Medicine and Health Sciences Commons^™

Gene Expression Networks Regulated By Human Personality, Coral Del Val, Elisa Díaz De La Guardia-Bolívar, Igor Zwir, Pashupati P Mishra, Alberto Mesa, Ramiro Salas, Guillermo F Poblete, Gabriel De Erausquin, Emma Raitoharju, Mika Kähönen, Olli Raitakari, Liisa Keltikangas-Järvinen, Terho Lehtimäki, Claude Robert Cloninger

Faculty, Staff and Students Publications

Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic …

Association Of High-Density Lipoprotein Parameters And Risk Of Heart Failure: A Multicohort Analysis, Ambarish Pandey, Kershaw V Patel, Matthew W Segar, Michael D Shapiro, Christie M Ballantyne, Salim S Virani, Vijay Nambi, Erin D Michos, Michael J Blaha, Khurram Nasir, Miguel Cainzos-Achirica, Colby R Ayers, B Daan Westenbrink, Jose L Flores-Guerrero, Stephan J L Bakker, Margery A Connelly, Robin P F Dullaart, Anand Rohatgi

Faculty, Staff and Students Publications

Background: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease.

Objectives: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes.

Methods: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection …

Clinicopathologic Dissociation: Robust Lafora Body Accumulation In Malin Ko Mice Without Observable Changes In Home-Cage Behavior, Vaishnav Krishnan, Jun Wu, Arindam Ghosh Mazumder, Jessica L Kamen, Catharina Schirmer, Nandani Adhyapak, John Samuel Bass, Samuel C Lee, Atul Maheshwari, Gemma Molinaro, Jay R Gibson, Kimberly M Huber, Berge A Minassian

Faculty, Staff and Students Publications

Lafora disease (LD) is a syndrome of progressive myoclonic epilepsy and cumulative neurocognitive deterioration caused by recessively inherited genetic lesions of EPM2A (laforin) or NHLRC1 (malin). Neuropsychiatric symptomatology in LD is thought to be directly downstream of neuronal and astrocytic polyglucosan aggregates, termed Lafora bodies (LBs), which faithfully accumulate in an age-dependent manner in all mouse models of LD. In this study, we applied home-cage monitoring to examine the extent of neurobehavioral deterioration in a model of malin-deficient LD as a means to identify robust preclinical endpoints that may guide the selection of novel genetic treatments. At 6 weeks, ∼6-7 …

Early And Late Complications Of Mandibulectomy Free Flap Reconstruction: Does The Selective Use Of Soft Tissue Only Flaps Reduce Complications?, Dylan B Mcbee, Michael J Dileo, Caroline C Keehn, Andrew T Huang, Angela D Haskins, David J Hernandez

Faculty, Staff and Students Publications

Purpose: This study aims to evaluate the factors most associated with early and late complications following microvascular free tissue transfer (MVFTT) after mandibulectomy.

Methods: A retrospective review of patients undergoing MVFTT after segmental mandibulectomy from September 2016 to February 2021 was performed across a single academic institution. Surgical variables were collected, including the location of the resultant mandibular defect (anterior vs posterior) and flap type (osseous or non-osseous). The primary outcome variables included postoperative complications (early, < 90 days; and late, >90 days) and the patients' functional status (return to oral intake). Descriptive statistics, chi-square test, Fischer's exact test, and 2-sample t tests were used …

Pecarn Prediction Rule For Cervical Spine Imaging Of Children Presenting To The Emergency Department With Blunt Trauma: A Multicentre Prospective Observational Study, Julie C Leonard, Monica Harding, Lawrence J Cook, Jeffrey R Leonard, Kathleen M Adelgais, Fahd A Ahmad, Lorin R Browne, Rebecca K Burger, Pradip P Chaudhari, Daniel J Corwin, Nicolaus W Glomb, Lois K Lee, Sylvia Owusu-Ansah, Lauren C Riney, Alexander J Rogers, Daniel M Rubalcava, Robert E Sapien, Matthew A Szadkowski, Leah Tzimenatos, Caleb E Ward, Kenneth Yen, Nathan Kuppermann

Faculty, Staff and Students Publications

Background: Cervical spine injuries in children are uncommon but potentially devastating; however, indiscriminate neck imaging after trauma unnecessarily exposes children to ionising radiation. The aim of this study was to derive and validate a paediatric clinical prediction rule that can be incorporated into an algorithm to guide radiographic screening for cervical spine injury among children in the emergency department.

Methods: In this prospective observational cohort study, we screened children aged 0-17 years presenting with known or suspected blunt trauma at 18 specialised children's emergency departments in hospitals in the USA affiliated with the Pediatric Emergency Care Applied Research Network (PECARN). …

Optimizing Sexual Reproductive Health Of Men And Women With Cystic Fibrosis: A Systematic Review, Anand G Iyer, Benjamin Yu, Amit Reddy, Mohit Khera

Faculty, Staff and Students Publications

This systematic review summarizes the impact of cystic fibrosis (CF) on sexual and reproductive health (SRH) in males and females, covering pubertal development, hormonal function, family planning, and fertility. Included articles featured historical CF diagnostic criteria, preclinical or clinical data (retrospective cohorts or open label trials), while excluded articles lacked full text availability, explicit methodology, or comparisons between CF and non-CF patients. Genotype differences in CFTR mutations influenced symptom severity. Males with CF experienced delayed puberty, hypogonadism, infertility from obstructive azoospermia, and semen parameter issues. Female CF patients showed decreased fertility, possibly linked to disrupted ionic balance and ovarian cystic …

Utility Of Cystatin C-Based Equation For The Estimation Of Glomerular Filtration Rate In A Pediatric Population, Ridwan B Ibrahim, Poyyapakkam Srivaths, Estella Tam, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations …

Homozygous Missense Variants In Ykt6 Result In Loss Of Function And Are Associated With Developmental Delay, With Or Without Severe Infantile Liver Disease And Risk For Hepatocellular Carcinoma, Mengqi Ma, Mythily Ganapathi, Yiming Zheng, Kai-Li Tan, Oguz Kanca, Kevin E Bove, Norma Quintanilla, Sebnem O Sag, Sehime G Temel, Charles A Leduc, Amanda J Mcpartland, Elaine M Pereira, Yufeng Shen, Jacob Hagen, Christie P Thomas, Nhu Thao Nguyen Galván, Xueyang Pan, Shenzhao Lu, Jill A Rosenfeld, Daniel G Calame, Michael F Wangler, James R Lupski, Davut Pehlivan, Paula M Hertel, Wendy K Chung, Hugo J Bellen

Faculty, Staff and Students Publications

PURPOSE: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases.

METHODS: We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6

RESULTS: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, …

Gender And Emergency Physicians’ Experiences Of Leading Decision Making About Restraint Use: A Qualitative Study, Anita Chary, Beatrice Torres, Elise Brickhouse, Datonye Charles, Ynhi Thomas, Michelle Suh

Faculty, Staff and Students Publications

No abstract provided.

An Electronic Health Record Model For Predicting Risk Of Hepatic Fibrosis In Primary Care Patients, Aaron P Thrift, Theresa H Nguyen Wenker, Kyler Godwin, Maya Balakrishnan, Hao T Duong, Rohit Loomba, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease.

AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes.

METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic …

Genome-Wide Association Study Identifies High-Impact Susceptibility Loci For Hcc In North America, Manal M Hassan, Donghui Li, Younghun Han, Jinyoung Byun, Rikita I Hatia, Erping Long, Jiyeon Choi, Robin Kate Kelley, Sean P Cleary, Anna S Lok, Paige Bracci, Jennifer B Permuth, Roxana Bucur, Jian-Min Yuan, Amit G Singal, Prasun K Jalal, R Mark Ghobrial, Regina M Santella, Yuko Kono, Dimpy P Shah, Mindie H Nguyen, Geoffrey Liu, Neehar D Parikh, Richard Kim, Hui-Chen Wu, Hashem El-Serag, Ping Chang, Yanan Li, Yun Shin Chun, Sunyoung S Lee, Jian Gu, Ernest Hawk, Ryan Sun, Chad Huff, Asif Rashid, Hesham M Amin, Laura Beretta, Robert A Wolff, Samuel O Antwi, Yehuda Patt, Lu-Yu Hwang, Alison P Klein, Karen Zhang, Mikayla A Schmidt, Donna L White, John A Goss, Saira A Khaderi, Jorge A Marrero, Francisco G Cigarroa, Pankil K Shah, Ahmed O Kaseb, Lewis R Roberts, Christopher I Amos

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP).

APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a …

Depressive Symptoms Are Associated With C-Reactive Protein In Older Adults With Obesity, Henry D Heisey, Clifford Qualls, Dennis T Villareal, Martha Belen Segoviano-Escobar, Maria Liza Duremdes Nava, Jennifer R Gatchel, Mark E Kunik

Faculty, Staff and Students Publications

OBJECTIVES: To test the hypothesis that depressive symptoms vary with high-sensitivity C-reactive protein (hs-CRP), among older adults with obesity.

METHODS: This was a cross-sectional, secondary analysis of baseline data from two related lifestyle intervention trials. The study sample comprises 148 consecutively recruited, community-dwelling older adults (age >=65 years) without severe psychiatric illness and with body mass index >=30 kg/m

RESULTS: Sample mean GDS score was 2.7 (SD 3.0, range 0 - 14). A significant multivariate model of GDS scores (R

CONCLUSIONS: In older adults with obese BMI, male sex and higher hs-CRP are associated with depression, even in a group …

The Road To Tailored Adjuvant Chemotherapy For All Four Non-Pancreatic Periampullary Cancers: An International Multimethod Cohort Study, Bas A Uijterwijk, Daniël H Lemmers, Michele Ghidini, Johanna W Wilmink, Alberto Zaniboni, Giuseppe Kito Fusai, Alessandro Zerbi, Bas Groot Koerkamp, Misha Luyer, Poya Ghorbani, Roberto Salvia, Steven White, Benedetto Ielpo, Brian K P Goh, Ugo Boggi, Geert Kazemier, Michael G House, Vasileios K Mavroeidis, Bergthor Björnsson, Michele Mazzola, Mario Serradilla, Dimitris Korkolis, Adnan Alseidi, Keith J Roberts, Zahir Soonawalla, Patrick Pessaux, William E Fisher, Sharnice Koek, Tara S Kent, Miljana Vladimirov, Louisa Bolm, Nigel Jamieson, Raffaele Dalla Valle, Jorg Kleeff, Alessandro Mazzotta, Miguel Angel Suarez Muñoz, Santiago Sánchez Cabús, Chad G Ball, Adam C Berger, Clarissa Ferarri, Marc G Besselink, Mohammed Abu Hilal, International Study Group On Non-Pancreatic Periampullary Cancer (Isgaca)

Center for Medical Ethics and Health Policy Staff Publications

Background: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB.

Patients and methods: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens …

Nfatc1 Is Required For Vitamin D- And Phosphate-Mediated Regulation Of Osteocyte Lacuno-Canalicular Remodeling, Supriya Jagga, Ashleigh Hughes, Niusha Manoochehri Arash, Melissa Sorsby, Daniel J Brooks, Paola Divieti Pajevic, Eva S Liu

Staff and Researcher Publications

Osteocytes are embedded in lacunae and connected by canaliculi (lacuno-canalicular network, LCN). Bones from mice with X-linked hypophosphatemia (Hyp), which have impaired production of 1,25 dihydroxyvitamin D (1,25D) and hypophosphatemia, have abnormal LCN structure that is improved by treatment with 1,25D or an anti-FGF23 targeting antibody, supporting roles for 1,25D and phosphate in regulating LCN remodeling. Bones from mice lacking the vitamin D receptor (VDR) in osteocytes (Vdrf/f;Dmp1Cre+) and mice lacking the sodium phosphate transporter 2a (Npt2aKO), which have low serum phosphate with high serum 1,25D, have impaired LCN organization, demonstrating that osteocyte-specific actions of 1,25D and hypophosphatemia regulate LCN …

Thrombosis Risk Prediction In Lymphoma Patients: A Multi-Institutional, Retrospective Model Development And Validation Study, Shengling Ma, Jennifer La, Kaitlin N Swinnerton, Danielle Guffey, Raka Bandyo, Giordana De Las Pozas, Katy Hanzelka, Xiangjun Xiao, Cristhiam M Rojas-Hernandez, Christopher I Amos, Vipul Chitalia, Katya Ravid, Kelly W Merriman, Christopher R Flowers, Nathanael Fillmore, Ang Li

Faculty, Staff and Students Publications

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the …

A Klf2-Bmper-Smad1/5 Checkpoint Regulates High Fluid Shear Stress-Mediated Artery Remodeling, Hanqiang Deng, Jiasheng Zhang, Yewei Wang, Divyesh Joshi, Xinchun Pi, Sarah De Val, Martin A Schwartz

Faculty, Staff and Students Publications

Vascular remodeling to match arterial diameter to tissue requirements commonly fails in ischemic disease. Endothelial cells sense fluid shear stress (FSS) from blood flow to maintain FSS within a narrow range in healthy vessels. Thus, high FSS induces vessel outward remodeling, but mechanisms are poorly understood. We previously reported that Smad1/5 is maximally activated at physiological FSS. Smad1/5 limits Akt activation, suggesting that inhibiting Smad1/5 may facilitate outward remodeling. Here we report that high FSS suppresses Smad1/5 by elevating KLF2, which induces the bone morphogenetic protein (BMP) pathway inhibitor, BMP-binding endothelial regulator (BMPER), thereby de-inhibiting Akt. In mice, surgically induced …

Trans-Ancestral Genetic Risk Factors For Treatment-Related Type 2 Diabetes Mellitus In Survivors Of Childhood Cancer, Cindy Im, Achal Neupane, Jessica L Baedke, Brian Lenny, Angela Delaney, Stephanie B Dixon, Eric J Chow, Sogol Mostoufi-Moab, Tianzhong Yang, Melissa A Richard, M Monica Gramatges, Philip J Lupo, Noha Sharafeldin, Smita Bhatia, Gregory T Armstrong, Melissa M Hudson, Kirsten K Ness, Leslie L Robison, Yutaka Yasui, Carmen L Wilson, Yadav Sapkota

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D.

Patients and methods: Leveraging whole-genome sequencing data from the St Jude Lifetime Cohort (N = 3,676, 304 clinically ascertained cases), we conducted ancestry-specific genome-wide association studies among survivors of African and European genetic ancestry (AFR and EUR, respectively) followed by trans-ancestry meta-analysis. Trans-/within-ancestry replication including data from the Childhood Cancer Survivor Study (N = 5,965) was required for prioritization. Three external general population T2D polygenic …

The Role Of Transoral Incisionless Fundoplication (Tif) In The Management Of Gastroesophageal Reflux Disease (Gerd) Following Peroral Endoscopic Myotomy (Poem): A Pilot, Prospective, Patient-Driven Study, Fares Ayoub, Tara Keihanian, Noor Zabad, Salmaan Jawaid, Kalpesh Patel, Mohamed O Othman

Faculty, Staff and Students Publications

BACKGROUND: Gastroesophageal reflux (GERD) is a concern after peroral endoscopic myotomy (POEM). Transoral incisionless fundoplication (TIF) has been recently described as a possible therapy for post-POEM GERD in case series.

METHODS: We prospectively enrolled patients undergoing POEM who agreed to participate in objective post-procedure GERD evaluation. Patients with objective evidence of GERD and suitable anatomy were offered TIF vs. proton pump inhibitor (PPI) only. Patients who underwent TIF were compared to those on PPI-only therapy after follow-up.

RESULTS: Of 21 enrolled POEM patients with objective testing, GERD was found in 11 (52%). Of those eligible for TIF, 4 (40%) opted …

First-In-Human Hyperpolarized Mri For Tumor Metabolism In Hnscc, Stephen Y Lai, Vlad C Sandulache, Dawid Schellingerhout, Clifton D Fuller, Yunyun Chen, Christopher M Walker, James A Bankson

Faculty, Staff and Student Publications

This case report describes the use of hyperpolarized magnetic resonance imaging (MRI) in a patient with head and neck squamous cell carcinoma (HNSCC) to demonstrate its translational viability.

Exome Sequencing Identifies Novel Genes Underlying Primary Congenital Glaucoma In The National Birth Defects Prevention Study, Elizabeth E Blue, Kristin J Moore, Kari E North, Tania A Desrosiers, Suzan L Carmichael, Janson J White, Jessica X Chong, Michael J Bamshad, Mary M Jenkins, Lynn M Almli, Lawrence C Brody, Sharon F Freedman, Jennita Reefhuis, Paul A Romitti, Gary M Shaw, Martha Werler, Denise M Kay, Marilyn L Browne, Marcia L Feldkamp, Richard H Finnell, Wendy N Nembhard, Faith Pangilinan, Andrew F Olshan, National Institutes Of Health Intramural Sequencing Center, University Of Washington Center For Mendelian Genomics, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

Background: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants.

Methods: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention …

Integrating Multisector Molecular Characterization Into Personalized Peptide Vaccine Design For Patients With Newly Diagnosed Glioblastoma, Tanner M Johanns, Elizabeth A R Garfinkle, Katherine E Miller, Alexandra J Livingstone, Kaleigh F Roberts, Lakshmi P Rao Venkata, Joshua L Dowling, Michael R Chicoine, Ralph G Dacey, Gregory J Zipfel, Albert H Kim, Elaine R Mardis, Gavin P Dunn

2020-Current year OA Pubs

PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax.

PATIENTS AND METHODS: In this …

Epigenetic Developmental Mechanisms Underlying Sex Differences In Cancer, Joshua B. Rubin, Tamara Abou-Antoun, Joseph E. Ippolito, Lorida Llaci, Camryn T. Marquez, Jason P. Wong, Lihua Yang

2020-Current year OA Pubs

Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, …

Tumor-Immune Signatures Of Treatment Resistance To Brentuximab Vedotin With Ipilimumab And/Or Nivolumab In Hodgkin Lymphoma, Edgar Gonzalez-Kozlova, Brad S Kahl, Et Al.

2020-Current year OA Pubs

UNLABELLED: To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed …

Suicide In Us Preteens Aged 8 To 12 Years, 2001 To 2022, Donna A Ruch, Lisa M Horowitz, Jennifer L Hughes, Katherine Sarkisian, Joan L Luby, Cynthia A Fontanella, Jeffrey A Bridge

2020-Current year OA Pubs

No abstract provided.

Matching-Adjusted Indirect Comparison From The Lymphoma Epidemiology Of Outcomes Consortium For Real World Evidence (Leo Crewe) Study To A Clinical Trial Of Mosunetuzumab In Relapsed Or Refractory Follicular Lymphoma, Matthew J. Maurer, Brad S. Kahl, Et Al.

2020-Current year OA Pubs

Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate (ORR) of 80%, complete response (CR) rate of 60%, and a median progression-free survival (PFS) of 17.9 months in patients with relapsed/refractory (R/R) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for R/R FL can provide some context …

[18f]F-Arag Imaging Reveals Association Between Neuroinflammation And Brown- And Bone Marrow Adipose Tissue, Jelena Levi, Caroline Guglielmetti, Et Al.

2020-Current year OA Pubs

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [

Momelotinib Vs. Ruxolitinib In Myelofibrosis Patient Subgroups By Baseline Hemoglobin Levels In The Simplify-1 Trial, Vikas Gupta, Stephen Oh, Et Al.

2020-Current year OA Pubs

A key hallmark of myelofibrosis is anemia, which ranges from mild to severe based on hemoglobin levels. To more clearly define outcomes with the Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib by anemia severity, we performed a descriptive post hoc exploratory analysis of the double-blind, randomized, phase 3 SIMPLIFY-1 study (NCT01969838;

Distinguishing Recrudescence From Reinfection In Lymphatic Filariasis, Young-Jun Choi, Kerstin Fischer, Aboulaye Méité, Benjamin G Koudou, Peter U Fischer, Makedonka Mitreva

2020-Current year OA Pubs

BACKGROUND: The Global Program to Eliminate Lymphatic Filariasis (GPELF) is the largest public health program based on mass drug administration (MDA). Despite decades of MDA, ongoing transmission in some countries remains a challenge. To optimise interventions, it is critical to differentiate between recrudescence and new infections. Since adult filariae are inaccessible in humans, deriving a method that relies on the offspring microfilariae (mf) is necessary.

METHODS: We developed a genome amplification and kinship analysis-based approach using Brugia malayi samples from gerbils, and applied it to analyse Wuchereria bancrofti mf from humans in Côte d'Ivoire. We examined the pre-treatment genetic diversity …

Diagnostic Efficacy And Clinical Impact Of Image-Guided Core Needle Biopsy Of Suspected Vertebral Osteomyelitis, Winston L Winkler, Ige A George, Sumanth Gandra, Jonathan C Baker, Anderanik Tomasian, Benjamin Northrup, Theodore L Vander Velde, Travis J Hillen, Chongliang Luo, Resten Imaoka, Gino M Dettorre, Jack W Jennings

2020-Current year OA Pubs

OBJECTIVES: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected vertebral osteomyelitis in adults is heterogenous in published studies owing to small sample sizes, indicating the need for large cohort studies.

METHODS: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with imaging findings consistent with vertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. In addition, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. A multivariate statistical analysis …

Plasmacytoid Dendritic Cells Control Homeostasis Of Megakaryopoiesis, Florian Gaertner, Marco Colonna, Et Al.

2020-Current year OA Pubs

Platelet homeostasis is essential for vascular integrity and immune defence