Medical Specialties Commons^™

Repeated Out-Of-Africa Expansions Of Helicobacter Pylori Driven By Replacement Of Deleterious Mutations, Harry A Thorpe, Elise Tourrette, Koji Yahara, Filipa F Vale, Siqi Liu, Mónica Oleastro, Teresa Alarcon, Tsachi-Tsadok Perets, Saeid Latifi-Navid, Yoshio Yamaoka, Beatriz Martinez-Gonzalez, Ioannis Karayiannis, Timokratis Karamitros, Dionyssios N Sgouras, Wael Elamin, Ben Pascoe, Samuel K Sheppard, Jukka Ronkainen, Pertti Aro, Lars Engstrand, Lars Agreus, Sebastian Suerbaum, Kaisa Thorell, Daniel Falush

Faculty, Staff and Students Publications

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying …

Post-Transcatheter Aortic Valve Replacement (Tavr) Vascular Complications: Femoral Artery Minimal Surgical Access Versus Percutaneous Approach, Ahmed A. Arifi, Mohamed Belgaith, Kamal Ayoup, Fawaz Al Mutairi, Hani N Al Kattan, Elanany Mohamed

Journal of the Saudi Heart Association

Introduction: Percutaneous transfemoral access approach for the transcatheter aortic valve implantation (TAVI) is still associated with significant vascular complications. Hence, evaluation of best techniques for the reduction of vascular injury via the femoral access remains a key subject of research.

Aim: We report on a single centre’s experience with TAVI performed via the Femoral Artery Minimal Surgical Access (MSA) and percutaneous approach (PC). The primary endpoints were to evaluate the incidents of vascular complications by comparing the MSA versus the PC approach according to the VARC-2 criteria. The secondary endpoint included the impact of vascular complications on the in-hospital 30-day …

Treatment Of Severe Swallowing Dysfunction In Systemic Sclerosis With Ivig: Role Of Antimuscarinic Antibodies, Fabian A Mendoza, Anthony J. Dimarino, Sidney Cohen, Christopher Adkins, Shady Abdelbaki, Satish Rattan, Christopher Cao, Susie Denuna-Rivera, Sergio A. Jimenez

Division of Gastroenterology and Hepatology Faculty Papers

Oropharyngeal and esophageal dysmotility can cause serious clinical complications such as aspiration pneumonia, cachexia, and sarcopenia, with a resulting increase in mortality and disability. The current standard of care for the treatment of SSc-associated swallowing dysfunction is mainly supportive, although severe cases are usually refractory to conventional management. Recent studies have shown that the abnormal production of functional autoantibodies such as anti-cholinergic muscarinic receptor III antibodies may participate in the pathogenesis of SSc-associated gastrointestinal dysmotility and may provide a novel target for therapeutic intervention. We describe two patients with severe and rapid onset of SSc-associated severe swallowing dysfunction and esophageal …

Simultaneous Onset Of Haematological Malignancy And Covid: An Epicovideha Survey, Chiara Cattaneo, Jon Salmanton-García, Francesco Marchesi, Shaimaa El-Ashwah, Federico Itri, Barbora Weinbergerová, Maria Gomes Da Silva, Michelina Dargenio, Julio Dávila-Valls, Natasha Ali

Department of Pathology and Laboratory Medicine

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines.
Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022.
Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients …

Frosted Branch Angiitis Presenting After A Sars-Cov-2 Infection., Akhila Alapati, Nathaniel Cameron, Sean Gratton, Erin Stahl, Mary Champion

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To report a case of frosted branch angiitis presenting in a pediatric patient with unremarkable laboratory work-up apart from SARS-CoV-2 IgG antibodies.

OBSERVATIONS: Less than four weeks after a SARS-CoV-2 infection, a 10 year-old female presented to the emergency department with severe headache and intermittent fevers. During her hospital admission, the ophthalmology service was consulted for blurry vision. Subsequent eye examination revealed frosted branch angiitis. The patient initially received intravenous corticosteroids but was escalated to plasmapheresis to achieve resolution of her symptoms. Outpatient maintenance therapy consisted of an oral Prednisone taper and Infliximab infusion.

CONCLUSION AND IMPORTANCE: This case …

Erk Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro And In Vivo, Yang Yu, Yanling Zhao, Jongmin Choi, Zhongcheng Shi, Linjie Guo, John Elizarraras, Andy Gu, Feng Cheng, Yanxin Pei, Dai Lu, Muller Fabbri, Saurabh Agarwal, Chunchao Zhang, Sung Yun Jung, Jennifer H Foster, Jianhua Yang

Faculty, Staff and Students Publications

Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Approximately 80% of relapsed NB show RAS-MAPK pathway mutations that activate ERK, resulting in the promotion of cell proliferation and drug resistance. Ulixertinib, a first-in-class ERK-specific inhibitor, has shown promising antitumor activity in phase 1 clinical trials for advanced solid tumors. Here, we show that ulixertinib significantly and dose-dependently inhibits cell proliferation and colony formation in different NB cell lines, including PDX cells. Transcriptomic analysis revealed that ulixertinib extensively inhibits different oncogenic and neuronal developmental pathways, including EGFR, VEGF, WNT, MAPK, NGF, and NTRK1. The proteomic analysis further revealed …

Targeting The Mdm2-P53 Pathway In Dedifferentiated Liposarcoma, Raymond S Traweek, Brandon M Cope, Christina L Roland, Emily Z Keung, Elise F Nassif, Derek J Erstad

Faculty, Staff and Student Publications

Dedifferentiated liposarcoma (DDLPS) is an aggressive adipogenic cancer with poor prognosis. DDLPS tumors are only modestly sensitive to chemotherapy and radiation, and there is a need for more effective therapies. Genetically, DDLPS is characterized by a low tumor mutational burden and frequent chromosomal structural abnormalities including amplification of the 12q13-15 chromosomal region and the MDM2 gene, which are defining features of DDLPS. The MDM2 protein is an E3 ubiquitin ligase that targets the tumor suppressor, p53, for proteasomal degradation. MDM2 amplification or overexpression in human malignancies is associated with cell-cycle progression and worse prognosis. The MDM2-p53 interaction has thus garnered …

Sars-Cov-2 Spike Conformation Determines Plasma Neutralizing Activity Elicited By A Wide Panel Of Human Vaccines, John E. Bowen, Young-Jun Park, Cameron Stewart, Jack T. Brown, William K. Sharkey, Alexandra C. Walls, Anshu Joshi, Kumail Ahmed, Asefa Shariq, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated …

De Novo Identification Of Microbial Contaminants In Low Microbial Biomass Microbiomes With Squeegee, Yunxi Liu, R A Leo Elworth, Michael D Jochum, Kjersti M Aagaard, Todd J Treangen

Faculty, Staff and Students Publications

Computational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low-biomass environments. Contamination from DNA extraction kits or sampling lab environments leaves taxonomic "bread crumbs" across multiple distinct sample types. Here we describe Squeegee, a de novo contamination detection tool that is based upon this principle, allowing the detection of microbial contaminants when negative controls are unavailable. On the low-biomass samples, we compare Squeegee predictions to experimental negative control data and show that …

Assessing The Contribution Of Rare Genetic Variants To Phenotypes Of Chronic Obstructive Pulmonary Disease Using Whole-Genome Sequence Data, Wonji Kim, Julian Hecker, R Graham Barr, Eric Boerwinkle, Brian Cade, Adolfo Correa, Josée Dupuis, Sina A Gharib, Leslie Lange, Stephanie J London, Alanna C Morrison, George T O'Connor, Elizabeth C Oelsner, Bruce M Psaty, Ramachandran S Vasan, Susan Redline, Stephen S Rich, Jerome I Rotter, Bing Yu, Christoph Lange, Ani Manichaikul, Jin J Zhou, Tamar Sofer, Edwin K Silverman, Dandi Qiao, Michael H Cho, Nhlbi Trans-Omics In Precision Medicine (Topmed) Consortium And Topmed Lung Working Group

Faculty, Staff and Students Publications

Rationale: Genetic variation has a substantial contribution to chronic obstructive pulmonary disease (COPD) and lung function measurements. Heritability estimates using genome-wide genotyping data can be biased if analyses do not appropriately account for the nonuniform distribution of genetic effects across the allele frequency and linkage disequilibrium (LD) spectrum. In addition, the contribution of rare variants has been unclear.

Objectives: We sought to assess the heritability of COPD and lung function using whole-genome sequence data from the Trans-Omics for Precision Medicine program.

Methods: Using the genome-based restricted maximum likelihood method, we partitioned the genome into bins based on minor allele frequency …

Lupus Enteritis In The Absence Of A Lupus Flare. A Case Report And Review Of Literature, Fatima Halilu, Anum Qureshi, Brenton Nash

Journal of Community Hospital Internal Medicine Perspectives

Lupus enteritis is a rare manifestation seen in systemic lupus erythematosus (SLE). Its diagnosis can be challenging as symptoms frequently overlap many gastrointestinal disorders, imaging findings are not specific, and endoscopic features are infrequently diagnostic. Moreover, enteritis can occur in isolation without other systemic manifestations or even elevated inflammatory markers (1). Here is presented the case of a 22-year-old female with known SLE manifested by lupus nephritis complicated by end-stage renal disease who presented with abdominal pain. She had leukocytosis with thickened bowel loops, ascites, “target sign”, “comb sign” and patent abdominal vessels on CT imaging. The differential diagnoses considered …

Diabetes-Related Bias In Electronic Health Records And International Classification Of Diseases., Mihail Zilbermint

Journal of Community Hospital Internal Medicine Perspectives

Diabetes mellitus is a chronic health condition that affects the body's ability to convert food into energy. People living with diabetes, as well as doctors and hospitals, struggle to handle the challenge. Among these challenges is that the field of diabetology is filled with bias. People living with diabetes will say that “diabetes does not define them,” yet they often refer to themselves as “diabetics.” Doctors are frequently “trained” to call people “diabetics,” and I am one of them. Psychological consequences associated with diabetes and obesity bias and stigma have been previously reported studied. People with diabetes may experience stigma …

Getting Ahead: A Resident Led Quality Improvement Project To Increase Diabetic Nephropathy Screening In An Underserved Hispanic-Predominant Population, Stephanie Luu, Jose Rivera, Daniel Aragon, Victor Zamora, Irma Huayanay, Reham Majzoub, Andreina Baird, Cristina Escobar, Eric Sanchez, Juan Carlos Lopez-Alvarenga, Daniela Hernandez, Chelsea Chang

Journal of Community Hospital Internal Medicine Perspectives

Introduction: Diabetes is the leading cause of end-stage renal disease (ESRD) in the United States (US), with 37 million having chronic kidney disease. Despite national guidelines recommendations for diabetic nephropathy screening with urine albumin-to-creatinine ratio (UACR), less than 50% receive full screening.

Our Internal Medicine residents led a quality improvement project to increase diabetic nephropathy screening rate with UACR in our resident clinic by 50% in one academic year.

Methods: We conducted the resident-led quality improvement project from July 2021 to April 2022. We reviewed the electronic medical records (EMR) from our clinic pre-intervention July 2020 to June 2021 and …

Is Nippv Superior To Cpap In Maintaining Targeted Oxygen Saturation Ranges In Preterm Infants On Moderate Non-Invasive Respiratory Support?, Clifford Hegedus, William F. Bucher, Bs, Rrt-Nps, David Carola, Zubairul Aghai

Division of Pulmonary, Allergy, and Critical Care Medicine Posters

Background: Non-invasive positive pressure ventilation (NIPPV) and continuous positive airway pressure (CPAP) are non-invasive respiratory supports commonly used in preterm infants. There is conflicting data on the superiority between these two modes of non-invasive respiratory support. The objective of this study was to determine if oxygen saturation is more within the target range on NIPPV compared to CPAP using the data from histograms.

Methods: Retrospective analysis of premature neonates (< 1500 grams, gestational age < 30 weeks) admitted to the NICU for which oxygen saturation histogram data was available one day before and after the transition between NIPPV and CPAP. FiO2 at the time of data collection was greater than 21 percent. This histogram data, the percentage of time spent in certain SpO2 ranges, was compared before and after the de-escalation from NIPPV to CPAP or escalation from CPAP to NIPPV. FiO2 was additionally compared between the two modes of respiratory support.

Results: A total of 26 infants were included. The median gestational age was 25.5 weeks and the median weight of the infants was 792 grams. Among the 26 infants, there …

Experiences Of Participants In A Clinical Trial Of A Novel Radioactive Treatment For Advanced Prostate Cancer: A Nested, Qualitative Longitudinal Study, Bianca Viljoen, Michael S. Hofman, Suzanne K. Chambers, Jeff Dunn, Haryana M. Dhillon, Ian D. Davis, Nicholas Ralph

Research outputs 2022 to 2026

Objectives: Qualitative studies nested within clinical trials can provide insight into the treatment experience, how this evolves over time and where improved supportive care is required. The purpose of this qualitative study is to describe the lived experiences of men with advanced prostate cancer participating in the TheraP trial; a randomised trial of 177Lu-PSMA-617 compared with cabazitaxel chemotherapy. Methods: Fifteen men with advanced prostate cancer were recruited from the TheraP clinical trial with interviews conducted at three timepoints during the trial. An interpretative phenomenological approach was used, and interviews analysed using thematic analysis. This research paper reports the results from …

Uncovering The Biological Basis Of Control Energy: Structural And Metabolic Correlates Of Energy Inefficiency In Temporal Lobe Epilepsy, Xiaosong He, Lorenzo Caciagli, Linden Parkes, Jennifer Stiso, Teresa M. Karrer, Jason Z. Kim, Zhixin Lu, Tommaso Menara, Fabio Pasqualetti, Michael R. Sperling, Joseph I. Tracy, Dani S. Bassett

Department of Neurology Faculty Papers

Network control theory is increasingly used to profile the brain's energy landscape via simulations of neural dynamics. This approach estimates the control energy required to simulate the activation of brain circuits based on structural connectome measured using diffusion magnetic resonance imaging, thereby quantifying those circuits' energetic efficiency. The biological basis of control energy, however, remains unknown, hampering its further application. To fill this gap, investigating temporal lobe epilepsy as a lesion model, we show that patients require higher control energy to activate the limbic network than healthy volunteers, especially ipsilateral to the seizure focus. The energetic imbalance between ipsilateral and …

Changes In Prenatal Testing During The Covid-19 Pandemic, Sara C Handley, Rachel Ledyard, Lisbet S Lundsberg, Molly Passarella, Nancy Yang, Moeun Son, Kathryn Mckenney, Jay S. Greenspan, Kevin Dysart, Jennifer F Culhane, Heather H Burris

Department of Pediatrics Faculty Papers

Objective: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare delivery, including prenatal care. The study objective was to assess if timing of routine prenatal testing changed during the COVID-19 pandemic.

Methods: Retrospective observational cohort study using claims data from a regional insurer (Highmark) and electronic health record data from two academic health systems (Penn Medicine and Yale New Haven) to compare prenatal testing timing in the pre-pandemic (03/10/2018-12/31/2018 and 03/10/2019-12/31/2019) and early COVID-19 pandemic (03/10/2020-12/31/2020) periods. Primary outcomes were second trimester fetal anatomy ultrasounds and gestational diabetes (GDM) testing. A secondary analysis examined first trimester ultrasounds.

Results: The three datasets …

Evaluation Of Pharmaceutically Compounded Oral Caffeine On The Impact Of Medication Adherence And Risk Of Readmission Among Preterm Neonates: A Single-Center Quasi-Experimental Study, Gul Ambreen, Manoj Kumar, Amin Ali, Syed Akbar Ali Shah, Syed Muzaffar Saleem, Ayesha Tahir, Muhammad Sohail Salat, Muhammad Shahzad Aslam, Kashif Hussain

Department of Biological & Biomedical Sciences

Background: Caffeine is available in an ampoule, used via parenteral and enteral routes in preterm neonates to treat apnea of prematurity (AOP) in neonates of gestational age ≥ 35-40 weeks. A longer duration of therapy has a higher risk of medication non-adherence due to higher costs and inappropriate dosage forms. Pharmaceutically compounded oral caffeine (PCC) could be an appropriate alternate dosage form. The researchers aimed to determine the impact of PCC on medication-related factors influencing medication adherence (MA) and the frequency of hospital readmission with apnea (HRA) in preterm neonates.
Methods: We conducted a single-center quasi-experimental study for this quality …

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 …

Envenomation By The Green Bush Viper Atheris Squamigera, Sam T Ontiveros, Priya Srihari, Garret A Winkler, Jake Del Rosso, Julia Sobel, Richard F Clark, Alicia B Minns

Faculty, Staff and Student Publications

The Green Bush Viper, Atheris squamigera, is native to West and Central Africa and has few well reported envenomations. Bite victims experience dizziness, nausea, headache, regional lymphadenopathy, and localized edema. Most reports also detail severe effects including thrombocytopenia, coagulopathy, hemolysis, hemorrhage, or renal failure. Fatalities are reported, but poorly described. There is no specific antivenom for A. squamigera, but non-species specific antivenom has been reported helpful in several cases. We report the case of a 36-year-old woman who was bitten by a green bush viper and was treated with several non-species specific antivenoms. There were no complications to antivenom administration …

Multi-Organ Segmentation Of Abdominal Structures From Non-Contrast And Contrast Enhanced Ct Images, Cenji Yu, Chidinma P Anakwenze, Yao Zhao, Rachael M Martin, Ethan B Ludmir, Joshua S Niedzielski, Asad Qureshi, Prajnan Das, Emma B Holliday, Ann C Raldow, Callistus M Nguyen, Raymond P Mumme, Tucker J Netherton, Dong Joo Rhee, Skylar S Gay, Jinzhong Yang, Laurence E Court, Carlos E Cardenas

Faculty, Staff and Student Publications

Manually delineating upper abdominal organs at risk (OARs) is a time-consuming task. To develop a deep-learning-based tool for accurate and robust auto-segmentation of these OARs, forty pancreatic cancer patients with contrast-enhanced breath-hold computed tomographic (CT) images were selected. We trained a three-dimensional (3D) U-Net ensemble that automatically segments all organ contours concurrently with the self-configuring nnU-Net framework. Our tool's performance was assessed on a held-out test set of 30 patients quantitatively. Five radiation oncologists from three different institutions assessed the performance of the tool using a 5-point Likert scale on an additional 75 randomly selected test patients. The mean (± …

The Impact Of A New Stemi Hotline On Cardiovascular Outcomes In Stemi Patients Undergoing Primary Pci: A National Cohort Study, Fawaz Bardooli, Ali Alhashli, Omar Y. Alkhaja, Mohammed Faizal, Khaled Abdulmalek, Shaikha Musameh, Saad I. Mallah, Mohammed Alkhayat, Abdulkarim Abdulrahman

Journal of the Saudi Heart Association

Introduction: ST-Elevation myocardial infarction (STEMI) remains a common and challenging clinical condition with a high risk of mortality. STEMI complications are related directly to prolonged ischemia time. Mohamad Bin Khalifa Cardiac Centre (MKCC) established a national STEMI Hotline program on January 2022, to facilitate early detection and transfer of STEMI cases in the country to a dedicated tertiary cardiac center capable of performing primary PCI. Methods: This is an observational cohort study conducted on patients who presented to MKCC for primary PCI between August 2021 to February 2022. Patients who underwent primary PCI through referral from the newly developed STEMI …

Role Of Speckle Tracking Echocardiography To Predict Lv Dysfunction Post Mitral Valve Replacement Surgery For Severe Mitral Regurgitation, Parth Shanishwara, Pooja Vyas, Hasit Joshi, Iva Patel, Gajendra Dubey, Jignesh Patel, Shubham Sharma

Journal of the Saudi Heart Association

Background: Despite improvement in the surgical procedure and strictly following the guidelines for mitral valve replacement (MVR), left ventricular dysfunction still occurs. Novel echocardiographic indices can predict development of LV (left ventricle) dysfunction post MVR. LV-GLS (global longitudinal strain) derived from speckle tracking echocardiography, has been proposed as a novel measure to better depict latent LV dysfunction.

Methods:

A total of 100 patients with severe MR (mitral regurgitation) planned for MVR were included. Speckle tracking echocardiography was performed at baseline and at follow up post MVR. ROC (Receiver operating characteristics) curve was plotted to derive the cutoff value of …

Conducting A Supportive Oncology Clinical Trial During The Covid-19 Pandemic: Challenges And Strategies, Jie Deng, John N. Lukens, Joy C. Cohn, Erin Mcmenamin, Barbara Murphy, Bryan A. Spinelli, Niya Murphy, Alicia K. Steinmetz, Megan A. Landriau, Alexander Lin

Department of Physical Therapy Faculty Papers

The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances.

Trial registration: ClinicalTrials.gov, a service of the US National Institute of …

Covid-19 Newsletter (Vol. 144), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

Two Neuronal Peptides Encoded From A Single Transcript Regulate Mitochondrial Complex Iii In Drosophila, Justin A Bosch, Berrak Ugur, Israel Pichardo-Casas, Jordan Rabasco, Felipe Escobedo, Zhongyuan Zuo, Ben Brown, Susan Celniker, David A Sinclair, Hugo J Bellen, Norbert Perrimon

Duncan NRI Faculty and Staff Publications

Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open-reading frames (smORFs). Here, we describe two peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. Yet, Sloth1 and Sloth2 are not functionally redundant, and loss of either peptide causes animal lethality, reduced neuronal function, impaired mitochondrial function, and neurodegeneration. We provide evidence that Sloth1/2 are highly expressed in neurons, imported to mitochondria, and regulate mitochondrial complex III assembly. These results suggest that phenotypic analysis of smORF genes in Drosophila can provide a wealth of information on the biological functions of this poorly characterized class of …

Promotion Of A Synthetic Degradation Of Activated Stat6 By Parp-1 Inhibition: Roles Of Poly(Adp-Ribosyl)Ation, Calpains And Autophagy, Jeffrey Wang, Mohamed A. Ghonim, Salome V. Ibba, Hanh H. Luu, Yucel Aydin, Peter A. Greer, A. Hamid Boulares

School of Medicine Faculty Publications

Background: We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy. Methods: This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1−/− mice and Jurkat T cells to mimic Th2 inflammation. Results: We show that the role for PARP-1 in expression of IL-4-induced genes (e.g. gata-3) in splenocytes …

Association Between Preoperative Hemodialysis Timing And Postoperative Mortality In Patients With End-Stage Kidney Disease, Vikram Fielding-Singh, Matthew W Vanneman, Tristan Grogan, Jacques P Neelankavil, Wolfgang C Winkelmayer, Tara I Chang, Vincent X Liu, Eugene Lin

Faculty, Staff and Students Publications

Importance: For patients with end-stage kidney disease treated with hemodialysis, the optimal timing of hemodialysis prior to elective surgical procedures is unknown.

Objective: To assess whether a longer interval between hemodialysis and subsequent surgery is associated with higher postoperative mortality in patients with end-stage kidney disease treated with hemodialysis.

Design, setting, and participants: Retrospective cohort study of 1 147 846 procedures among 346 828 Medicare beneficiaries with end-stage kidney disease treated with hemodialysis who underwent surgical procedures between January 1, 2011, and September 30, 2018. Follow-up ended on December 31, 2018.

Exposures: One-, two-, or three-day intervals between the most …

Surgical Resection Of A Rare Primary Retroperitoneal Mucinous Borderline Tumor Of Müllerian Origin: A Case Report, Taylor R. Kavanagh, Nneamaka Nwaoduah, Scott D. Richard, Wilbur Bowne, Norman G Rosenblum

Department of Obstetrics and Gynecology Faculty Papers

•Primary retroperitoneal mucinous tumors (PRMTs) are a rare group of cystic neoplasms consisting of three subtypes.•PRMTs are histologically similar to ovarian mucinous tumors but lack true ovarian tissue.•PRMTs should be considered in the differential diagnosis when encountering retroperitoneal cystic lesions.•During surgical resection tumor disruption should be avoided.•Surgical resection alone provides durable disease control for mucinous borderline tumors of low malignant potential.

Antibody-Drug Conjugates For The Treatment Of Her2-Positive Breast Cancer, Mariana K Najjar, Sara G Manore, Angelina T Regua, Hui-Wen Lo

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted …