Medical Specialties Commons^™

Harnessing The Therapeutic Vulnerability Of Mmr Heterogeneity In Colorectal Cancer, Gayathri Anandappa, Michael J Overman

Faculty, Staff and Student Publications

In a recent issue of Cancer Cell, Amodio and colleagues report an interesting method of modulating immunosurveillance in colorectal tumors with DNA mismatch repair (MMR) heterogeneity.1 By pharmacologically enriching the MMR deficient (MMRd) component using 6-thioguanine, they demonstrate improved tumor control in murine models.

Examining Stripes On A Herd Of Zebras: Impact Of Genomic Matching For Ultrarare Sarcomas In Phase 1 Clinical Trials (Samba 102), Justin T Moyers, Roberto Carmagnani Pestana, Jason Roszik, David S Hong, Aung Naing, Siqing Fu, Sarina Piha-Paul, Timothy A Yap, Daniel Karp, Jordi Rodon, Andy Livingston, Maria Alejandra Zarzour, Vinod Ravi, Shreyaskumar Patel, Robert S Benjamin, Joseph Ludwig, Cynthia Herzog, Ravin Ratan, Neeta Somaiah, Anthony Conley, Richard Gorlick, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Recently, the Connective Tissue Oncology Society published consensus guidelines for recognizing ultrarare sarcomas (URS), defined as sarcomas with an incidence ≤1 per 1,000,000. We assessed the outcomes of 56 patients with soft tissue, and 21 with bone sarcomas, enrolled in Phase 1 trials.

Experimental design: In this Sarcoma-Matched Biomarker Analysis (SAMBA-102 study), we reviewed records from patients on Phase 1 trials at the University of Texas MD Anderson Cancer Center between January 2013 and June 2021.

Results: Among 587 sarcomas, 106 (18.1%) were classified as URS. Fifty (47%) were male, and the median age was 44.3 years (range, 19-82). …

Topical Antibiotic Treatment In Dermatology, Matthew Dallo, Kavina Patel, Adelaide A Hebert

Faculty, Staff and Student Publications

Many indications in dermatology can be effectively managed with topical antibiotics, including acne vulgaris, wound infections, secondarily infected dermatitis, and impetigo. Dermatologists must be familiar with the wide spectrum of topical antibiotics available, including indications, mechanisms of action, adverse events, and spectra of activity. Dermatologists must also keep antibiotic resistance in mind when utilizing these medications. Due to the widespread use of topical antibiotics and their importance in dermatology, a literature review was performed using a systematic search of PubMed and Google Scholar with the terms topical antibiotics, skin infections, dermatology, antimicrobials, and inflammatory dermatoses to identify English-language articles published …

Thrombectomy Outcomes With General Vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From The Extend-Ia Trials And Select Study, Amrou Sarraj, Gregory W Albers, Peter J Mitchell, Ameer E Hassan, Michael G Abraham, Spiros Blackburn, Gagan Sharma, Nawaf Yassi, Timothy J Kleinig, Darshan G Shah, Teddy Y Wu, Muhammad Shazam Hussain, Wondwoseen G Tekle, Santiago Ortega Gutierrez, Amin Nima Aghaebrahim, Diogo C Haussen, Gabor Toth, Deep Pujara, Ronald F Budzik, William Hicks, Nirav Vora, Randall C Edgell, Sabreena Slavin, Colleen G Lechtenberg, Laith Maali, Abid Qureshi, Lee Rosterman, Mohammad Ammar Abdulrazzak, Tareq Almaghrabi, Faris Shaker, Osman Mir, Ashish Arora, Sheryl Martin-Schild, Clark W Sitton, Leonid Churilov, Rishi Gupta, Maarten G Lansberg, Raul G Nogueira, James C Grotta, Geoffrey Alan Donnan, Stephen M Davis, Bruce C V Campbell

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice.

METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax > 10 seconds/Tmax > 6 seconds (good collaterals - HIR < 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes.

RESULTS: Of 725 treated with EVT, 299 (41%) received GA …

Biorisk Management, Laboratory Acquired Infections And Clinical Containment, Kashif Ali, Furqan Kabir, Esmeralda Meyer

Department of Paediatrics and Child Health

No abstract provided.

Computational Simulations Of Fabrication Of Aluminum-Based Josephson Junctions: Topological Aspects Of The Barrier Structure, Chuanbing Han, Huihui Sun, Fudong Liu, Xiangju Zhao, Zheng Shan

Faculty, Staff and Student Publications

Although the performance of qubits has been improved in recent years, the differences in the microscopic atomic structure of the Josephson junctions, the core devices prepared under different preparation conditions, are still underexplored. In this paper, the effects of the oxygen temperature and upper aluminum deposition rate on the topology of the barrier layer in the aluminum-based Josephson junctions have been presented by classical molecular dynamics simulations. We apply a Voronoi tessellation method to characterize the topology of the interface and central regions of the barrier layers. We find that when the oxygen temperature is 573 K and the upper …

Features Of Tumor-Microenvironment Images Predict Targeted Therapy Survival Benefit In Patients With Egfr-Mutant Lung Cancer, Shidan Wang, Ruichen Rong, Donghan M Yang, Junya Fujimoto, Justin A Bishop, Shirley Yan, Ling Cai, Carmen Behrens, Lynne D Berry, Clare Wilhelm, Dara Aisner, Lynette Sholl, Bruce E Johnson, David J Kwiatkowski, Ignacio I Wistuba, Paul A Bunn, John Minna, Guanghua Xiao, Mark G Kris, Yang Xie

Faculty, Staff and Student Publications

Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) are effective for many patients with lung cancer with EGFR mutations. However, not all patients are responsive to EGFR TKIs, including even those harboring EGFR-sensitizing mutations. In this study, we quantified the cells and cellular interaction features of the tumor microenvironment (TME) using routine H&E-stained biopsy sections. These TME features were used to develop a prediction model for survival benefit from EGFR TKI therapy in patients with lung adenocarcinoma and EGFR-sensitizing mutations in the Lung Cancer Mutation Consortium 1 (LCMC1) and validated in an independent LCMC2 cohort. In the validation …

Thrombectomy Outcomes With General Vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From The Extend-Ia Trials And Select Study., Amrou Sarraj, Gregory W Albers, Peter J Mitchell, Ameer E Hassan, Michael G Abraham, Spiros Blackburn, Gagan Sharma, Nawaf Yassi, Timothy J Kleinig, Darshan G Shah, Teddy Y Wu, Muhammad Shazam Hussain, Wondwoseen G Tekle, Santiago Ortega Gutierrez, Amin Nima Aghaebrahim, Diogo C Haussen, Gabor Toth, Deep Pujara, Ronald F Budzik, William Hicks, Nirav Vora, Randall C Edgell, Sabreena Slavin, Colleen G Lechtenberg, Laith Maali, Abid Qureshi, Lee Rosterman, Mohammad Ammar Abdulrazzak, Tareq Almaghrabi, Faris Shaker, Osman Mir, Ashish Arora, Sheryl Martin-Schild, Clark W Sitton, Leonid Churilov, Rishi Gupta, Maarten G Lansberg, Raul G Nogueira, James C Grotta, Geoffrey Alan Donnan, Stephen M Davis, Bruce C V Campbell

Neuroscience Articles

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice.

METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax > 10 seconds/Tmax > 6 seconds (good collaterals - HIR < 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes.

RESULTS: Of 725 treated with EVT, 299 (41%) received GA …

Physical Activity, Seasonal Sensitivity And Psychological Well-Being Of People Of Different Age Groups Living In Extreme Environments, Caren Alvarado, Matías Castillo-Aguilar, Valeska Villegas, Claudia Estrada Goic, Katherine Harris, Patricio Barria, Michele M Moraes, Thiago T Mendes, Rosa M E Arantes, Pablo Valdés-Badilla, Cristian Núñez-Espinosa

Faculty, Staff and Student Publications

Physical activity can prevent many organic and mental pathologies. For people living in extreme southern high-latitude environments, weather conditions can affect these activities, altering their psychological well-being and favoring the prevalence of seasonal sensitivity (SS). This study aims to determine the relationships between the practice of physical activity, seasonal sensitivity and well-being in people living in high southern latitudes. A cross-sectional study was conducted, using the Seasonal Pattern Assessment Questionnaire (SPAQ), applying a psychological well-being scale, and determining sports practice according to the recommendations of the World Health Organization (WHO) for the 370 male (n = 209; 55%) and female …

Mechanisms Of Mcl-1 Protein Stability Induced By Mcl-1 Antagonists In B-Cell Malignancies, Shady I Tantawy, Aloke Sarkar, Stefan Hubner, Zhi Tan, William G Wierda, Abdelraouf Eldeib, Shuxing Zhang, Steven Kornblau, Varsha Gandhi

Faculty, Staff and Student Publications

PURPOSE: Several MCL-1 inhibitors (MCL-1i), including AMG-176 and AZD5991, have shown promise in preclinical studies and are being tested for the treatment of hematologic malignancies. A unique feature of these agents is induction and stability of Mcl-1 protein; however, the precise mechanism is unknown. We aim to study the mechanism of MCL-1i-induced Mcl-1 protein stability.

EXPERIMENTAL DESIGN: Using several B-cell leukemia and lymphoma cell lines and primary chronic lymphocytic leukemia (CLL) lymphocytes, we evaluated molecular events associated with Mcl-1 protein stability including protein half-life, reverse-phase protein array, protein-protein interaction, phosphorylation, ubiquitination, and de-ubiquitination, followed by molecular simulation and modeling.

RESULTS: …

Automating The High-Throughput Screening Of Protein-Based Optical Indicators And Actuators, Jihwan Lee, Beatriz Campillo, Shaminta Hamidian, Zhuohe Liu, Matthew Shorey, François St-Pierre

Faculty, Staff and Students Publications

Over the last 25 years, protein engineers have developed an impressive collection of optical tools to interface with biological systems: indicators to eavesdrop on cellular activity and actuators to poke and prod native processes. To reach the performance level required for their downstream applications, protein-based tools are usually sculpted by iterative rounds of mutagenesis. In each round, libraries of variants are made and evaluated, and the most promising hits are then retrieved, sequenced, and further characterized. Early efforts to engineer protein-based optical tools were largely manual, suffering from low throughput, human error, and tedium. Here, we describe approaches to automating …

Mechanism Of Ca2+ Transport By Ferroportin, Jiemin Shen, Azaan Saalim Wilbon, Ming Zhou, Yaping Pan

Faculty, Staff and Students Publications

Ferroportin (Fpn) is a transporter that releases ferrous ion (Fe2+) from cells and is important for homeostasis of iron in circulation. Export of one Fe2+ by Fpn is coupled to import of two H+ to maintain charge balance. Here, we show that human Fpn (HsFpn) binds to and mediates Ca2+ transport. We determine the structure of Ca2+-bound HsFpn and identify a single Ca2+ binding site distinct from the Fe2+ binding sites. Further studies validate the Ca2+ binding site and show that Ca2+ transport is not coupled to transport of another ion. In addition, Ca2+ transport is significantly inhibited in the …

Take Your Mother’S Ferry: Preimplantation Embryo Development Requires Maternal Karyopherins For Nuclear Transport, Momal Sharif, Laura Detti, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

The genetic basis of preimplantation embryo arrest is slowly being unraveled. Recent discoveries point to maternally expressed proteins required for cellular functions before the embryonic genome is activated. In this issue of the JCI, Wang, Miyamoto, et al. suggest a critical role for karyopherin-mediated protein cargo transport between oocyte cytoplasm and nucleus. Defective maternal oocyte-expressed human karyopherin subunit α7 (KPNA7) and mouse KPNA2 fail to bind a critical substrate, ribosomal L1 domain-containing protein 1 (RSL1D1), affecting its transport to the nucleus. As shown in embryos of Kpna2-null females, the consequences are disrupted zygotic genome activation and arrest of development. These …

Posoleucel, An Allogeneic, Off-The-Shelf Multivirus-Specific T-Cell Therapy, For The Treatment Of Refractory Viral Infections In The Post-Hct Setting, Thomas Pfeiffer, Ifigeneia Tzannou, Mengfen Wu, Carlos Ramos, Ghadir Sasa, Caridad Martinez, Premal Lulla, Robert A Krance, Lauren Scherer, Daniel Ruderfer, Swati Naik, Claire Bocchini, Iain P Fraser, Badrish Patel, Dany Ward, Tao Wang, Helen E Heslop, Ann M Leen, Bilal Omer

Faculty, Staff and Students Publications

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus.

PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either …

Diagnosis Of Amyotrophic Lateral Sclerosis By Respiratory Function Test, Francesca Polverino, Simone Sampaolo, Antonio Capuozzo, Marco Fasolino, Michele Aliberti, Ersilia Satta, Carlo Santoriello, Mario Polverino

Faculty, Staff and Students Publications

The diagnostic criterion for amyotrophic lateral sclerosis (ALS) based on the findings of concomitant clinical and electrophysiological evidence of upper and lower motor neuron involvement may remain unsatisfied for months and in some patients, even for years in the early stage of the disease. Since respiratory involvement is an onset symptom of ALS in only 1-3% of patients, pulmonary assessment has never been considered useful in the early diagnosis of ALS. However, studies on pulmonary function are lacking, especially in those early stages where neurologic tests are also inconclusive. In contrast to the scarcity of data in the early stages, …

Fifty Years Of A National Program For The Treatment Of Kidney Failure, Kevin F Erickson, Melandrea Worsley, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

No abstract provided.

Total Hip Arthroplasty In The Setting Of Post-Traumatic Arthritis Following Acetabular Fracture: A Systematic Review, Conor S O'Driscoll, Martin S Davey, Andrew J Hughes, John M O'Byrne, Michael Leonard, Brendan J O'Daly

Rothman Institute Papers

Background: Acetabular fractures are frequently associated with post-traumatic arthritis (PTA), for which total hip arthroplasty (THA) has emerged as the established procedure. The purpose of this systematic review is to report the patient outcomes, complications, and implant survival of delayed THA for patients with PTA following acetabular fracture.

Methods: A systematic review was performed in December 2021 as per Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines to identify all studies reporting outcomes of delayed THA performed for PTA with a history of acetabular fracture. From an initial screen of 893 studies, 29 studies which met defined inclusion criteria …

Planarians To Schistosomes: An Overview Of Flatworm Cell-Types And Regulators, J Lee

Faculty, Staff and Student Publications

Schistosomiasis remains a major neglected tropical disease that afflicts over 200 million people globally. Schistosomes, the aetiological agent of schistosomiasis, are parasitic flatworms that propagate between molluscan and mammalian hosts. Inside the mammalian host, schistosomes rapidly grow over 100-fold in size and develop into a sexually mature male or female that thrives in the bloodstream for several decades. Recent work has identified schistosome stem cells as the source that drives parasite transmission, reproduction and longevity. Moreover, studies have begun to uncover molecular programmes deployed by stem cells that are essential for tissue development and maintenance, parasite survival and immune evasion. …

Exploring Therapeutic Strategies For Infantile Neuronal Axonal Dystrophy (Inad/Park14), Guang Lin, Burak Tepe, Geoff Mcgrane, Regine C Tipon, Gist Croft, Leena Panwala, Amanda Hope, Agnes J H Liang, Zhongyuan Zuo, Seul Kee Byeon, Lily Wang, Akhilesh Pandey, Hugo J Bellen

Faculty, Staff and Students Publications

Infantile neuroaxonal dystrophy (INAD) is caused by recessive variants in PLA2G6 and is a lethal pediatric neurodegenerative disorder. Loss of the Drosophila homolog of PLA2G6, leads to ceramide accumulation, lysosome expansion, and mitochondrial defects. Here, we report that retromer function, ceramide metabolism, the endolysosomal pathway, and mitochondrial morphology are affected in INAD patient-derived neurons. We show that in INAD mouse models, the same features are affected in Purkinje cells, arguing that the neuropathological mechanisms are evolutionary conserved and that these features can be used as biomarkers. We tested 20 drugs that target these pathways and found that Ambroxol, Desipramine, …

Validation Of Various Prediction Scores For Cardiac Surgery-Associated Acute Kidney Injury, Anwar Abdullatif Alhulaibi, Abdulrahman Mashatel Alruwaili, Abdullah Saad Alotaibi, ​Fatima Nabih Alshakhs​, Habib Samir Alramadhan, ​Mohammed Salman Koudieh

Journal of the Saudi Heart Association

Background and Objectives: Following cardiac surgery, acute kidney injury (AKI) is a well-known complication that increases morbidity and mortality. This study was carried out to determine the factors associated with acute kidney injury and to assess the predictive value of three predictive scores for the development of AKI post-cardiac surgery in the Saudi community. Methods: In this retrospective study, the medical records of patients aged 18 years and above who underwent cardiac surgery on cardiopulmonary bypass (CPB) at Saud Albabtin Cardiac Center between January 2018 and March 2021 were reviewed. The first stage of both Kidney Disease Improving Global Outcomes …

‘Can You See What I See?’: An Art Project Promoting Living Well With Dementia, Jennifer K. Fortuna

The Open Journal of Occupational Therapy

Caroline Hyland, an illustrator and former occupational therapist based in Dublin, Ireland, provided the cover art for the Winter 2023 edition of The Open Journal of Occupational Therapy (OJOT). “Can You See What I See?” is an acrylic painting on black textured paper. The piece was inspired by Caroline’s grandmother Kathleen Duhig, her love of flowers, and the song “The Dutchman.” Kathleen and three of her sisters lived with dementia. This painting, and several others, are featured in a book Caroline wrote to support living well with dementia. By combining her artistic talents and training as an occupational therapist, Caroline …

Role Of Oxides Of Nitrogen In The Ozone-Cardiorespiratory Visit Association, Xerxes Seposo, Kayo Ueda, Chris Fook Sheng Ng, Lina Madaniyazi, Seiji Sugata, Ayako Yoshino, Akinori Takami

Ateneo School of Medicine and Public Health Publications

Ozone (O3)-induced health effects vary in terms of severity, from deterioration of lung function and hospitalization to death. Several studies have reported a linear increase in health risks after O3 exposure. However, current evidence suggests a non-linear U- and J-shaped concentration-response (C-R) function. The potential increasing risks with decreasing O3 concentrations may seem counterintuitive from the traditional standpoint that decreasing exposure should lead to decreasing health risks. Tus, the question of whether the increasing risks with decreasing concentrations are truly O3-induced or might be from other C-R mechanisms. If these potential risks were not accounted for, this may have contributed …

Enhancing The Quality Of Life For Senior Citizens: A Facilitator’S Guidebook For Mindful Music And Movement, Shannon Sexton

Mindfulness Studies Theses

Music appreciation and enjoyment enhance well-being throughout the lifespan. The challenges and constraints that people experience as they age can lead to lack of access to music, decreased physical activity, and fewer avenues for creative expression. Group music and movement interventions created for older populations offer opportunities for social connection and improved quality of life. Mindful practices add further benefit when combined with these interventions. Current available programs are scarce and most often do not encompass mixed modalities. In addition, the benefits of these programs do not show long-term sustainability. The purpose of this thesis is to explore the effects …

Adar1 Deletion Causes Degeneration Of The Exocrine Pancreas Via Mavs-Dependent Interferon Signaling, Dhwani N Rupani, Fredrik I Thege, Vidhi Chandra, Hajar Rajaei, Robert W Cowan, Sonja M Wörmann, Olivereen Le Roux, Prerna Malaney, Sara L Manning, Jack Hashem, Jennifer Bailey-Lundberg, Andrew D Rhim, Florencia Mcallister

Faculty, Staff and Student Publications

Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional RNA processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role of Adar1 in pancreatic development and homeostasis, we conditionally deleted Adar1 from the murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due to malabsorption associated with exocrine pancreatic insufficiency. Analyses of pancreata revealed ductal cell expansion, heightened interferon-stimulated gene expression and an increased influx of immune cells. Concurrent deletion of Adar1 and Mavs, a …

A Pleiotropic Variant In Dnajb4 Is Associated With Multiple Myeloma Risk, Marco Dicanio, Matteo Giaccherini, Alyssa Clay-Gilmour, Angelica Macauda, Juan Sainz, Mitchell J Machiela, Malwina Rybicka-Ramos, Aaron D Norman, Agata Tyczyńska, Stephen J Chanock, Torben Barington, Shaji K Kumar, Parveen Bhatti, Wendy Cozen, Elizabeth E Brown, Anna Suska, Eva K Haastrup, Robert Z Orlowski, Marek Dudziński, Ramon Garcia-Sanz, Marcin Kruszewski, Joaquin Martinez-Lopez, Katia Beider, Elżbieta Iskierka-Jazdzewska, Matteo Pelosini, Sonja I Berndt, Małgorzata Raźny, Krzysztof Jamroziak, S Vincent Rajkumar, Artur Jurczyszyn, Annette Juul Vangsted, Pilar Garrido Collado, Ulla Vogel, Jonathan N Hofmann, Mario Petrini, Aleksandra Butrym, Susan L Slager, Elad Ziv, Edyta Subocz, Graham G Giles, Niels Frost Andersen, Grzegorz Mazur, Marzena Watek, Fabienne Lesueur, Michelle A T Hildebrandt, Daria Zawirska, Lene Hyldahl Ebbesen, Herlander Marques, Federica Gemignani, Charles Dumontet, Judit Várkonyi, Gabriele Buda, Arnon Nagler, Agnieszka Druzd-Sitek, Xifeng Wu, Katalin Kadar, Nicola J Camp, Norbert Grzasko, Rosalie G Waller, Celine Vachon, Federico Canzian, Daniele Campa

Faculty, Staff and Student Publications

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10-8 ) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10-7 ). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus.

Retrospective Dataset And Survey Analyses Identify Gaps In Data Collection For Craniopharyngioma And Priorities Of Patients And Families Affected By The Disease, Emily Marshall, Nikhil Joshi, Julia Crowley, Shana Mccormack, Sylvia Cheng, Walter Faig, Phillip B Storm, Adam Resnick, Sabine Mueller, Fatema Malbari, Cassie Kline

Department of Medicine Faculty Papers

Introduction: Craniopharyngioma is a rare, low-grade tumor located in the suprasellar region of the brain, near critical structures like the pituitary gland. Here, we concurrently investigate the status of clinical and genomic data in a retrospective craniopharyngioma cohort and survey-based data to better understand patient-relevant outcomes associated with existing therapies and provide a foundation to inform new treatment strategies.

Methods: Clinical, genomic, and outcome data for a retrospective cohort of patients with craniopharyngioma were collected and reviewed through the Children's Brain Tumor Network (CBTN) database. An anonymous survey was distributed to patients and families with a diagnosis of craniopharyngioma to …

Progressive Interstitial Lung Disease In Relatives Of Patients With Pulmonary Fibrosis, Jonathan A Rose, Maria A Planchart Ferretto, Anthony H Maeda, Maria F Perez Garcia, Nikkola E Carmichael, Swati Gulati, Mary B Rice, Hilary J Goldberg, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, Ivan O Rosas, Gary M Hunninghake

Faculty, Staff and Students Publications

No abstract provided.

Routine Pathologic Examination Of The Femoral Head In Total Hip Arthroplasty: A Survey Study Of The American Association Of Hip And Knee Surgeons, Sumon Nandi, Javad Parvizi, Aahks Research Committee

Rothman Institute Papers

Background: Current literature does not provide conclusive evidence on whether routine pathologic examination of femoral heads from total hip arthroplasty is indicated or cost-effective. As a result, there is substantial variation in opinion among surgeons related to this issue. Our study aim was to determine factors that impact surgeon propensity to order pathologic examination of femoral heads.

Methods: A 12-question survey was created to evaluate surgeon practices, indications, and patient care implications surrounding routine pathologic examination of femoral heads. The email survey was distributed to all members of the American Association of Hip and Knee Surgeons (n = 2598).

Results: …

Noninvasive Reflection Spectroscopy Measurement Of Skin Carotenoid Score In Infants Is Feasible And Reliable, Nancy E Moran, Jocelyn Chang, Rachel Stroh, Yusuf Zaidi, Noor Hason, Salma Musaad, Teresia O'Connor

Children’s Nutrition Research Center Staff Publications

Background: Skin carotenoid measurement by reflection spectroscopy (RS) offers a noninvasive biomarker of carotenoid intake, but feasibility, reliability, and validity are not established in infants.

Objectives: In this study we aimed to determine the feasibility and reliability of 4-mo-old infant skin carotenoid score (SCS) measurement and its correlation with total carotenoid intake and plasma concentrations.

Methods: SCSs were measured in a prospective, observational study with a modified, portable RS device at the index finger and heel of the foot in 4-mo-olds (n = 21). Infant plasma, human milk, and formula carotenoid concentrations were measured by HPLC-photodiode array, and carotenoid intake …

A Gain-Of-Function Tpc2 Variant R210c Increases Affinity To Pi(3,5)P2 And Causes Lysosome Acidification And Hypopigmentation, Qiaochu Wang, Zengge Wang, Yizhen Wang, Zhan Qi, Dayong Bai, Chentong Wang, Yuanying Chen, Wenjian Xu, Xili Zhu, Jaepyo Jeon, Jian Xiong, Chanjuan Hao, Michael Xi Zhu, Aihua Wei, Wei Li

Faculty, Staff and Student Publications

Albinism is a group of inherited disorders mainly affecting skin, hair and eyes. Here we identify a de novo point mutation, p.R210C, in the TPCN2 gene which encodes Two Pore Channel 2 (TPC2) from a patient with albinism. TPC2 is an endolysosome and melanosome localized non-selective cation channel involved in regulating pigment production. Through inside-out recording of plasma membrane targeted TPC2 and direct recording of enlarged endolysosomal vacuoles, we reveal that the R210C mutant displays constitutive channel activation and markedly increased affinity to PI(3,5)P2. Mice harboring the homologous mutation, R194C, also exhibit hypopigmentation in the fur and skin, as well …