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Full-Text Articles in Diseases

Effects Of Chronic Cirrhosis Induced By Intraperitoneal Thioacetamide Injection On The Protein Content And Michaelis–Menten Kinetics Of Cytochrome P450 Enzymes In The Rat Liver Microsomes, Devaraj Venkatapura Chandrashekar, Barent N. Dubois, Mamunur Rashid, Reza Mehvar Nov 2022

Effects Of Chronic Cirrhosis Induced By Intraperitoneal Thioacetamide Injection On The Protein Content And Michaelis–Menten Kinetics Of Cytochrome P450 Enzymes In The Rat Liver Microsomes, Devaraj Venkatapura Chandrashekar, Barent N. Dubois, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by …


Sars-Cov-2 Incubation Period According To Vaccination Status During The Fifth Covid-19 Wave In A Tertiary-Care Center In Spain: A Cohort Study, Jordi Cortés Martínez, Daewoo Pak, Gabriela Abelenda-Alonso, Klaus Langohr, Jing Ning, Alexander Rombauts, Mireia Colom, Yu Shen, Guadalupe Gómez Melis Nov 2022

Sars-Cov-2 Incubation Period According To Vaccination Status During The Fifth Covid-19 Wave In A Tertiary-Care Center In Spain: A Cohort Study, Jordi Cortés Martínez, Daewoo Pak, Gabriela Abelenda-Alonso, Klaus Langohr, Jing Ning, Alexander Rombauts, Mireia Colom, Yu Shen, Guadalupe Gómez Melis

Faculty, Staff and Student Publications

Background: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period.

Methods: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The …


Radiation Therapy Induces Immunosenescence Mediated By P90rsk, Masaki Imanishi, Haizi Cheng, Sivareddy Kotla, Anita Deswal, Nhat-Tu Le, Eduardo Chini, Kyung Ae Ko, Venkata S K Samanthapudi, Ling-Ling Lee, Joerg Herrmann, Xiaolei Xu, Cielito Reyes-Gibby, Sai-Ching J Yeung, Keri L Schadler, Syed Wamique Yusuf, Zhongxing Liao, Roza Nurieva, El-Ad David Amir, Jared K Burks, Nicolas L Palaskas, John P Cooke, Steven H Lin, Michihiro Kobayashi, Momoko Yoshimoto, Jun-Ichi Abe Nov 2022

Radiation Therapy Induces Immunosenescence Mediated By P90rsk, Masaki Imanishi, Haizi Cheng, Sivareddy Kotla, Anita Deswal, Nhat-Tu Le, Eduardo Chini, Kyung Ae Ko, Venkata S K Samanthapudi, Ling-Ling Lee, Joerg Herrmann, Xiaolei Xu, Cielito Reyes-Gibby, Sai-Ching J Yeung, Keri L Schadler, Syed Wamique Yusuf, Zhongxing Liao, Roza Nurieva, El-Ad David Amir, Jared K Burks, Nicolas L Palaskas, John P Cooke, Steven H Lin, Michihiro Kobayashi, Momoko Yoshimoto, Jun-Ichi Abe

Faculty, Staff and Student Publications

Radiation therapy (RT) to the chest increases the patients’ risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. …


Dll3 As An Emerging Target For The Treatment Of Neuroendocrine Neoplasms, James Yao, Emily Bergsland, Rahul Aggarwal, Ana Aparicio, Himisha Beltran, Judy S Crabtree, Christine L Hann, Toni Ibrahim, Lauren A Byers, Hironobu Sasano, John Umejiego, Marianne Pavel Nov 2022

Dll3 As An Emerging Target For The Treatment Of Neuroendocrine Neoplasms, James Yao, Emily Bergsland, Rahul Aggarwal, Ana Aparicio, Himisha Beltran, Judy S Crabtree, Christine L Hann, Toni Ibrahim, Lauren A Byers, Hironobu Sasano, John Umejiego, Marianne Pavel

Faculty, Staff and Student Publications

INTRODUCTION: Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis.

METHODS: This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the …


Targeting The Eif2ak1 Signaling Pathway Rescues Red Blood Cell Production In Sf3b1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts, Vera Adema, Feiyang Ma, Rashmi Kanagal-Shamanna, Natthakan Thongon, Guillermo Montalban-Bravo, Hui Yang, Scott A Peslak, Feng Wang, Pamela Acha, Francesc Sole, Pamela Lockyer, Margherita Cassari, Jaroslaw P Maciejewski, Valeria Visconte, Irene Gañán-Gómez, Yuanbin Song, Carlos Bueso-Ramos, Matteo Pellegrini, Tuyet M Tan, Rafael Bejar, Jennifer S Carew, Stephanie Halene, Valeria Santini, Gheath Al-Atrash, Karen Clise-Dwyer, Guillermo Garcia-Manero, Gerd A Blobel, Simona Colla Nov 2022

Targeting The Eif2ak1 Signaling Pathway Rescues Red Blood Cell Production In Sf3b1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts, Vera Adema, Feiyang Ma, Rashmi Kanagal-Shamanna, Natthakan Thongon, Guillermo Montalban-Bravo, Hui Yang, Scott A Peslak, Feng Wang, Pamela Acha, Francesc Sole, Pamela Lockyer, Margherita Cassari, Jaroslaw P Maciejewski, Valeria Visconte, Irene Gañán-Gómez, Yuanbin Song, Carlos Bueso-Ramos, Matteo Pellegrini, Tuyet M Tan, Rafael Bejar, Jennifer S Carew, Stephanie Halene, Valeria Santini, Gheath Al-Atrash, Karen Clise-Dwyer, Guillermo Garcia-Manero, Gerd A Blobel, Simona Colla

Faculty, Staff and Student Publications

SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks of a specific MDS subtype, MDS with ringed sideroblasts (MDS-RS), which is characterized by the accumulation of erythroid precursors in the bone marrow and primarily affects the elderly population. Here, using single-cell technologies and functional validation studies of primary SF3B1-mutant MDS-RS samples, we show that SF3B1 mutations lead to the activation of the EIF2AK1 pathway in response to heme deficiency and that targeting this pathway rescues aberrant erythroid differentiation and enables the red blood cell maturation of MDS-RS erythroblasts. These data support the development of …


Tp53-Mutated Myelodysplastic Syndrome And Acute Myeloid Leukemia: Biology, Current Therapy, And Future Directions, Naval G Daver, Abhishek Maiti, Tapan M Kadia, Paresh Vyas, Ravindra Majeti, Andrew H Wei, Guillermo Garcia-Manero, Charles Craddock, David A Sallman, Hagop M Kantarjian Nov 2022

Tp53-Mutated Myelodysplastic Syndrome And Acute Myeloid Leukemia: Biology, Current Therapy, And Future Directions, Naval G Daver, Abhishek Maiti, Tapan M Kadia, Paresh Vyas, Ravindra Majeti, Andrew H Wei, Guillermo Garcia-Manero, Charles Craddock, David A Sallman, Hagop M Kantarjian

Faculty, Staff and Student Publications

UNLABELLED: TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) form a distinct group of myeloid disorders with dismal outcomes. TP53-mutated MDS and AML have lower response rates to either induction chemotherapy, hypomethylating agent-based regimens, or venetoclax-based therapies compared with non-TP53-mutated counterparts and a poor median overall survival of 5 to 10 months. Recent advances have identified novel pathogenic mechanisms in TP53-mutated myeloid malignancies, which have the potential to improve treatment strategies in this distinct clinical subgroup. In this review, we discuss recent insights into the biology of TP53-mutated MDS/AML, current treatments, and emerging therapies, including immunotherapeutic and nonimmune-based approaches …


Graphic Novel, Maya Sanchez Nov 2022

Graphic Novel, Maya Sanchez

Human Diseases Graphic Novels

No abstract provided.


The Immune System: Arthritis, Melanie Cuenca '23, Rylie Bozarth '23 Nov 2022

The Immune System: Arthritis, Melanie Cuenca '23, Rylie Bozarth '23

Human Diseases Graphic Novels

No abstract provided.


The Skeletal System – Osteoporosis, Melanie Cuenca '23, Rylie Bozarth '23 Nov 2022

The Skeletal System – Osteoporosis, Melanie Cuenca '23, Rylie Bozarth '23

Human Diseases Graphic Novels

No abstract provided.


Asthma / Pneunomia / Cystic Acne / Eczema, Gabi Pride '24, Clarissa Gonzalez '24 Nov 2022

Asthma / Pneunomia / Cystic Acne / Eczema, Gabi Pride '24, Clarissa Gonzalez '24

Human Diseases Graphic Novels

No abstract provided.


Asthma, Sophia Syed '23, Grace Daum '23, Shanan Riley '23, Liz Carlson '23 Nov 2022

Asthma, Sophia Syed '23, Grace Daum '23, Shanan Riley '23, Liz Carlson '23

Human Diseases Graphic Novels

No abstract provided.


Bell's Palsy, Munachiso Onwuameze '24, Destiny Grant '23, Kosi Okeke '24 Nov 2022

Bell's Palsy, Munachiso Onwuameze '24, Destiny Grant '23, Kosi Okeke '24

Human Diseases Graphic Novels

No abstract provided.


Chicken Pox, Ela Gadi '23, Braeden Cullen '23, Madhav Hota '24, Alan James Anterola, Kenith Taukolo '23 Nov 2022

Chicken Pox, Ela Gadi '23, Braeden Cullen '23, Madhav Hota '24, Alan James Anterola, Kenith Taukolo '23

Human Diseases Graphic Novels

No abstract provided.


Diabetes, Alan James Anterola, Kenith Taukolo '23, Braeden Cullen '23, Madhav Hota '24, Ela Gadi '23 Nov 2022

Diabetes, Alan James Anterola, Kenith Taukolo '23, Braeden Cullen '23, Madhav Hota '24, Ela Gadi '23

Human Diseases Graphic Novels

No abstract provided.


Reproductive System, Elle Brittin '23, Gwen Olney '24, Lily Powell '23 Nov 2022

Reproductive System, Elle Brittin '23, Gwen Olney '24, Lily Powell '23

Human Diseases Graphic Novels

No abstract provided.


Pneumonia, Munachiso Onwuameze '24, Kosi Okeke '24, Destiny Grant '23 Nov 2022

Pneumonia, Munachiso Onwuameze '24, Kosi Okeke '24, Destiny Grant '23

Human Diseases Graphic Novels

No abstract provided.


The Digestive System, Elle Brittin '23, Gwen Olney '24 Nov 2022

The Digestive System, Elle Brittin '23, Gwen Olney '24

Human Diseases Graphic Novels

No abstract provided.


Peptic Ulcer, Shanan Riley '23, Grace Daum '23, Sophia Syed '23, Elizabeth Carlson '23 Nov 2022

Peptic Ulcer, Shanan Riley '23, Grace Daum '23, Sophia Syed '23, Elizabeth Carlson '23

Human Diseases Graphic Novels

No abstract provided.


Hashimoto's Disease, Madilyn Bulfer, Yareli Marinez, Halimat Sanusi Nov 2022

Hashimoto's Disease, Madilyn Bulfer, Yareli Marinez, Halimat Sanusi

Human Diseases Graphic Novels

No abstract provided.


Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller Nov 2022

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8+ and CD4 …


Evaluation Of Wheat-Specific Peptide Targets For Use In The Development Of Elisa And Mass Spectrometry-Based Detection Methods, Jessica Humphrey Nov 2022

Evaluation Of Wheat-Specific Peptide Targets For Use In The Development Of Elisa And Mass Spectrometry-Based Detection Methods, Jessica Humphrey

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Individuals with IgE-mediated wheat allergy and celiac disease must avoid the consumption of wheat. Those with celiac disease must also avoid rye and barley in addition to wheat as these make up the gluten-containing grains. To ensure products are accurately labeled, ELISA methods may be used to monitor compliance with food allergen and gluten-free regulations. Currently, available ELISA methods for wheat detection utilize monoclonal antibodies that target peptides from the gluten fraction of proteins, and therefore, also detect rye and barley. Limitations such as differing antibody reactivity and unequal gluten content among wheat, rye, and barley have led to inconsistent …


Stroke Genetics Informs Drug Discovery And Risk Prediction Across Ancestries, Aniket Mishra, Rainer Malik, Tsuyoshi Hachiya, Tuuli Jürgenson, Shinichi Namba, Daniel C Posner, Frederick K Kamanu, Masaru Koido, Quentin Le Grand, Mingyang Shi, Yunye He, Marios K Georgakis, Ilana Caro, Kristi Krebs, Yi-Ching Liaw, Felix C Vaura, Kuang Lin, Bendik Slagsvold Winsvold, Vinodh Srinivasasainagendra, Livia Parodi, Hee-Joon Bae, Ganesh Chauhan, Michael R Chong, Liisa Tomppo, Rufus Akinyemi, Gennady V Roshchupkin, Naomi Habib, Yon Ho Jee, Jesper Qvist Thomassen, Vida Abedi, Jara Cárcel-Márquez, Marianne Nygaard, Hampton L Leonard, Chaojie Yang, Ekaterina Yonova-Doing, Maria J Knol, Adam J Lewis, Renae L Judy, Tetsuro Ago, Philippe Amouyel, Nicole D Armstrong, Mark K Bakker, Traci M Bartz, David A Bennett, Joshua C Bis, Constance Bordes, Sigrid Børte, Anael Cain, Paul M Ridker, Kelly Cho, Zhengming Chen, Carlos Cruchaga, John W Cole, Phil L De Jager, Rafael De Cid, Matthias Endres, Leslie E Ferreira, Mirjam I Geerlings, Natalie C Gasca, Vilmundur Gudnason, Jun Hata, Jing He, Alicia K Heath, Yuk-Lam Ho, Aki S Havulinna, Jemma C Hopewell, Hyacinth I Hyacinth, Michael Inouye, Mina A Jacob, Christina E Jeon, Christina Jern, Masahiro Kamouchi, Keith L Keene, Takanari Kitazono, Steven J Kittner, Takahiro Konuma, Amit Kumar, Paul Lacaze, Lenore J Launer, Keon-Joo Lee, Kaido Lepik, Jiang Li, Liming Li, Ani Manichaikul, Hugh S Markus, Nicholas A Marston, Thomas Meitinger, Braxton D Mitchell, Felipe A Montellano, Takayuki Morisaki, Thomas H Mosley, Mike A Nalls, Børge G Nordestgaard, Martin J O'Donnell, Yukinori Okada, N Charlotte Onland-Moret, Bruce Ovbiagele, Annette Peters, Bruce M Psaty, Stephen S Rich, Jonathan Rosand, Marc S Sabatine, Ralph L Sacco, Danish Saleheen, Else Charlotte Sandset, Veikko Salomaa, Muralidharan Sargurupremraj, Makoto Sasaki, Claudia L Satizabal, Carsten O Schmidt, Atsushi Shimizu, Nicholas L Smith, Kelly L Sloane, Yoichi Sutoh, Yan V Sun, Kozo Tanno, Steffen Tiedt, Turgut Tatlisumak, Nuria P Torres-Aguila, Hemant K Tiwari, David-Alexandre Trégouët, Stella Trompet, Anil Man Tuladhar, Anne Tybjærg-Hansen, Marion Van Vugt, Riina Vibo, Shefali S Verma, Kerri L Wiggins, Patrik Wennberg, Daniel Woo, Peter W F Wilson, Huichun Xu, Qiong Yang, Kyungheon Yoon, Compass Consortium, Invent Consortium, Dutch Parelsnoer Initiative (Psi) Cerebrovascular Disease Study Group, Estonian Biobank, Precise4q Consortium, Finngen Consortium, Ninds Stroke Genetics Network (Sign), Megastroke Consortium, Siren Consortium, China Kadoorie Biobank Collaborative Group, Va Million Veteran Program, International Stroke Genetics Consortium (Isgc), Biobank Japan, Charge Consortium, Gigastroke Consortium, Iona Y Millwood, Christian Gieger, Toshiharu Ninomiya, Hans J Grabe, J Wouter Jukema, Ina L Rissanen, Daniel Strbian, Young Jin Kim, Pei-Hsin Chen, Ernst Mayerhofer, Joanna M M Howson, Marguerite R Irvin, Hieab Adams, Sylvia Wassertheil-Smoller, Kaare Christensen, Mohammad A Ikram, Tatjana Rundek, Bradford B Worrall, G Mark Lathrop, Moeen Riaz, Eleanor M Simonsick, Janika Kõrv, Paulo H C França, Ramin Zand, Kameshwar Prasad, Ruth Frikke-Schmidt, Frank-Erik De Leeuw, Thomas Liman, Karl Georg Haeusler, Ynte M Ruigrok, Peter Ulrich Heuschmann, W T Longstreth, Keum Ji Jung, Lisa Bastarache, Guillaume Paré, Scott M Damrauer, Daniel I Chasman, Jerome I Rotter, Christopher D Anderson, John-Anker Zwart, Teemu J Niiranen, Myriam Fornage, Yung-Po Liaw, Sudha Seshadri, Israel Fernández-Cadenas, Robin G Walters, Christian T Ruff, Mayowa O Owolabi, Jennifer E Huffman, Lili Milani, Yoichiro Kamatani, Martin Dichgans, Stephanie Debette Nov 2022

Stroke Genetics Informs Drug Discovery And Risk Prediction Across Ancestries, Aniket Mishra, Rainer Malik, Tsuyoshi Hachiya, Tuuli Jürgenson, Shinichi Namba, Daniel C Posner, Frederick K Kamanu, Masaru Koido, Quentin Le Grand, Mingyang Shi, Yunye He, Marios K Georgakis, Ilana Caro, Kristi Krebs, Yi-Ching Liaw, Felix C Vaura, Kuang Lin, Bendik Slagsvold Winsvold, Vinodh Srinivasasainagendra, Livia Parodi, Hee-Joon Bae, Ganesh Chauhan, Michael R Chong, Liisa Tomppo, Rufus Akinyemi, Gennady V Roshchupkin, Naomi Habib, Yon Ho Jee, Jesper Qvist Thomassen, Vida Abedi, Jara Cárcel-Márquez, Marianne Nygaard, Hampton L Leonard, Chaojie Yang, Ekaterina Yonova-Doing, Maria J Knol, Adam J Lewis, Renae L Judy, Tetsuro Ago, Philippe Amouyel, Nicole D Armstrong, Mark K Bakker, Traci M Bartz, David A Bennett, Joshua C Bis, Constance Bordes, Sigrid Børte, Anael Cain, Paul M Ridker, Kelly Cho, Zhengming Chen, Carlos Cruchaga, John W Cole, Phil L De Jager, Rafael De Cid, Matthias Endres, Leslie E Ferreira, Mirjam I Geerlings, Natalie C Gasca, Vilmundur Gudnason, Jun Hata, Jing He, Alicia K Heath, Yuk-Lam Ho, Aki S Havulinna, Jemma C Hopewell, Hyacinth I Hyacinth, Michael Inouye, Mina A Jacob, Christina E Jeon, Christina Jern, Masahiro Kamouchi, Keith L Keene, Takanari Kitazono, Steven J Kittner, Takahiro Konuma, Amit Kumar, Paul Lacaze, Lenore J Launer, Keon-Joo Lee, Kaido Lepik, Jiang Li, Liming Li, Ani Manichaikul, Hugh S Markus, Nicholas A Marston, Thomas Meitinger, Braxton D Mitchell, Felipe A Montellano, Takayuki Morisaki, Thomas H Mosley, Mike A Nalls, Børge G Nordestgaard, Martin J O'Donnell, Yukinori Okada, N Charlotte Onland-Moret, Bruce Ovbiagele, Annette Peters, Bruce M Psaty, Stephen S Rich, Jonathan Rosand, Marc S Sabatine, Ralph L Sacco, Danish Saleheen, Else Charlotte Sandset, Veikko Salomaa, Muralidharan Sargurupremraj, Makoto Sasaki, Claudia L Satizabal, Carsten O Schmidt, Atsushi Shimizu, Nicholas L Smith, Kelly L Sloane, Yoichi Sutoh, Yan V Sun, Kozo Tanno, Steffen Tiedt, Turgut Tatlisumak, Nuria P Torres-Aguila, Hemant K Tiwari, David-Alexandre Trégouët, Stella Trompet, Anil Man Tuladhar, Anne Tybjærg-Hansen, Marion Van Vugt, Riina Vibo, Shefali S Verma, Kerri L Wiggins, Patrik Wennberg, Daniel Woo, Peter W F Wilson, Huichun Xu, Qiong Yang, Kyungheon Yoon, Compass Consortium, Invent Consortium, Dutch Parelsnoer Initiative (Psi) Cerebrovascular Disease Study Group, Estonian Biobank, Precise4q Consortium, Finngen Consortium, Ninds Stroke Genetics Network (Sign), Megastroke Consortium, Siren Consortium, China Kadoorie Biobank Collaborative Group, Va Million Veteran Program, International Stroke Genetics Consortium (Isgc), Biobank Japan, Charge Consortium, Gigastroke Consortium, Iona Y Millwood, Christian Gieger, Toshiharu Ninomiya, Hans J Grabe, J Wouter Jukema, Ina L Rissanen, Daniel Strbian, Young Jin Kim, Pei-Hsin Chen, Ernst Mayerhofer, Joanna M M Howson, Marguerite R Irvin, Hieab Adams, Sylvia Wassertheil-Smoller, Kaare Christensen, Mohammad A Ikram, Tatjana Rundek, Bradford B Worrall, G Mark Lathrop, Moeen Riaz, Eleanor M Simonsick, Janika Kõrv, Paulo H C França, Ramin Zand, Kameshwar Prasad, Ruth Frikke-Schmidt, Frank-Erik De Leeuw, Thomas Liman, Karl Georg Haeusler, Ynte M Ruigrok, Peter Ulrich Heuschmann, W T Longstreth, Keum Ji Jung, Lisa Bastarache, Guillaume Paré, Scott M Damrauer, Daniel I Chasman, Jerome I Rotter, Christopher D Anderson, John-Anker Zwart, Teemu J Niiranen, Myriam Fornage, Yung-Po Liaw, Sudha Seshadri, Israel Fernández-Cadenas, Robin G Walters, Christian T Ruff, Mayowa O Owolabi, Jennifer E Huffman, Lili Milani, Yoichiro Kamatani, Martin Dichgans, Stephanie Debette

Faculty, Staff and Student Publications

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary …


Ovarian Steroid Cell Tumors, Not Otherwise Specified: Analysis Of Nine Cases With A Literature Review, Mengyan Lin, Kechun Bao, Lingjia Lu, Shuhang Xu, Yun Liang, Xiaodong Cheng, Fenfen Wang Nov 2022

Ovarian Steroid Cell Tumors, Not Otherwise Specified: Analysis Of Nine Cases With A Literature Review, Mengyan Lin, Kechun Bao, Lingjia Lu, Shuhang Xu, Yun Liang, Xiaodong Cheng, Fenfen Wang

Faculty, Staff and Student Publications

BACKGROUND: Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS), are rare, with few large studies. The purpose of this study was to analyze the clinical features, prognosis, and treatment choices for these patients of different age groups.

METHODS: This was a retrospective study. We identified nine cases of ovarian steroid cell tumor, not otherwise specified, confirmed by post-operative histopathological examination, and analyzed clinical features, surgical procedures, and follow up outcomes. We also reviewed cases reports of ovarian steroid cell tumors, not otherwise specified.

RESULTS: A total of nine cases were included. The age range was 9-68 years (mean, 41.89 …


Cardiovascular Outcomes In Patients With Chronic Kidney Disease And Covid-19: A Multi-Regional Data-Linkage Study, Emilie J Lambourg, Peter J Gallacher, Robert W Hunter, Moneeza Siddiqui, Eve Miller-Hodges, James D Chalmers, Dan Pugh, Neeraj Dhaun, Samira Bell Nov 2022

Cardiovascular Outcomes In Patients With Chronic Kidney Disease And Covid-19: A Multi-Regional Data-Linkage Study, Emilie J Lambourg, Peter J Gallacher, Robert W Hunter, Moneeza Siddiqui, Eve Miller-Hodges, James D Chalmers, Dan Pugh, Neeraj Dhaun, Samira Bell

Faculty, Staff and Student Publications

BACKGROUND: Data describing cardiovascular outcomes in patients with coronavirus disease 2019 (COVID-19) and chronic kidney disease (CKD) are lacking. We compared cardiovascular outcomes of patients with and without COVID-19, stratified by CKD status.

METHODS: This retrospective, multi-regional data-linkage study utilised individual patient-level data from two Scottish cohorts. All patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Cohort 1 between 1 February 2020 and 31 March 2021 and in Cohort 2 between 28 February 2020 and 8 February 2021 were included.

RESULTS: Overall, 86 964 patients were tested for SARS-CoV-2. There were 36 904 patients (mean±sd age 61±21 …


International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lag-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah Nov 2022

International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lag-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah

Faculty, Staff and Student Publications

BACKGROUND: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG.

METHODS: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient …


Immune Dysfunction Signatures Predict Outcomes And Define Checkpoint Blockade-Unresponsive Microenvironments In Acute Myeloid Leukemia, Sergio Rutella, Jayakumar Vadakekolathu, Francesco Mazziotta, Stephen Reeder, Tung-On Yau, Rupkatha Mukhopadhyay, Benjamin Dickins, Heidi Altmann, Michael Kramer, Hanna A Knaus, Bruce R Blazar, Vedran Radojcic, Joshua F Zeidner, Andrea Arruda, Bofei Wang, Hussein A Abbas, Mark D Minden, Sarah K Tasian, Martin Bornhäuser, Ivana Gojo, Leo Luznik Nov 2022

Immune Dysfunction Signatures Predict Outcomes And Define Checkpoint Blockade-Unresponsive Microenvironments In Acute Myeloid Leukemia, Sergio Rutella, Jayakumar Vadakekolathu, Francesco Mazziotta, Stephen Reeder, Tung-On Yau, Rupkatha Mukhopadhyay, Benjamin Dickins, Heidi Altmann, Michael Kramer, Hanna A Knaus, Bruce R Blazar, Vedran Radojcic, Joshua F Zeidner, Andrea Arruda, Bofei Wang, Hussein A Abbas, Mark D Minden, Sarah K Tasian, Martin Bornhäuser, Ivana Gojo, Leo Luznik

Faculty, Staff and Student Publications

Background

Immune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of senescent-like CD8+ T cells and whether they have prognostic relevance.

METHODS

We analyzed NanoString, bulk RNA-Seq and single-cell RNA-Seq data from independent clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB).

Results

We show that senescent-like bone marrow CD8+ T cells were impaired in killing autologous AML blasts and that their proportion negatively correlated with overall survival …


Clinical Impact Of Ceftriaxone Resistance In Escherichia Coli Bloodstream Infections: A Multicenter Prospective Cohort Study, Pranita D Tamma, Lauren Komarow, Lizhao Ge, Julia Garcia-Diaz, Erica S Herc, Yohei Doi, Cesar A Arias, Owen Albin, Elie Saade, Loren G Miller, Jesse T Jacob, Michael J Satlin, Martin Krsak, W Charles Huskins, Sorabh Dhar, Samuel A Shelburne, Carol Hill, Keri R Baum, Minal Bhojani, Kerryl E Greenwood-Quaintance, Suzannah M Schmidt-Malan, Robin Patel, Scott R Evans, Henry F Chambers, Vance G Fowler, David Van Duin, Antibacterial Resistance Leadership Group Nov 2022

Clinical Impact Of Ceftriaxone Resistance In Escherichia Coli Bloodstream Infections: A Multicenter Prospective Cohort Study, Pranita D Tamma, Lauren Komarow, Lizhao Ge, Julia Garcia-Diaz, Erica S Herc, Yohei Doi, Cesar A Arias, Owen Albin, Elie Saade, Loren G Miller, Jesse T Jacob, Michael J Satlin, Martin Krsak, W Charles Huskins, Sorabh Dhar, Samuel A Shelburne, Carol Hill, Keri R Baum, Minal Bhojani, Kerryl E Greenwood-Quaintance, Suzannah M Schmidt-Malan, Robin Patel, Scott R Evans, Henry F Chambers, Vance G Fowler, David Van Duin, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Background

Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common.

Methods

This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding.

Results

Notable differences between patients infected with CRO-R and CRO-S …


Protein Profiling By Reverse Phase Protein Array (Rppa) In Classical Hairy Cell Leukemia (Hcl) And Hcl-Variant, Fieke W Hoff, Ti'ara L Griffen, Yihua Qiu, Steven M Kornblau Nov 2022

Protein Profiling By Reverse Phase Protein Array (Rppa) In Classical Hairy Cell Leukemia (Hcl) And Hcl-Variant, Fieke W Hoff, Ti'ara L Griffen, Yihua Qiu, Steven M Kornblau

Faculty, Staff and Student Publications

Classical hairy cell leukemia (HCL-c) and HCL variant (HCL-v) are recognized as separate entities with HCL-v having significantly shorter overall survival. Proteomic studies, shown to be prognostic in various forms of leukemia, have not been performed in HCL. We performed reverse phase protein array-based protein profiling with 384 antibodies in HCL-c (


Advances In Understanding Cancer-Associated Neurogenesis And Its Implications On The Neuroimmune Axis In Cancer, Ismail Yaman, Didem Ağaç Çobanoğlu, Tongxin Xie, Yi Ye, Moran Amit Nov 2022

Advances In Understanding Cancer-Associated Neurogenesis And Its Implications On The Neuroimmune Axis In Cancer, Ismail Yaman, Didem Ağaç Çobanoğlu, Tongxin Xie, Yi Ye, Moran Amit

Faculty, Staff and Student Publications

Nerves and immunologic mediators play pivotal roles in body homeostasis by interacting with each other through diverse mechanisms. The spread of nerves in the tumor microenvironment increases tumor cell proliferation and disease progression, and this correlates with poor patient outcomes. The effects of sympathetic and parasympathetic nerves on cancer regulation are being investigated. Recent findings demonstrate the possibility of developing therapeutic strategies that target the tumor microenvironment and its components such as immune cells, neurotransmitters, and extracellular vesicles. Therefore, examining and understanding the mechanisms and pathways associated with the sympathetic and parasympathetic nervous systems, neurotransmitters, cancer-derived mediators and their interactions …


International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lap-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah Nov 2022

International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lap-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah

Faculty, Staff and Student Publications

BACKGROUND: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG.

METHODS: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient …