Medicine and Health Sciences Commons^™

Preclinical Studies In Krabbe Disease: A Model For The Investigation Of Novel Combination Therapies For Lysosomal Storage Diseases, Gregory Heller, Allison M Bradbury, Mark S Sands, Ernesto R Bongarzone

2020-Current year OA Pubs

Krabbe disease (KD) is a lysosomal storage disease (LSD) caused by mutations in the galc gene. There are over 50 monogenetic LSDs, which largely impede the normal development of children and often lead to premature death. At present, there are no cures for LSDs and the available treatments are generally insufficient, short acting, and not without co-morbidities or long-term side effects. The last 30 years have seen significant advances in our understanding of LSD pathology as well as treatment options. Two gene therapy-based clinical trials, NCT04693598 and NCT04771416, for KD were recently started based on those advances. This review will …

Magnify Is A Universal Molecular Anchoring Strategy For Expansion Microscopy, Aleksandra Klimas, Brendan R Gallagher, Piyumi Wijesekara, Sinda Fekir, Emma F Dibernardo, Zhangyu Cheng, Donna B Stolz, Franca Cambi, Simon C Watkins, Steven L Brody, Amjad Horani, Alison L Barth, Christopher I Moore, Xi Ren, Yongxin Zhao

2020-Current year OA Pubs

Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols require prior treatment with reactive anchoring chemicals to link specific labels and biomolecule classes to the gel. We describe a strategy called Magnify, which uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids without the need for a separate anchoring step. Magnify expands biological specimens up to 11 times and facilitates imaging of cells and tissues with effectively around 25-nm resolution using a diffraction-limited objective lens of about 280 nm on conventional …

Hydrogen Deuterium Exchange And Other Mass Spectrometry-Based Approaches For Epitope Mapping, Prashant N Jethva, Michael L Gross

2020-Current year OA Pubs

Antigen-antibody interactions are a fundamental subset of protein-protein interactions responsible for the "survival of the fittest". Determining the interacting interface of the antigen, called an epitope, and that on the antibody, called a paratope, is crucial to antibody development. Because each antigen presents multiple epitopes (unique footprints), sophisticated approaches are required to determine the target region for a given antibody. Although X-ray crystallography, Cryo-EM, and nuclear magnetic resonance can provide atomic details of an epitope, they are often laborious, poor in throughput, and insensitive. Mass spectrometry-based approaches offer rapid turnaround, intermediate structural resolution, and virtually no size limit for the …

Assessment Of Antibodies In The Upper And Lower Human Respiratory Tract At Steady State And After Respiratory Viral Infection, Marios Koutsakos, Jackson S Turner, M Cristina Vazquez Guillamet, Daniel Reynolds, Tingting Lei, Derek E Byers, Ali H Ellebedy, Philip A Mudd

2020-Current year OA Pubs

OBJECTIVES: There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings.

METHODS: We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were …

Aberrant T-Cell Exhaustion In Severe Combined Immunodeficiency Survivors With Poor T-Cell Reconstitution After Transplantation, Roxane Labrosse, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

BACKGROUND: Severe combined immunodeficiency (SCID) comprises rare inherited disorders of immunity that require definitive treatment through hematopoietic cell transplantation (HCT) or gene therapy for survival. Despite successes of allogeneic HCT, many SCID patients experience incomplete immune reconstitution, persistent T-cell lymphopenia, and poor long-term outcomes.

OBJECTIVE: We hypothesized that CD4

METHODS: We analyzed markers of exhaustion in blood samples from 61 SCID patients at a median of 10.4 years after HCT.

RESULTS: Compared to post-HCT SCID patients with normal CD4

CONCLUSIONS: Recipients of unconditioned HCT for SCID may develop late post-HCT T-cell exhaustion as a result of diminished production of T-lineage …

Necrotic Cardiac Myocytes Skew Macrophage Polarization Towards A Classically Activated Phenotype, Wenlong Jiang, Luigi Adamo, Kenji Lim, Scot J Matkovich, Sarah Evans, Cibele Rocha-Resende, Douglas L. Mann

2020-Current year OA Pubs

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide …

#Orthotwitter: Relationship Between Author Twitter Utilization And Academic Impact In Orthopaedic Surgery, Ryan T Halvorson, Sachin Allahabadi, Nicolas Cevallos, Aidan J. Foley, Kelsey Collins, Abel Torres Espin, Brian T. Feeley, Nirav K. Pandya, Jeannie F. Bailey

2020-Current year OA Pubs

Background #OrthoTwitter has evolved to disseminate findings and engage the public. However, the academic impact of Twitter utilization in orthopaedic surgery is unknown. Questions/purposes The purpose of the study was to evaluate relationships between the author and manuscript Twitter activity and citations. Methods Manuscripts in 17 orthopaedic journals from 2018 were identified. Citations, online mentions, impact factors, and subspecialties were obtained. H-index and Twitter account details for authors were obtained for a subset of manuscripts. Relationships between Twitter activity and citations were evaluated. Results 2,473/4,224 (58.5%) manuscripts were mentioned on Twitter (n=29,958 mentions), with Twitter manuscripts cited more frequently (median …

Testing Of A Novel Questionnaire Of Household Exposure To Wood Smoke, Paula M. Meek, Sarah J. Schmiege, Akshay Sood, Hans Petersen, Rodrigo Vazquez-Guillamet, Hammad Irshad, Jacob Mcdonald, Yohannes Tesfaigzi

2020-Current year OA Pubs

Household air pollution from wood smoke (WS), contributes to adverse health effects in both low- and high-income countries. However, measurement of WS exposure has been limited to expensive in-home monitoring and lengthy face-to-face interviews. This paper reports on the development and testing of a novel, self-report nine-item measure of WS exposure, called the Household Exposure to Wood Smoke (HEWS). A sample of 149 individuals using household wood stoves for heating from western states in the U.S., completed the HEWS during the winter months (November to March) of 2013 through 2016 with 30 subjects having in-home particle monitoring. Hard copy or …

Innovations In Hematopoietic Stem-Cell Mobilization: A Review Of The Novel Cxcr4 Inhibitor Motixafortide, Zachary D. Crees, Michael P. Rettig, John F. Dipersio

2020-Current year OA Pubs

Hematopoietic stem-cell transplantation (HCT) and stem-cell-based gene therapies rely on the ability to collect sufficient CD34+ hematopoietic stem and progenitor cells (HSPCs), typically

Open-Source Statistical And Data Processing Tools For Wide-Field Optical Imaging Data In Mice, Lindsey M. Brier, Joseph P. Culver

2020-Current year OA Pubs

SIGNIFICANCE: Wide-field optical imaging (WOI) can produce concurrent hemodynamic and cell-specific calcium recordings across the entire cerebral cortex in animal models. There have been multiple studies using WOI to image mouse models with various environmental or genetic manipulations to understand various diseases. Despite the utility of pursuing mouse WOI alongside human functional magnetic resonance imaging (fMRI), and the multitude of analysis toolboxes in the fMRI literature, there is not an available open-source, user-friendly data processing and statistical analysis toolbox for WOI data.

AIM: To assemble a MATLAB toolbox for processing WOI data, as described and adapted to combine techniques from …

Study Protocol: A Cross-Sectional Survey Of Clinicians To Identify Barriers To Clinical Practice Guideline Implementation In The Assessment And Treatment Of Persistent Tic Disorders, Jaclyn M. Martindale, Harini Sarva, Davide Martino, Donald L. Gilbert, Christos Ganos, Tamara Pringsheim, Kevin J. Black, Irene A. Malaty

2020-Current year OA Pubs

INTRODUCTION: Eight members of the International Parkinson's Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation. Based on expert opinion and literature review, the consensus was that practice variations continue to be quite broad and that many barriers in different clinical settings might negatively influence the adoption of the American Academy of Neurology and the European Society for the Study of Tourette Syndrome published guidelines.

OBJECTIVES: 1) To identify how clinical practices diverge from the existing American Academy of Neurology and European Society for the Study of …

Adherence To And Experiences Of K-12 Students In Modified And Standard Home Quarantine During The Sars-Cov-2 Pandemic In Missouri, Mary Claire Worrell, Sara Malone, Patrick Dawson, Stephanie A. Fritz, Ebony Thomas, Bre Peeler, Catherine Rains, Sarah C. Tinker, John C. Neatherlin, Lisa Barrios, Jon Mooney, Katie Towns, Jason Newland, Johanna S. Salzer

2020-Current year OA Pubs

BACKGROUND: In November 2020, during the SARS-CoV-2 pandemic, Missouri allowed local public health jurisdictions the option to implement a modified quarantine policy allowing kindergarten through 12 (K-12) students with low-risk exposures to continue in-person learning. We assessed adherence to quarantine among participants in modified quarantine and standard home quarantine and the psychosocial impacts of quarantine on students and families.

METHODS: In January-March 2021, as part of an investigation of in-school transmission of SARS-CoV-2, parents of 586 participating K-12 students identified as a close contact with a person with SARS-CoV-2 were sent a survey to assess their activities and psychosocial impacts …

X-Ray And Mr Contrast Bearing Nanoparticles Enhance The Therapeutic Response Of Image-Guided Radiation Therapy For Oral Cancer, Gayatri Sharma, Mir Hadi Razeghi Kondelaji, Guru P. Sharma, Christopher Hansen, Abdul K. Parchur, Shayan Shafiee, Jaidip M. Jagtap, Brian Fish, Carmen Bergom, Eric Paulson, William A. Hall, Heather A. Himburg, Amit Joshi

2020-Current year OA Pubs

INTRODUCTION: Radiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models.

METHODS: PEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery. The radiation therapy enhancement mechanism was investigated.

RESULTS: Theranostic nanoparticles demonstrated both X-ray/magnetic resonance contrast in a …

Evaluation Of A Large-Scale Health Department Naloxone Distribution Program: Per Capita Naloxone Distribution And Overdose Morality, Caroline E. Freiermuth, Rachel M. Ancona, Jennifer L. Brown, Brittany E. Punches, Shawn A. Ryan, Tim Ingram, Michael S. Lyons

2020-Current year OA Pubs

OBJECTIVES: To report per-capita distribution of take-home naloxone to lay bystanders and evaluate changes in opioid overdose mortality in the county over time.

METHODS: Hamilton County Public Health in southwestern Ohio led the program from Oct 2017-Dec 2019. Analyses included all cartons distributed within Hamilton County or in surrounding counties to people who reported a home address within Hamilton County. Per capita distribution was estimated using publicly available census data. Opioid overdose mortality was compared between the period before (Oct 2015-Sep 2017) and during (Oct 2017-Sep 2019) the program.

RESULTS: A total of 10,416 cartons were included for analyses, with …

The Rate And Predictors Of Healing Of Repaired Lesser Tuberosity Osteotomy In Reverse Total Shoulder Arthroplasty, Benjamin Zmistowski, Sean V Cahill, J Ryan Hill, Joseph T Gibian, Ruba Sokrab, Jay D Keener, Alexander W Aleem

2020-Current year OA Pubs

BACKGROUND: Evidence is building that a functional subscapularis improves function-specifically internal rotation tasks-following reverse total shoulder arthroplasty (rTSA). However, the optimal method for subscapularis repair during rTSA remains unknown with variable healing rates reported. This study aims to investigate the rate of and predictors for healing a lesser tuberosity osteotomy (LTO) following rTSA.

METHODS: Following local institutional review board approval, patients with at least one-year follow-up for rTSA managed with an LTO and subsequent repair between March, 2017 and March, 2020 were retrospectively identified. Shoulders were selected for LTO repair based upon preoperative imaging and intraoperative assessment of subscapularis quality. …

Genetic Variation In Environmental Enteropathy And Stunting In Zambian Children: A Pilot Genome Wide Association Study Using The H3africa Chip, Monica N. Mweetwa, Talin Haritunians, Shishir Dube, Kanta Chandwe, Beatrice Amadi, Kanekwa Zyambo, Ta-Chiang Liu, Dermot Mcgovern, Paul Kelly

2020-Current year OA Pubs

PURPOSE: Stunting is known to be heavily influenced by environmental factors, so the genetic contribution has received little attention. Here we report an exploration of genetic influences in stunted Zambian children with environmental enteropathy.

METHOD: Children with stunting (LAZ < -2) were enrolled and given nutritional therapy. Those that were non-responsive to therapy were designated as cases, and children with good growth (LAZ > -1) from the same community as controls. Blood and stool samples were taken to measure biomarkers of intestinal inflammation, epithelial damage, and microbial translocation. Single nucleotide polymorphism array genotyping was carried out on saliva samples using the H3Africa consortium array.

RESULTS: Genome wide associations were analysed in 117 cases and 41 controls. While no significant associations with stunting were observed at …

Supplementary Feeding And Infection Control In Pregnant Adolescents-A Secondary Analysis Of A Randomized Trial Among Malnourished Women In Sierra Leone, Aminata S Koroma, Mariama Ellie, Kadiatu Bangura, Per O Iversen, David T Hendrixson, Kevin Stephenson, Mark J Manary

2020-Current year OA Pubs

Undernutrition during pregnancy in adolescence confers a high risk of maternal morbidity and adverse birth outcomes, particularly in low-resource settings. In a secondary analysis, we hypothesized that younger undernourished pregnant adolescents (<18 years) would benefit more than undernourished pregnant adults (>20 years) from the intervention of supplementary food and anti-infective treatments. The original trial in Sierra Leone enrolled 236 younger adolescents (<18 years), 454 older adolescents (aged 18-19 years), and 741 adults (≥20 years), all with a mid-upper arm circumference ≤23 cm. Younger adolescents had lower final fundal height as well as smaller newborns (-0.3 kg; 95% confidence interval [CI], -0.3, -0.2; p < 0.001) and shorter newborns (-1.1 cm; 95% CI, -1.5, -0.7; p < 0.001) than adults. The intervention's effect varied significantly between maternal age groups: adults benefited more than younger adolescents with respect to newborn birth weight (difference in difference, 166 g; 95% CI, 26, 306; interaction p = 0.02), birth length (difference in difference, 7.4 mm; 95% CI, 0.1, 14.8; interaction p = 0.047), and risk for low birth weight (<2.5 kg) (interaction p = 0.019). The differences in response persisted despite adjustments for maternal anthropometry, the number of prior pregnancies, and human immunodeficiency virus status. Older adolescents similarly benefited more than younger adolescents, though differences did not reach statistical significance. In conclusion, newborns born to younger adolescent mothers had worse outcomes than those born to adult mothers, and adults and their newborns benefited more from the intervention than younger adolescents.

Sting Suppresses Mitochondrial Vdac2 To Govern Rcc Growth Independent Of Innate Immunity, Zhichuan Zhu, Xin Zhou, Hongwei Du, Erica W Cloer, Jiaming Zhang, Liu Mei, Ying Wang, Xianming Tan, Austin J Hepperla, Jeremy M Simon, Jeanette Gowen Cook, Michael B Major, Gianpietro Dotti, Pengda Liu

2020-Current year OA Pubs

STING is an innate immune sensor for immune surveillance of viral/bacterial infection and maintenance of an immune-friendly microenvironment to prevent tumorigenesis. However, if and how STING exerts innate immunity-independent function remains elusive. Here, the authors report that STING expression is increased in renal cell carcinoma (RCC) patients and governs tumor growth through non-canonical innate immune signaling involving mitochondrial ROS maintenance and calcium homeostasis. Mitochondrial voltage-dependent anion channel VDAC2 is identified as a new STING binding partner. STING depletion potentiates VDAC2/GRP75-mediated MERC (mitochondria-ER contact) formation to increase mitochondrial ROS/calcium levels, impairs mitochondria function, and suppresses mTORC1/S6K signaling leading to RCC growth …

Slc-0111, An Inhibitor Of Carbonic Anhydrase Ix, Attenuates Hepatoblastoma Cell Viability And Migration, Katja Eloranta, Marjut Pihlajoki, Emmi Liljeström, Ruth Nousiainen, Tea Soini, Jouko Lohi, Stefano Cairo, David B Wilson, Seppo Parkkila, Markku Heikinheimo

2020-Current year OA Pubs

BACKGROUND: In response to hypoxia, tumor cells undergo transcriptional reprogramming including upregulation of carbonic anhydrase (CA) IX, a metalloenzyme that maintains acid-base balance. CAIX overexpression has been shown to correlate with poor prognosis in various cancers, but the role of this CA isoform in hepatoblastoma (HB) has not been examined.

METHODS: We surveyed the expression of CAIX in HB specimens and assessed the impact of SLC-0111, a CAIX inhibitor, on cultured HB cells in normoxic and hypoxic conditions.

RESULTS: CAIX immunoreactivity was detected in 15 out of 21 archival pathology HB specimens. The CAIX-positive cells clustered in the middle of …

Updates In The Chronic Kidney Disease-Mineral Bone Disorder Show The Role Of Osteocytic Proteins, A Potential Mechanism Of The Bone-Vascular Paradox, A Therapeutic Target, And A Biomarker, Matthew J Williams, Sarah C White, Zachary Joseph, Keith A Hruska

2020-Current year OA Pubs

The chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex multi-component syndrome occurring during kidney disease and its progression. Here, we update progress in the components of the syndrome, and synthesize recent investigations, which suggest a potential mechanism of the bone-vascular paradox. The discovery that calcified arteries in chronic kidney disease inhibit bone remodeling lead to the identification of factors produced by the vasculature that inhibit the skeleton, thus providing a potential explanation for the bone-vascular paradox. Among the factors produced by calcifying arteries, sclerostin secretion is especially enlightening. Sclerostin is a potent inhibitor of bone remodeling and an osteocyte …

Oral Low-Dose Naltrexone In The Treatment Of Grontal Fibrosing Alopecia And Lichen Planopilaris: An Uncontrolled Open-Label Prospective Study, Remi K. Hamel, Ling Chen, Cailin O'Connell, Caroline Mann

2020-Current year OA Pubs

Background Frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) is scarring alopecias with limited evidence supporting their treatment options. We investigated the use of low-dose naltrexone (3 mg oral daily) as adjunctive therapy in the treatment of FFA and LPP. Methods A single-center, uncontrolled open-label prospective study was performed, with 26 patients who took low-dose naltrexone for one year included in the per-protocol analysis. Both patient-reported (pruritus and burning/pain) and physician-assessed (erythema, scale, and scalp involvement) outcomes were analyzed. Results There were decreases in erythema and scale for the overall longitudinal outcomes using linear mixed effects model analysis. However, only …

Sex-Related Differences In Premature Cardiovascular Disease In Familial Hypercholesterolemia, Anandita Agarwala, Elena Deych, Laney K Jones, Amy C Sturm, Karen Aspry, Zahid Ahmad, Christie M Ballantyne, Anne C Goldberg

2020-Current year OA Pubs

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors.

OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH.

METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and …

An Analysis Of Major Target Deviations In Craniospinal Irradiation Treatment Plans For Patients With Intermediate-Risk Medulloblastoma Within A Phase 3 Clinical Trial (Children's Oncology Group Study Acns0331), Joshua P Schiff, Yimei Lee, Yu Wang, Stephanie M Perkins, Sandy K Kessel, Thomas J Fitzgerald, Nicole A Larrier, Jeff M Michalski

2020-Current year OA Pubs

PURPOSE: Craniospinal irradiation remains an essential and yet difficult part of the treatment of patients with medulloblastoma. Whereas technological advances offer promise of increased conformity, realiance on advanced technology is not without risk, and it remains critical to carefully delineate targets. We describe examples of target deviations (TDs) in craniospinal irradiation treatment plans for postoperative patients with medulloblastoma in a phase 3 clinical trial (ACNS 0331).

METHODS AND MATERIALS: The principal investigator independently performed a review of the treatment plans and portal films of enrolled patients and evaluated the plans for TDs. TDs of dose, dose uniformity, and volume were …

Nonalcoholic Fatty Liver Disease Is A Risk Factor For Thiopurine Hepatotoxicity In Crohn's Disease, Alvin T George, Matthew Glover, Quazim Alayo, Maria Zulfiqar, Daniel R Ludwig, Matthew A Ciorba, Scott Mchenry, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

METHODS: In this prospective cohort analysis, CD patients at a single center were recruited 6/2017-5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a …

Efficacy Of Laser Interstitial Thermal Therapy For Biopsy-Proven Radiation Necrosis In Radiographically Recurrent Brain Metastases, Michael Chan, Albert H Kim, Eric Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.

METHODS: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.

RESULTS: Ninety patients met …

How Penalizing Substance Use In Pregnancy Affects Treatment And Research: A Qualitative Examination Of Researchers' Perspectives, Seema K Shah, Leishla Perez-Cardona, Khrystyna Helner, Suena H Massey, Ashish Premkumar, Renee Edwards, Elizabeth S Norton, Cynthia E Rogers, Emily S Miller, Christopher D Smyser, Matthew M Davis, Lauren S Wakschlag

2020-Current year OA Pubs

INTRODUCTION: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood.

METHODS: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis.

RESULTS: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal …

Multi-Omic Analysis Of The Tumor Microenvironment Shows Clinical Correlations In Ph1 Study Of Atezolizumab +/- Soc In Mm, Sandy Wong, Habib Hamidi, Luciano J Costa, Selma Bekri, Natalia Neparidze, Ravi Vij, Tina G Nielsen, Aparna Raval, Rajan Sareen, Elisabeth Wassner-Fritsch, Hearn J Cho

2020-Current year OA Pubs

Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel …

Neurobridge: A Prototype Platform For Discovery Of The Long-Tail Neuroimaging Data, Lei Wang, Janine Bijsterbosch, Rick Herrick, Daniel Marcus, Stephen M Moore, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Open science initiatives have enabled sharing of large amounts of already collected data. However, significant gaps remain regarding how to find appropriate data, including underutilized data that exist in the long tail of science. We demonstrate the NeuroBridge prototype and its ability to search PubMed Central full-text papers for information relevant to neuroimaging data collected from schizophrenia and addiction studies.

METHODS: The NeuroBridge architecture contained the following components: (1) Extensible ontology for modeling study metadata: subject population, imaging techniques, and relevant behavioral, cognitive, or clinical data. Details are described in the companion paper in this special issue; (2) A …

Critcom: Assessment Of Quality Of Interdisciplinary Communication Around Deterioration In Pediatric Oncologic Patients, Jocelyn Rivera, Sara Malone, Kim Prewitt, Lara Counts, Douglas A Luke, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-quality clinical care requires excellent interdisciplinary communication, especially during emergencies, and no tools exist to evaluate communication in critical care. We describe the development of a pragmatic tool focusing on interdisciplinary communication during patient deterioration (CritCom).

METHODS: The preliminary CritCom tool was developed after a literature review and consultation with a multidisciplinary panel of global experts in communication, pediatric oncology, and critical care to review the domains and establish content validity iteratively. Face and linguistic validity were established through cognitive interviews, translation, and linguistic synthesis. We conducted a pilot study among an international group of clinicians to establish reliability …

What Can State Medical Boards Do To Effectively Address Serious Ethical Violations?, Tristan Mcintosh, Elizabeth Pendo, Heidi A Walsh, Kari A Baldwin, Patricia King, Emily E Anderson, Catherine V Caldicott, Jeffrey D Carter, Sandra H Johnson, Katherine Mathews, William A Norcross, Dana C Shaffer, James M Dubois

2020-Current year OA Pubs

State Medical Boards (SMBs) can take severe disciplinary actions (e.g., license revocation or suspension) against physicians who commit egregious wrongdoing in order to protect the public. However, there is noteworthy variability in the extent to which SMBs impose severe disciplinary action. In this manuscript, we present and synthesize a subset of 11 recommendations based on findings from our team's larger consensus-building project that identified a list of 56 policies and legal provisions SMBs can use to better protect patients from egregious wrongdoing by physicians.