P3/P4 positions of linear counterparts. We show that a lead macrocyclic compound DB-60 () effectively inhibits the catalytic activity of iP in ABCB1-overexpressing cells (IC: 105 nM) and has metabolic stability superior to its linear counterpart. DB-60 () also lowered the serum levels of IL-1α and ameliorated cognitive deficits in Tg2576 mice. The results collectively suggest that macrocyclic peptide epoxyketones have improved CNS drug properties than their linear counterparts and offer promising potential as an AD drug candidate.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00291DOI Listing
July 2021

Functional Magnetic Resonance Imaging Signal Variability Is Associated With Neuromodulation in Fibromyalgia.

Neuromodulation 2021 Jul 26. Epub 2021 Jul 26.

Headache and Orofacial Pain Effort (H.O.P.E.), Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.

Objectives: Although primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and efficiency and if this change is associated with pain improvement.

Materials And Methods: In a within-subjects cross-over design, 12 female FM patients underwent sham and active tDCS on five consecutive days, respectively. Each session was performed with an anode placed on the left M1 and a cathode on the contralateral supraorbital region. The subjects also participated in resting-state functional magnetic resonance imaging (fMRI) at baseline and after sham and active tDCS. We compared the BOLD signal variability (SD ), defined as the standard deviation of the BOLD time-series, between the tDCS conditions. Baseline SD was compared to 15 healthy female controls.

Results: At baseline, FM patients showed reduced SD in the ventromedial prefrontal cortex (vmPFC), lateral PFC, and anterior insula and increased SD in the posterior insula compared to healthy controls. After active tDCS, compared to sham, we found an increased SD in the left rostral anterior cingulate cortex (rACC), lateral PFC, and thalamus. After sham tDCS, compared to baseline, we found a decreased SD in the dorsomedial PFC and posterior cingulate cortex/precuneus. Interestingly, after active tDCS compared to sham, pain reduction was correlated with an increased SD in the rACC/vmPFC but with a decreased SD in the posterior insula.

Conclusion: Our findings suggest that M1-tDCS might revert temporal variability of fMRI signals in the rACC/vmPFC and posterior insula linked to FM pain. Changes in neural variability would be part of the mechanisms underlying repetitive M1-tDCS analgesia in FM.
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http://dx.doi.org/10.1111/ner.13512DOI Listing
July 2021

Neuropathology of Perry Syndrome: Evidence of Medullary and Hypothalamic Involvement.

Mov Disord Clin Pract 2021 Jul 27;8(5):713-716. Epub 2021 May 27.

Department of Clinical Neurological Sciences Western University London Ontario Canada.

Background: Perry syndrome is a rare genetic parkinsonian disorder with TAR DNA binding protein 43 (TDP-43) pathology clinically presenting with parkinsonism, neuropsychiatric features, weight loss, and central hypoventilation. As respiratory complications are often the cause of death, studies likely show the early stage of the neurodegenerative process. Because of the rarity of this condition, few studies exist, and each case provides insight into pathological findings in this neurodegenerative condition.

Objective: To study the clinical and pathological correlations of an autopsy case of Perry syndrome.

Methods: The patient was a woman in her 50s with Perry syndrome and a gene mutation. Between October 2016 and July 2019, she underwent postmortem and pathological examination at University Hospital in London, Ontario, Canada. Data were obtained through clinical pathological examination.

Results: Microscopy showed significant neuronal loss with pigmentary incontinence and gliosis in the substantia nigra. There was no atrophy elsewhere, including the frontal and cingulate cortex. Intraneuronal cytoplasmic TDP-43 inclusions and neurites were noticed in a moderate number in the substantia nigra and midbrain and were sparsely noticed in the basal ganglia, thalamus, thoracic motor neuron, posterior nucleus of the hypothalamus, and rostral ventral medulla. β-Amyloid, Lewy body, and tau pathologies were absent. Rare axonal swelling was identified at the rostral ventrolateral medulla.

Conclusions And Relevance: This study confirms that Perry syndrome is characterized by TDP-43 pathology with absent Lewy bodies or tau pathology. These findings support the hypothesis of dysfunctional neurons in the medulla and hypothalamus, which may respectively correlate to the clinical symptoms of hypoventilation and weight loss in Perry syndrome.
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http://dx.doi.org/10.1002/mdc3.13235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287159PMC
July 2021
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