David E. Kleiner
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View article: A rebrand for proteasome inhibition in solid tumors via continuous hepatic artery infusion
A rebrand for proteasome inhibition in solid tumors via continuous hepatic artery infusion Open
Targeting tumors with proteosome inhibitors has demonstrated antitumor activity and has been successfully translated to the clinic for patients with multiple myeloma. However, in patients with solid tumors, treatment with proteosome inhibi…
View article: T cell exhaustion in focus: single-cell mapping of CD8+ T cell dynamics in mucosal chronic graft-versus-host disease 3680
T cell exhaustion in focus: single-cell mapping of CD8+ T cell dynamics in mucosal chronic graft-versus-host disease 3680 Open
Description Chronic graft-versus-host disease (cGVHD) is an alloimmune disease that can follow non-self hematopoietic stem cell transplantation, driven by dysregulated T cell and other immune responses. Detailed analysis of naïve and memor…
View article: Translational framework linking perfluoroheptanoic acid (PFHpA) exposure to metabolic dysfunction associated steatotic liver disease in adolescents
Translational framework linking perfluoroheptanoic acid (PFHpA) exposure to metabolic dysfunction associated steatotic liver disease in adolescents Open
This study offers evidence implicating PFHpA, a short-chain unregulated PFAS congener, in MASLD development in adolescents, and highlights the critical role of protein dysregulation in disease pathogenesis. The molecular mechanisms identif…
View article: A simple circuit to sustain intact tumor microenvironments for complex drug interrogations
A simple circuit to sustain intact tumor microenvironments for complex drug interrogations Open
SUMMARY Deep learning and large language models can integrate complex datasets to uncover biological insights that are often undetectable through conventional analyses. With application to translational cancer research, these computational…
View article: Quantitative Assessment of Retention Mechanisms of Nucleosides on a Bare Silica Stationary Phase in Hydrophilic Interaction Liquid Chromatography (HILIC)
Quantitative Assessment of Retention Mechanisms of Nucleosides on a Bare Silica Stationary Phase in Hydrophilic Interaction Liquid Chromatography (HILIC) Open
Nucleosides are of significant interest to biomedical and pharmaceutical research and have been successfully separated in hydrophilic interaction liquid chromatography (HILIC). However, there have been few studies focusing on the retention…
View article: GZMK+CD8+ T cells target a specific acinar cell type in Sjögren's disease
GZMK+CD8+ T cells target a specific acinar cell type in Sjögren's disease Open
Using single-cell and spatial transcriptomics and proteomics, this study identifies a selective loss of PRR4⁺CST3⁺WFDC2⁻ seromucous acinar cells and a rise in GZMK⁺CD8⁺ T cells in Sjögren's disease, revealing distinct immune-mediated epith…
View article: Exhausted-like effector CD8 T cells mediate immune-stromal interactions at mucosal Chronic Graft-versus-Host Disease onset
Exhausted-like effector CD8 T cells mediate immune-stromal interactions at mucosal Chronic Graft-versus-Host Disease onset Open
Chronic graft-versus-host disease (cGVHD) frequently follows allogeneic hematopoietic stem cell transplantation and impacts the mucosa. This atlas study highlights the role of exhausted-like effector CD8 + T cells (T EXEF ) in oral mucosal…
View article: Associations of gender and a proxy of female menopausal status with histological features of drug‐induced liver injury
Associations of gender and a proxy of female menopausal status with histological features of drug‐induced liver injury Open
BACKGROUND & AIM: Gender and menopause may contribute to type and severity of drug-induced liver injury (DILI) by influencing host responses to injury. The aim of this study was to assess the associations of gender and female age 50 [a pro…
View article: Cardiopulmonary changes and its association with clinical features in noncirrhotic portal hypertension
Cardiopulmonary changes and its association with clinical features in noncirrhotic portal hypertension Open
BACKGROUND Cardiopulmonary changes in noncirrhotic portal hypertension (NCPH) are poorly understood. AIM To investigate cardiopulmonary changes using transthoracic echocardiography (TTE) in NCPH and their correlation with clinical features…
View article: A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework
A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework Open
Background: There is a substantial heritable component to metabolic dysfunction–associated steatotic liver disease (MASLD), and several genetic variants that promote MASLD development or associate with its severity have been reported. Thes…
View article: Clearance of Hepatitis C Viremia During Direct‐Acting Antiviral Therapy Leads to Rapid Changes in Lipid and Lipoprotein Metabolism
Clearance of Hepatitis C Viremia During Direct‐Acting Antiviral Therapy Leads to Rapid Changes in Lipid and Lipoprotein Metabolism Open
Background and Aims Chronic hepatitis C virus (HCV) infection is associated with hypolipidemia. HCV eradication may, therefore, result in hyperlipidemia and increase cardiovascular disease (CVD) risk. We investigated the impact of HCV erad…
View article: Preserved CD8+ T Cells, Severe Viral Infections, Profound Immune Dysregulation, and Variable Expressivity in a Kindred with Novel, Homozygous Pathogenic ZAP70 Splice-Site Variants
Preserved CD8+ T Cells, Severe Viral Infections, Profound Immune Dysregulation, and Variable Expressivity in a Kindred with Novel, Homozygous Pathogenic ZAP70 Splice-Site Variants Open
Few studies have assessed hypomorphic variants in ZAP70, leading to profound, late-onset combined immunodeficiency. A previously healthy 21-year-old man presented with primary EBV B cell lymphoproliferative disease (LPD). He developed hemo…
View article: Clinical associations of portal-based disease in MASLD: proposal of a new histological scoring system
Clinical associations of portal-based disease in MASLD: proposal of a new histological scoring system Open
Portal inflammation (PI) and ductular reaction (DR) in metabolic dysfunction-associated steatotic liver disease (MASLD) have shown associations with disease severity. We developed a histologic categorization of these features to correlate …
View article: ERAP-1 and ERAP-2 Variants in Liver Injury After COVID-19 mRNA Vaccination: A US Multicenter Study
ERAP-1 and ERAP-2 Variants in Liver Injury After COVID-19 mRNA Vaccination: A US Multicenter Study Open
INTRODUCTION: The aim of this study is to describe the presenting features, genetic factors, and outcomes of 23 adults who developed liver injury after coronavirus disease 2019 (COVID-19) mRNA vaccination. METHODS: Patients with suspected …
View article: Differential Intrahepatic Integrated HBV DNA Patterns Between HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B
Differential Intrahepatic Integrated HBV DNA Patterns Between HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B Open
Background HBsAg can be derived from intrahepatic cccDNA and integrated HBV DNA (iDNA). We examined the iDNA from liver tissues of 24 HBeAg(+) and 32 HBeAg(−) treatment-naive CHB participants. Methods Liver tissues were obtained from the N…
View article: Multiomics analysis of immune correlatives in hepatocellular carcinoma patients treated with tremelimumab plus durvalumab
Multiomics analysis of immune correlatives in hepatocellular carcinoma patients treated with tremelimumab plus durvalumab Open
Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. The combination of tremelimumab and durvalumab is now a standard treatment option for advanced HCC. Objective To study immune responses in HCC patien…
View article: Liver Injury due to Intravenous Methylprednisolone in the Drug‐Induced Liver Injury Network
Liver Injury due to Intravenous Methylprednisolone in the Drug‐Induced Liver Injury Network Open
Background and Aims Short courses of intravenous (iv) methylprednisolone (MP) can cause drug induced liver injury (DILI). The aim of this study was to assess the clinical features and HLA associations of MP‐related DILI enrolled in the US …
View article: Autoimmune‐Like Hepatitis Following Hepatic Graft‐Versus‐Host Disease in an Allogenic Hematopoietic Cell Transplant Recipient
Autoimmune‐Like Hepatitis Following Hepatic Graft‐Versus‐Host Disease in an Allogenic Hematopoietic Cell Transplant Recipient Open
One of the major complications following hematopoietic cell transplantation (HCT) is the occurrence of graft‐versus‐host disease (GVHD). The liver is a target organ in both acute and chronic GVHD. Histologically, there are two distinct for…
View article: SARS-CoV-2 infection of salivary glands compromises the production of a secreted antifungal peptide with potential implications for development of oral candidiasis
SARS-CoV-2 infection of salivary glands compromises the production of a secreted antifungal peptide with potential implications for development of oral candidiasis Open
Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands wit…
View article: Role of liver biopsy in the management of idiosyncratic <scp>DILI</scp>
Role of liver biopsy in the management of idiosyncratic <span>DILI</span> Open
Drug‐induced liver injury (DILI) presents unique challenges in clinical practice. While some types of DILI are mild and resolve quickly after removing the drug, other situations are more complex, with competing aetiologies or underlying li…