Medical Specialties Commons^™

Sgc-Camkk2-1: A Chemical Probe For Camkk2, Carrow Wells, Yi Liang, Thomas L Pulliam, Chenchu Lin, Dominik Awad, Benjamin Eduful, Sean O'Byrne, Mohammad Anwar Hossain, Carolina Moura Costa Catta-Preta, Priscila Zonzini Ramos, Opher Gileadi, Carina Gileadi, Rafael M Couñago, Brittany Stork, Christopher G Langendorf, Kevin Nay, Jonathan S Oakhill, Debarati Mukherjee, Luigi Racioppi, Anthony R Means, Brian York, Donald P Mcdonnell, John W Scott, Daniel E Frigo, David H Drewry

Faculty, Staff and Student Publications

The serine/threonine protein kinase calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) plays critical roles in a range of biological processes. Despite its importance, only a handful of inhibitors of CAMKK2 have been disclosed. Having a selective small molecule tool to interrogate this kinase will help demonstrate that CAMKK2 inhibition can be therapeutically beneficial. Herein, we disclose SGC-CAMKK2-1, a selective chemical probe that targets CAMKK2.

Correction: Carnitine Palmitoyl Transferase 1 A Is A Novel Diagnostic And Predictive Biomarker For Breast Cancer, Zheqiong Tan, Yaru Zou, Man Zhu, Zhenzhao Luo, Tangwei Wu, Chao Zheng, Aqing Xie, Hui Wang, Shiqiang Fang, Shuiyi Liu, Yong Li, Zhongxin Lu

Faculty, Staff and Students Publications

No abstract provided.

Outcomes Of Patients Treated For Hepatoblastoma With Low Alpha-Fetoprotein And/Or Small Cell Undifferentiated Histology: A Report From The Children's Hepatic Tumors International Collaboration (Chic), Angela D Trobaugh-Lotrario, Rudolf Maibach, Daniel C Aronson, Arun Rangaswami, Beate Häberle, Allison F O'Neill, Irene Schmid, Marc Ansari, Tomoro Hishiki, Sarangarajan Ranganathan, Rita Alaggio, Ronald R De Krijger, Yukichi Tanaka, Soo-Jin Cho, Christian Vokuhl, Rebecca Maxwell, Mark Krailo, Eiso Hiyama, Piotr Czauderna, Milton Finegold, James H Feusner, Marcio H Malogolowkin, Rebecka L Meyers, Dolores Lopez-Terrada

Faculty, Staff and Students Publications

Small cell undifferentiated (SCU) histology and alpha-fetoprotein (AFP) levels below 100 ng/mL have been reported as poor prognostic factors in hepatoblastoma (HB); subsequent studies reported SMARCB1 mutations in some SCU HBs confirming the diagnosis of rhabdoid tumor. The Children's Hepatic tumors International Collaboration (CHIC) database was queried for patients with HB who had AFP levels less than 100 ng/mL at diagnosis or were historically diagnosed as SCU HBs. Seventy-three of 1605 patients in the CHIC database were originally identified as SCU HB, HB with SCU component, or HB with low AFP levels. Upon retrospective review, they were re-classified as rhabdoid …

Feasibility Of Group-Based Implementation Facilitation For Video Telemental Health, Anthony H Ecker, Giselle Day, Amber B Amspoker, Jennifer L Bryan, Stephanie C Day, Miryam Wassef, Kendra Weaver, Jan Lindsay

Faculty, Staff and Students Publications

Video telehealth experienced rapid growth throughout the COVID-19 pandemic in many healthcare sectors, including mental health. The Veterans Health Administration’s video telehealth platform, VA Video Connect, has been widely used to reach veterans who may have experienced difficulty accessing care, such as those living in rural areas or other barriers (e.g., transportation). Implementing VVC requires a multifaceted approach, including training providers on technical skills, increasing access to equipment for providers and veterans, and integrating VVC within the culture and processes of the clinic unit. Prior successful VVC implementation efforts in rural areas have focused on simultaneous one-on-one provider and leadership …

Covid-19 Newsletter (Vol. 152), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

A Quality Improvement Project To Reduce Rates Of Deep Sternal Wound Infections Among Adult Cardiovascular Surgery Patients With A Sternotomy Approach, Cole Gatzke, Samantha Porcher

Nursing DNP Projects

Background: An increase in deep sternal wound infections (DSWI) within the cardiovascular surgery (CVS) department at a large midwestern teaching hospital among adult patients with an open sternotomy approach. Objective: To reduce the DSWI rate within the hospital’s CVS department. Methods: After gathering stakeholder input and observing the perioperative process, an extensive review of current literature was conducted to address the problem. Interventions that had literature support were then reanalyzed with stakeholder input for implementation selection, along with a cost-benefit analysis. A pilot was designed applying the Posthorax™ Pro Sternal Support Vest for adult cardiac surgery patients with a sternotomy …

Postibrutinib Relapse Outcomes For Patients With Marginal Zone Lymphoma, Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K. Moyo, Nishitha Reddy, Julia Sheets, David M. Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C. Churnetski, Andrew Hsu, Luke Zurbriggen, Xiao-Wei Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F. Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Timothy S. Oh, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A. David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P. Kenkre, Adam J. Olszewski, Jonathon B. Cohen, Neil Palmisiano, Elvira Umyarova, Ryan A. Wilcox, Farrukh T. Awan, Juan Pablo Alderuccio, Stefan K. Barta, Natalie S. Grover, Nilanjan Ghosh, Nancy L. Bartlett, Alex F. Herrera, Geoffrey Shouse

Department of Medicine Faculty Papers

No abstract provided.

Alcoholic Vs. Nonalcoholic Steatohepatitis: Vascular Branching Heterogeneity On Magnetic Resonance Imaging As A Diagnostic Marker, Daniel Garrido, Nicholas Noverati, Justin Robbins, Jaydev K. Dave, Haresh V. Naringrekar, Donald Mitchell, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Background and aims: Distinguishing alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) with biopsy alone is often difficult without a reliable clinical context. A novel finding on liver imaging, perivascular branching heterogeneity, has shown promise in distinguishing between these chronic liver diseases. Our study investigated the role of this finding on imaging to differentiate between ASH and NASH. The aim of this study was to determine the utility and reproducibility of this novel radiographic marker to help distinguish ASH from NASH.

Methods: This was a retrospective cohort study conducted between 2016 and 2020 in patients with both liver biopsy-confirmed steatohepatitis/chronic hepatitis …

Efficacy Of Eltrombopag With Immunosuppressive Therapy For Children With Acquired Aplastic Anemia, Yufei Zhao, Wenrui Yang, Xin Zhao, Xiangrong Hu, Jing Hu, Xu Liu, Jianping Li, Lei Ye, Youzhen Xiong, Yang Yang, Baohang Zhang, Xiaoxia Li, Xiawan Yang, Yimeng Shi, Guangxin Peng, Yuan Li, Huihui Fan, Kang Zhou, Liping Jing, Li Zhang, Fengkui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial.

METHODS: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) …

Diverticular Disease And Cancer Risk: More Than A Gut Feeling, Veronika Fedirko, Scott Kopetz, Carrie R Daniel

Faculty, Staff and Student Publications

No abstract provided.

Differential Co-Expression Networks Of The Gut Microbiota Are Associated With Depression And Anxiety Treatment Resistance Among Psychiatric Inpatients, Dominique S Thompson, Chenlian Fu, Tanmay Gandhi, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Julia K Hadden, Marianne Carlson, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

BACKGROUND: Comorbid anxiety and depression are common and are associated with greater disease burden than either alone. Our recent efforts have identified an association between gut microbiota dysfunction and severity of anxiety and depression. In this follow-up, we applied Differential Co-Expression Analysis (DiffCoEx) to identify potential gut microbiota biomarker(s) candidates of treatment resistance among psychiatric inpatients.

METHODS: In a sample of convenience, 100 psychiatric inpatients provided clinical data at admission and discharge; fecal samples were collected early during the hospitalization. Whole genome shotgun sequencing methods were used to process samples. DiffCoEx was used to identify clusters of microbial features significantly …

Predictors Of Success In Establishing Orthotopic Patient-Derived Xenograft Models Of Triple Negative Breast Cancer, Gloria V Echeverria, Shirong Cai, Yizheng Tu, Jiansu Shao, Emily Powell, Abena B Redwood, Yan Jiang, Aaron Mccoy, Amanda L Rinkenbaugh, Rosanna Lau, Alexander J Trevarton, Chunxiao Fu, Rebekah Gould, Elizabeth E Ravenberg, Lei Huo, Rosalind Candelaria, Lumarie Santiago, Beatriz E Adrada, Deanna L Lane, Gaiane M Rauch, Wei T Yang, Jason B White, Jeffrey T Chang, Stacy L Moulder, W Fraser Symmans, Susan G Hilsenbeck, Helen Piwnica-Worms

Faculty, Staff and Student Publications

Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. We established orthotopic PDX models of triple negative breast cancer (TNBC) from the primary breast tumors of patients prior to and following neoadjuvant chemotherapy (NACT) while they were enrolled in the ARTEMIS trial (NCT02276443). Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of Adriamycin and cyclophosphamide (AC, mid-NACT), and in cases of AC-resistance, after a 3-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a …

Impact Of Enteropathogens On Faltering Growth In A Resource-Limited Setting, Furqan Kabir, Junaid Iqbal, Zehra Jamil, Najeeha Talat Iqbal, Fatima Aziz, Adil Kalam, Sahrish Muneer, Aneeta Hotwani, Sheraz Ahmed, Fayyaz Umrani, Sana Syed, Kamran Sadiq, Syed Asad Ali

Department of Paediatrics and Child Health

Introduction: Environmental enteropathy is an important contributor to childhood malnutrition in the developing world. Chronic exposure to fecal pathogens leads to alteration in intestinal structure and function, resulting in impaired gut immune function, malabsorption, and growth faltering leading to environmental enteropathy.
Methods: A community-based intervention study was carried out on children till 24 months of age in Matiari district, Pakistan. Blood and fecal specimens were collected from the enrolled children aged 3-6 and 9 months. A real-time PCR-based TaqMan array card (TAC) was used to detect enteropathogens.
Results: Giardia, Campylobacter spp., enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), …

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …

A Bioengineered Probiotic For The Oral Delivery Of A Peptide Kv13 Channel Blocker To Treat Rheumatoid Arthritis, Yuqing Wang, Duolong Zhu, Laura C Ortiz-Velez, Jacob L Perry, Michael W Pennington, Joseph M Hyser, Robert A Britton, Christine Beeton

Faculty, Staff and Students Publications

New therapeutics that combine efficacy with limited side effects and can be delivered noninvasively are needed to adequately treat patients with rheumatoid arthritis (RA) and other autoimmune diseases. Kv1.3 channel-expressing CCR7− effector memory T (TEM) lymphocytes are significant players in the pathogenesis of multiple autoimmune diseases, and blocking Kv1.3 reduces disease severity in rat models of RA and patients with plaque psoriasis. However, peptide therapeutics require repeated injections, reducing patient compliance. We used a bioengineered Lactobacillus reuteri as an oral delivery method of a Kv1.3 blocker for immunomodulation in rat models of atopic dermatitis and RA. This study demonstrates a …

Prospective Association Of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis, Amanda E Paluch, Shivangi Bajpai, Marcel Ballin, David R Bassett, Thomas W Buford, Mercedes R Carnethon, Ariel Chernofsky, Erin E Dooley, Ulf Ekelund, Kelly R Evenson, Deborah A Galuska, Barbara J Jefferis, Lingsong Kong, William E Kraus, Martin G Larson, I-Min Lee, Charles E Matthews, Robert L Newton, Anna Nordström, Peter Nordström, Priya Palta, Alpa V Patel, Kelley Pettee Gabriel, Carl F Pieper, Lisa Pompeii, Erika Rees-Punia, Nicole L Spartano, Ramachandran S Vasan, Peter H Whincup, Shengping Yang, Janet E Fulton, Steps For Health Collaborative

Faculty, Staff and Students Publications

Background: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines.

Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional …

Disabling Uncompetitive Inhibition Of Oncogenic Idh Mutations Drives Acquired Resistance, Junhua Lyu, Yuxuan Liu, Lihu Gong, Mingyi Chen, Yazan F Madanat, Yuannyu Zhang, Feng Cai, Zhimin Gu, Hui Cao, Pranita Kaphle, Yoon Jung Kim, Fatma N Kalkan, Helen Stephens, Kathryn E Dickerson, Min Ni, Weina Chen, Prapti Patel, Alice S Mims, Uma Borate, Amy Burd, Sheng F Cai, C Cameron Yin, M James You, Stephen S Chung, Robert H Collins, Ralph J Deberardinis, Xin Liu, Jian Xu

Faculty, Staff and Student Publications

Mutations in IDH genes occur frequently in acute myeloid leukemia (AML) and other human cancers to generate the oncometabolite R-2HG. Allosteric inhibition of mutant IDH suppresses R-2HG production in a subset of patients with AML; however, acquired resistance emerges as a new challenge, and the underlying mechanisms remain incompletely understood. Here we establish isogenic leukemia cells containing common IDH oncogenic mutations by CRISPR base editing. By mutational scanning of IDH single amino acid variants in base-edited cells, we describe a repertoire of IDH second-site mutations responsible for therapy resistance through disabling uncompetitive enzyme inhibition. Recurrent mutations at NADPH …

A Molecular Switch Between Mammalian Mll Complexes Dictates Response To Menin-Mll Inhibition, Yadira M Soto-Feliciano, Francisco J Sánchez-Rivera, Florian Perner, Douglas W Barrows, Edward R Kastenhuber, Yu-Jui Ho, Thomas Carroll, Yijun Xiong, Disha Anand, Alexey A Soshnev, Leah Gates, Mary Clare Beytagh, David Cheon, Shengqing Gu, X Shirley Liu, Andrei V Krivtsov, Maximiliano Meneses, Elisa De Stanchina, Richard M Stone, Scott A Armstrong, Scott W Lowe, C David Allis

Faculty, Staff and Student Publications

Menin interacts with oncogenic MLL1-fusion proteins, and small molecules that disrupt these associations are in clinical trials for leukemia treatment. By integrating chromatin-focused and genome-wide CRISPR screens with genetic, pharmacologic, and biochemical approaches, we discovered a conserved molecular switch between the MLL1-Menin and MLL3/4-UTX chromatin-modifying complexes that dictates response to Menin-MLL inhibitors. MLL1-Menin safeguards leukemia survival by impeding the binding of the MLL3/4-UTX complex at a subset of target gene promoters. Disrupting the Menin-MLL1 interaction triggers UTX-dependent transcriptional activation of a tumor-suppressive program that dictates therapeutic responses in murine and human leukemia. Therapeutic reactivation of this program using CDK4/6 inhibitors …

Dance/Movement Therapy As A Holistic Approach To Diminish Health Discrepancies And Promote Wellness For People With Schizophrenia: A Review Of The Literature, Jacelyn Biondo

Department of Family & Community Medicine Faculty Papers

Individuals with a diagnosis of schizophrenia face a myriad of obstacles to wellness, beginning with diagnostic discrepancies including over- and misdiagnoses on the schizophrenia spectrum. People with schizophrenia experience profound amounts of stigmatization from the general population, their healthcare providers, and even themselves. Such stigmatization creates a barrier for wellness, poorer prognoses, and often limits adherence to physical and mental healthcare. Moreover, it can exacerbate the already stifling symptomatology of their diagnoses, including specific bodily-related symptomatology. Oftentimes, a diagnosis of schizophrenia disrupts one's relationship with their body including a diminished mind-body connection, decreased interoceptive awareness, and thus unsuccessful intra- and …

The Axillary View Typically Does Not Contribute To Decision Making In Care For Proximal Humeral Fractures, Alfadl A Abdulfattah, Hanan A Jawkhab, Altaf A Alhazmi, Nada A Alfaifi, Maryam A Sultan, Rajaa A Alnami, Nada Y Kenani, Shorooq A Hamzi, Shahd M Abu Sharha, Ibrahim M Dighriri

Faculty, Staff and Student Publications

Background: Helicobacter pylori (H. pylori) is a severe infection responsible for upper gastrointestinal symptoms (UGISs). Several causes of H. pylori infection include food ingestion and person-to-person transmission. Many lifestyle variables can affect the occurrence of UGISs such as coffee consumption and smoking.

Objective: To assess the association between smoking and coffee consumption and the occurrence of UGISs in patients with active H. pylori infection in Jazan city in Saudi Arabia.

Methodology: A descriptive cross-sectional research design was used to conduct the study between July 2022 and August 2022 in Jazan, southern Saudi Arabia. Male and female Saudis or …

Many People With Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma Benefit From Ibrutinib Treatment Up To 8 Years: A Plain Language Summary, Paul M Barr, Carolyn Owen, Tadeusz Robak, Alessandra Tedeschi, Osnat Bairey, Jan A Burger, Peter Hillmen, Claire Dearden, Sebastian Grosicki, Helen Mccarthy, Jian Yong Li, Fritz Offner, Carol Moreno, Mandy Jermain, Cathy Zhou, Emily Hsu, Anita Szoke, Thomas J Kipps, Paolo Ghia

Faculty, Staff and Student Publications

What is this summary about?: This is a plain language summary of a publication describing long-term results from the RESONATE-2 study with up to 8 years of follow-up. The original paper was published in Blood Advances in June 2022.

What were the results?: Researchers looked at 269 adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had not received any treatment for their CLL/SLL. Study participants were randomly divided into two groups: 136 participants received treatment with a drug called ibrutinib, and 133 participants received treatment with a drug called chlorambucil. Participants in the study were treated …

Trends And Racial/Ethnic Differences In Predictors Of Cervical Cancer Screening Among Us Women Ages 30-64 Years, Itunu O Sokale, Jane R Montealegre, Abiodun O Oluyomi, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Cervical cancer screening (CCS) participation has decreased in the United States over the last several decades, contributing to cervical cancer's sustained incidence and mortality. This study examined recent trends and racial/ethnic differences in predictors of CCS uptake among US women.

METHODS: We analyzed combined data from the 2016 to 2020 Behavioral Risk Factor Surveillance System (BRFSS) and included 235,713 women ages 30 to 64 years without a hysterectomy. We used simple linear regression to assess trends over time and multivariable logistic regression models to evaluate racial/ethnic differences in predictors of up-to-date CCS.

RESULTS: We found little change in CCS …

Evaluation Of Serum Concentration Of Acute-Phase Proteins (Haptoglobin And Serum Amyloid A) In The Affected Arabian Foals With Rhodococcosis, Ali Hassanpour, Sina Moghaddam

Faculty, Staff and Students Publications

BACKGROUND: Early detection of Rhodococcus equi pneumonia in foals is essential for horse health and for veterinarians.

OBJECTIVES: This study aimed to demonstrate the usefulness of assessing the serum concentration of acute-phase proteins (APPs) in the early diagnosis of pneumonia.

METHODS: The study evaluated APPs in 19 Arabian foals with R. equi pneumonia and compared them with 18 normal Arabian foals in equestrian clubs in Tabriz, Iran. Affected foals were identified through history, clinical findings and bacterial culture of tracheal washing. Biochemical methods and polymerase chain reaction tests were performed by examining the 16S rRNA and vapA genes to confirm …

Technology Meets Tils: Deciphering T Cell Function In The -Omics Era, William H Hudson, Andreas Wieland

Faculty, Staff and Students Publications

T cells are at the centerstage of cancer immunology due to their ability to recognize mutations within tumor cells and directly mediate cancer cell killing. Immunotherapies to rejuvenate exhausted T cell responses have transformed the clinical management of several malignancies. In parallel, the development of novel multidimensional analysis platforms such as single-cell RNA-sequencing and high-dimensional flow cytometry has yielded unprecedented insights into immune cell biology. This convergence has revealed substantial heterogeneity of tumor-infiltrating immune cells, both within single tumors, across tumor types, and among cancer patients. Here, we discuss the opportunities and challenges of studying the complex tumor microenvironment with …

Technology Meets Tils: Deciphering T Cell Function In The -Omics Era, William H Hudson, Andreas Wieland

Faculty, Staff and Students Publications

T cells are at the centerstage of cancer immunology due to their ability to recognize mutations within tumor cells and directly mediate cancer cell killing. Immunotherapies to rejuvenate exhausted T cell responses have transformed the clinical management of several malignancies. In parallel, the development of novel multidimensional analysis platforms such as single-cell RNA-sequencing and high-dimensional flow cytometry has yielded unprecedented insights into immune cell biology. This convergence has revealed substantial heterogeneity of tumor-infiltrating immune cells, both within single tumors, across tumor types, and among cancer patients. Here, we discuss the opportunities and challenges of studying the complex tumor microenvironment with …

Interdependent Progression Of Bidirectional Sister Replisomes In E Coli, Po Jui Chen, Anna B Mcmullin, Bryan J Visser, Qian Mei, Susan M Rosenberg, David Bates

Faculty, Staff and Students Publications

Bidirectional DNA replication complexes initiated from the same origin remain colocalized in a factory configuration for part or all their lifetimes. However, there is little evidence that sister replisomes are functionally interdependent, and the consequence of factory replication is unknown. Here, we investigated the functional relationship between sister replisomes in Escherichia coli, which naturally exhibits both factory and solitary configurations in the same replication cycle. Using an inducible transcription factor roadblocking system, we found that blocking one replisome caused a significant decrease in overall progression and velocity of the sister replisome. Remarkably, progression was impaired only if the block …

Histopathologic And Proteogenomic Heterogeneity Reveals Features Of Clear Cell Renal Cell Carcinoma Aggressiveness, Yize Li, Tung-Shing M Lih, Saravana M Dhanasekaran, Rahul Mannan, Lijun Chen, Marcin Cieslik, Yige Wu, Rita Jiu-Hsien Lu, David J Clark, Iga Kołodziejczak, Runyu Hong, Siqi Chen, Yanyan Zhao, Seema Chugh, Wagma Caravan, Nataly Naser Al Deen, Noshad Hosseini, Chelsea J Newton, Karsten Krug, Yuanwei Xu, Kyung-Cho Cho, Yingwei Hu, Yuping Zhang, Chandan Kumar-Sinha, Weiping Ma, Anna Calinawan, Matthew A Wyczalkowski, Michael C Wendl, Yuefan Wang, Shenghao Guo, Cissy Zhang, Anne Le, Aniket Dagar, Alex Hopkins, Hanbyul Cho, Felipe Da Veiga Leprevost, Xiaojun Jing, Guo Ci Teo, Wenke Liu, Melissa A Reimers, Russell Pachynski, Alexander J Lazar, Arul M Chinnaiyan, Brian A Van Tine, Bing Zhang, Karin D Rodland, Gad Getz, D R Mani, Pei Wang, Feng Chen, Galen Hostetter, Mathangi Thiagarajan, W Marston Linehan, David Fenyö, Scott D Jewell, Gilbert S Omenn, Rohit Mehra, Maciej Wiznerowicz, Ana I Robles, Mehdi Mesri, Tara Hiltke, Eunkyung An, Henry Rodriguez, Daniel W Chan, Christopher J Ricketts, Alexey I Nesvizhskii, Hui Zhang, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 …

Rota Ablation – When There Is No Other Option. A Complex Case Of 86 Years Old Male With Multiple Comorbids Presenting With Stemi, Tooba Sahar, Asaad Akbar Khan, Taha Abdul Rehman, Danish Iltaf Satti

Journal of Community Hospital Internal Medicine Perspectives

The aim of this report is to explore the direct and long-term outcome in a high risk patient who was treated with rotational atherectomy (RA) to assist the placement of drug eluting stents in heavily calcified lesions. The patient presented with acute STEMI and had severely calcified Left main stem (LMS) disease, requiring plaque modification before coronary angioplasty and stent implantation. As the patient was elderly, with multiple comorbids including a number of coronary interventions, a decision of conservative management was made. Patient then re-presented with typical chest pain and pulmonary edema. A Heart Team meeting was called and high …

Reply To The Letter To The Editor Titled “Before Blaming Legionella For Severe Rhabdomyolysis, Consider Alternative Triggers”, Harish Gopalakrishna, Ahmad Al-Abdouh, Gayatri Nair, Vinod Solipuram, Ammer Bekele

Journal of Community Hospital Internal Medicine Perspectives

No abstract provided.

Refractory Age-Related Macular Degeneration Due To Concurrent Central Serous Chorioretinopathy In Previously Well-Controlled Eyes, Chikako Hara, Taku Wakabayashi, Kaori Sayangi, Kohji Nishida

Wills Eye Hospital Papers

Background: During the treatment of age-related macular degeneration with anti-vascular endothelial growth factor (VEGF) drugs, we often see cases with anti-VEGF-resistant refractory subretinal fluid. In this report, we present two cases of anti-VEGF-resistant refractory age-related macular degeneration (AMD) due to the concurrent development of central serous chorioretinopathy (CSCR) in eyes previously well controlled with intravitreal anti-VEGF injections. Case presentation: Two patients underwent intravitreal aflibercept for the treatment of neovascular AMD. Initially, both patients responded well to intravitreal aflibercept, resulting in the complete resolution of the subretinal fluid. However, both patients subsequently developed sudden-onset refractory subretinal fluid that did not respond …