bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Affinity GD2-Specific CAR T Cells Induce Fatal Encephalitis in a Preclinical Neuroblastoma Model
Authors: Richman Sarah A. , Nunez-Cruz Selene , Moghimi Babak , Li Lucy Z. , Gershenson Zachary T. , Mourelatos Zissimos , Barrett David M. , Grupp Stephan A. , Milone Michael C. 
Published: November 2017

Abstract
The GD2 ganglioside, which is abundant on the surface of neuroblastoma cells, is targeted by an FDA-approved therapeutic monoclonal antibody and is an attractive tumor-associated antigen for cellular immunotherapy. Chimeric antigen receptor (CAR)–modified T cells can have potent antitumor activity in B-cell malignancies, and trials to harness this cytolytic activity toward GD2 in neuroblastoma are under way. In an effort to enhance the antitumor activity of CAR T cells that target GD2, we generated variant CAR constructs predicted to improve the stability and the affinity of the GD2-binding, 14G2a-based, single-chain variable fragment (scFv) of the CAR and compared their properties in vivo. We included the E101K mutation of GD2 scFv (GD2-E101K) that has enhanced antitumor activity against a GD2+ human neuroblastoma xenograft in vivo. However, this enhanced antitumor efficacy in vivo was concomitantly associated with lethal central nervous system (CNS) toxicity comprised of extensive CAR T-cell infiltration and proliferation within the brain and neuronal destruction. The encephalitis was localized to the cerebellum and basal regions of the brain that display low amounts of GD2. Our results highlight the challenges associated with target antigens that exhibit shared expression on critical normal tissues. Despite the success of GD2-specific antibody therapies in the treatment of neuroblastoma, the fatal neurotoxicity of GD2-specific CAR T-cell therapy observed in our studies suggests that GD2 may be a difficult target antigen for CAR T-cell therapy without additional strategies that can control CAR T-cell function within the CNS. Cancer Immunol Res; 6(1); 36–46. ©2017 AACR.
Efficacy of a New Post-Mouthwash Intervention (Wiping Plus Oral Nutritional Supplements) for Preventing Aspiration Pneumonia in Elderly People: A Multicenter, Randomized, Comparative Trial
Authors: Higashiguchi Takashi , Ohara Hiroshi  , Kamakura Yayoi , Kikutani Takeshi , Kuzuya Masafumi , Enoki Hiromi , Sanada Hiromi , Matsuzaki Masami , Maruyama Michio 
Published: November 2017

<b><i>Background/Aims:</i></b> Aspiration pneumonia is a common cause of death among the elderly (≥90-year-old) in nursing homes. Studies suggest that its incidence could be reduced by oral care interventions. We aimed to evaluate the efficacy of a new oral care intervention: wiping plus oral nutritional supplements (ONS). <b><i>Methods:</i></b> This prospective observational study was conducted in 252 patients (age 88.0 ± 6.5 years) in 75 nursing homes, rehabilitation hospitals, and other care facilities. Patients were randomly divided into an intervention group (<i>n</i> = 74) and a control group (<i>n</i> = 107), whose members received conventional oral care. Body mass index, activities of daily living (Barthel index), and complete blood count and biochemistry parameters were measured at 2, 4, 6, and 8 months. <b><i>Results:</i></b> The cumulative incidence of pneumonia at 8 months tended to be lower in the intervention than in the control group (7.8 vs. 17.7%, <i>p</i> = 0.056) and was significantly lower for men in the intervention group (<i>p</i> = 0.046). <b><i>Conclusions:</i></b> Our new intervention “wiping plus providing ONS” method appears to help prevent aspiration pneumonia, thereby reducing mortality risk. In this study, we disseminate information on how this method is used in Japan.
Climatological Estimates of Hourly Tornado Probability for the United States
Authors: Krocak Makenzie J. , Brooks Harold E. 
Published: November 2017

Abstract
While there has been an abundance of research dedicated to the seasonal climatology of severe weather, very little has been done to study hazardous weather probabilities on smaller scales. To this end, local hourly climatological estimates of tornadic event probabilities were developed using storm reports from NOAA’s Storm Prediction Center. These estimates begin the process of analyzing tornado frequencies on a subdaily scale.
Characteristics of the local tornado climatology are investigated, including how the diurnal cycle varies in space and time. Hourly tornado probabilities are peaked for both the annual and diurnal cycles in the plains, whereas the southeast United States has a more variable pattern. Areas that have similar total tornado threats but differ in the distribution of that threat are highlighted. Additionally, areas that have most of the tornado threat concentrated in small time frames both annually and diurnally are compared to areas that have a low-level threat at all times. These differences create challenges related to staffing requirements and background understanding of the tornado threat unique to each region.
This work is part of a larger effort to provide background information for probabilistic forecasts of hazardous weather that are meaningful over broad time and space scales, with a focus on scales broader than the typical time and space scales of the events of interest (including current products on the “watch” scale). A large challenge remains to continue describing probabilities as the time and space scales of the forecast become comparable to the scale of the event.
Patient experience with healthcare services among older adults with serious mental illness compared to the general older population
Authors: Fortuna Karen L , Lohman Matthew C , Batsis John A , DiNapoli Elizabeth A , DiMilia Peter R , Bruce Martha L , Bartels Stephen J 
Published: November 2017

Objective To compare patient experience with healthcare services and providers among older patients (≥50 years old) with and without serious mental illness. Methods Using secondary data from the Medical Expenditures Panel Survey from 2003 through 2013, we compared adults aged 50 years and older with schizophrenia spectrum disorder ( n = 106), mood disorders (i.e., major depressive disorder and bipolar disorder) ( n = 419), and no serious mental illness ( n = 34,921). Results Older adults with schizophrenia spectrum disorder reported significantly worse provider communication than older adults without serious mental illness. Older adults with mood disorders reported the greatest barriers to shared decision-making and the greatest difficulty accessing services. Conclusions Our results highlight the need to improve the patient experience of older adults with serious mental illness. Addressing provider communication, shared decision-making, and access to care among this vulnerable group of older adults may impact clinical outcomes and costs. Future research examining the extent to which improving the patient experience may improve health outcomes and enhance treatment for this highly vulnerable older group is warranted.
Positive Margins by Oropharyngeal Subsite in Transoral Robotic Surgery for T1/T2 Squamous Cell Carcinoma
Authors: Persky Michael J. , Albergotti William G. , Rath Tanya J. , Kubik Mark W. , Abberbock Shira , Geltzeiler Mathew , Kim Seungwon , Duvvuri Umamaheswar , Ferris Robert L. 
Published: November 2017

ObjectiveTo compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins.Study DesignCase series with chart review.SettingTertiary care referral center.Subjects and MethodsWe compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results.ResultsBetween January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P =. 004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P =. 002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6‐59.6; P =. 02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status.ConclusionPositive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate.
Psychometric Assessment and Precision Remodeling of the Iowa Infant Feeding Attitude Scale to Improve Clinical Use and Efficacy Among Prenatal Women in Canada
Authors: AlKusayer Nouf M. , Midodzi William K. , Newhook Leigh Anne , Burrage Lorraine , Gill Nicole , Halfyard Beth , Twells Laurie K. 
Published: November 2017

Background: The 17-item Iowa Infant Feeding Attitude Scale (IIFAS) has been widely used to assess maternal attitudes toward infant feeding and to predict breastfeeding intention. The IIFAS has been validated among prenatal women located in Newfoundland and Labrador in Canada, although its length may prove challenging to complete in a clinical setting. Research aim: The authors aimed to reduce the number of items from the original 17-item IIFAS scale while maintaining reliability and validity. Methods: A nonexperimental cross-sectional design was used among 1,283 women in their third trimester residing in Newfoundland and Labrador. Data were collected from August 2011 to June 2016. An exploratory factor analysis using principal component analysis was performed to explore the underlying structure of the IIFAS. The internal consistency of both the 17-item and reduced version was assessed using Cronbach’s alpha and item-total correlation. The area under the curve and linear regression model were used to assess predictive validity of intention to breastfeed. Results: Our findings revealed that a 13-item IIFAS (Cronbach’s α = .870) had relatively similar internal consistency to the original IIFAS (Cronbach’s α = .868). Three themes were extracted from the factor analysis, resulting in the removal of four items. The reduced scale demonstrated an excellent ability to predict breastfeeding intention (area under the curve = 0.914). Conclusion: The reduced 13-item version of the IIFAS is a psychometrically sound instrument that maintains its accuracy and validity when measuring maternal feeding attitudes during pregnancy and can be more time efficient in clinical settings compared with the 17-item IIFAS.
Partial dopamine agonist-induced pathological gambling and impulse-control deficit on low-dose aripiprazole
Authors: Peterson Evan , Forlano Rosaria 
Published: November 2017

Objective: To describe a case of aripiprazole-induced problem gambling and impulse-control deficit in a gambling-naïve patient following commencement of low-dose aripiprazole. Method: Case report. Results: This case adds to the literature on the dopamine partial agonist aripiprazole causing or exacerbating problem gambling, and extends that literature to low-dose use of aripiprazole in the gambling naïve. Conclusions: When commencing a patient on aripiprazole the possibility of emergence of problem gambling and other impulse-control deficits should be monitored, even in those with no history of similar behaviours and even on a low dose
When and Why Do Neonatal and Pediatric Critical Care Physicians Consult Palliative Care?
Authors: Richards Claire A. , Starks Helene , O’Connor M. Rebecca , Bourget Erica , Lindhorst Taryn , Hays Ross , Doorenbos Ardith Z. 
Published: November 2017

Background: Parents of children admitted to neonatal and pediatric intensive care units (ICUs) are at increased risk of experiencing acute and post-traumatic stress disorder. The integration of palliative care may improve child and family outcomes, yet there remains a lack of information about indicators for specialty-level palliative care involvement in this setting. Objective: To describe neonatal and pediatric critical care physician perspectives on indicators for when and why to involve palliative care consultants. Methods: Semistructured interviews were conducted with 22 attending physicians from neonatal, pediatric, and cardiothoracic ICUs in a single quaternary care pediatric hospital. Transcribed interviews were analyzed using content and thematic analyses. Results: We identified 2 themes related to the indicators for involving palliative care consultants: (1) palliative care expertise including support and bridging communication and (2) organizational factors influencing communication including competing priorities and fragmentation of care. Conclusions: Palliative care was most beneficial for families at risk of experiencing communication problems that resulted from organizational factors, including those with long lengths of stay and medical complexity. The ability of palliative care consultants to bridge communication was limited by some of these same organizational factors. Physicians valued the involvement of palliative care consultants when they improved efficiency and promoted harmony. Given the increasing number of children with complex chronic conditions, it is important to support the capacity of ICU clinical teams to provide primary palliative care. We suggest comprehensive system changes and critical care physician training to include topics related to chronic illness and disability.
Increased detection of Barrett's esophagus and esophageal dysplasia with adjunctive use of wide‐area transepithelial sample with three‐dimensional computer‐assisted analysis (WATS)
Authors: Gross Seth A , Smith Michael S , Kaul Vivek ,   the US Collaborative WATS Study Group
Published: November 2017

BackgroundBarrett's esophagus (BE) and esophageal dysplasia (ED) are frequently missed during screening and surveillance esophagoscopy because of sampling error associated with four‐quadrant random forceps biopsy (FB).AimThe aim of this article is to determine if wide‐area transepithelial sampling with three‐dimensional computer‐assisted analysis (WATS) used adjunctively with FB can increase the detection of BE and ED.MethodsIn this multicenter prospective trial, patients screened for suspected BE and those with known BE undergoing surveillance were enrolled. Patients at 25 community‐based practices underwent WATS adjunctively to targeted FB and random four‐quadrant FB.ResultsOf 4203 patients, 594 were diagnosed with BE by FB alone, and 493 additional cases were detected by adding WATS, increasing the overall detection of BE by 83% (493/594, 95% CI 74%–93%). Low‐grade dysplasia (LGD) was diagnosed in 26 patients by FB alone, and 23 additional cases were detected by adding WATS, increasing the detection of LGD by 88.5% (23/26, 95% CI 48%–160%).ConclusionsAdjunctive use of WATS to FB significantly improves the detection of both BE and ED. Sampling error, an inherent limitation associated with screening and surveillance, can be improved with WATS allowing better informed decisions to be made about the management and subsequent treatment of these patients.
Putting the Brakes on Breaks: Osteoporosis Screening and Fracture Prevention
Authors: Goode Sarah C. , Beshears Jacqueline L. , Goode Russell D. , Wright Theresa F. , King Anita , Crist Brett D. 
Published: November 2017

Introduction: This prospective study sought to implement a screening tool to identify and risk stratify at-risk patients for osteoporosis and evaluate patient knowledge of osteoporosis and fragility fractures in an orthopedic trauma clinic affiliated with a level 1 trauma academic center. Methods: Of 297 eligible patients, 291 were screened and risk stratified. Patients completed an osteoporosis screening questionnaire and were risk stratified. Lifestyle advice was given to patients at low fracture risk. A dual-energy X-ray absorptiometry scan was ordered for patients at intermediate fracture risk. A referral was initiated for treatment to a bone health specialist in high fracture risk patients. Twenty patients completed a knowledge-based pretest/posttest. Results: A total of 291 patients were screened, which represented 97.7% of patients over the age of 50. Of those patients, 165 (56.7%) patients met criteria for further osteoporosis evaluation as they were considered either intermediate or high risk for future fractures. One hundred thirty-six (82.4%) patients were referred for bone mineral density evaluation. For the knowledge-based evaluation portion, patients had a 33% gain in knowledge ( P = .0004). The largest knowledge deficit identified pertained to osteoporosis risk factors and lifestyle management. Discussion: The use of an osteoporosis screening questionnaire in the orthopedic trauma clinic produced clinically significant improvement in identification of at-risk patients. A lack of knowledge regarding osteoporosis and fragility fractures was found to exist among these patients. Conclusion: The implementation of an osteoporosis screening tool to identify, risk stratify, and treat patients with osteoporosis and related fragility fractures can be successfully integrated into a busy clinical practice.
How I manage monoclonal gammopathy of undetermined significance
Authors: Go Ronald S. , Rajkumar S. Vincent 
Published: November 2017

AbstractMonoclonal gammopathy of undetermined significance (MGUS) is, in many ways, a unique hematologic entity. Unlike most hematologic conditions in which the diagnosis is intentional and credited to hematologists, the discovery of MGUS is most often incidental and made by nonhematologists. MGUS is considered an obligate precursor to several lymphoplasmacytic malignancies, including immunoglobulin light-chain amyloidosis, multiple myeloma, and Waldenström macroglobulinemia. Therefore, long-term follow-up is generally recommended. Despite its high prevalence, there is surprisingly limited evidence to inform best clinical practice both at the time of diagnosis and during follow-up. We present 7 vignettes to illustrate common clinical management questions that arise during the course of MGUS. Where evidence is present, we provide a concise summary of the literature and clear recommendations on management. Where evidence is lacking, we describe how we practice and provide a rationale for our approach. We also discuss the potential harms associated with MGUS diagnosis, a topic that is rarely, if ever, broached between patients and providers, or even considered in academic debate.
Post‐zygotic genomic changes in glutamate and dopamine pathway genes may explain discordance of monozygotic twins for schizophrenia
Authors: Castellani C. A. , Melka M. G. , Gui J. L. , Gallo A. J. , O’Reilly R. L. , Singh S. M. 
Published: November 2017

AbstractBackgroundMonozygotic twins are valuable in assessing the genetic vs environmental contribution to diseases. In the era of complete genome sequences, they allow identification of mutational mechanisms and specific genes and pathways that offer predisposition to the development of complex diseases including schizophrenia.MethodsWe sequenced the complete genomes of two pairs of monozygotic twins discordant for schizophrenia (MZD), including one representing a family tetrad. The family specific complete sequences have allowed identification of post zygotic mutations between MZD genomes. It allows identification of affected genes including relevant network and pathways that may account for the diseased state in pair specific patient.ResultsWe found multiple twin specific sequence differences between co‐twins that included small nucleotides [single nucleotide variants (SNV), small indels and block substitutions], copy number variations (CNVs) and structural variations. The genes affected by these changes belonged to a number of canonical pathways, the most prominent ones are implicated in schizophrenia and related disorders. Although these changes were found in both twins, they were more frequent in the affected twin in both pairs. Two specific pathway defects, glutamate receptor signaling and dopamine feedback in cAMP signaling pathways, were uniquely affected in the two patients representing two unrelated families.ConclusionsWe have identified genome‐wide post zygotic mutations in two MZD pairs affected with schizophrenia. It has allowed us to use the threshold model and propose the most likely cause of this disease in the two patients studied. The results support the proposition that each schizophrenia patient may be unique and heterogeneous somatic de novo events may contribute to schizophrenia threshold and discordance of the disease in monozygotic twins.
Effect of Prophylactic Human Papillomavirus (HPV) Vaccination on Oral HPV Infections Among Young Adults in the United States
Authors: Chaturvedi Anil K. , Graubard Barry I. , Broutian Tatevik , Pickard Robert K.L. , Tong Zhen-Yue , Xiao Weihong , Kahle Lisa , Gillison Maura L. 
Published: November 2017

Purpose The incidence of human papilloma virus (HPV)–positive oropharyngeal cancers has risen rapidly in recent decades among men in the United States. We investigated the US population–level effect of prophylactic HPV vaccination on the burden of oral HPV infection, the principal cause of HPV-positive oropharyngeal cancers. Methods We conducted a cross-sectional study of men and women 18 to 33 years of age (N = 2,627) within the National Health and Nutrition Examination Survey 2011 to 2014, a representative sample of the US population. Oral HPV infection with vaccine types 16, 18, 6, or 11 was compared by HPV vaccination status, as measured by self-reported receipt of at least one dose of the HPV vaccine. Analyses accounted for the complex sampling design and were adjusted for age, sex, and race. Statistical significance was assessed using a quasi-score test. Results Between 2011 and 2014, 18.3% of the US population 18 to 33 years of age reported receipt of at least one dose of the HPV vaccine before the age of 26 years (29.2% in women and 6.9% in men; P < .001). The prevalence of oral HPV16/18/6/11 infections was significantly reduced in vaccinated versus unvaccinated individuals (0.11% v 1.61%; Padj = .008), corresponding to an estimated 88.2% (95% CI, 5.7% to 98.5%) reduction in prevalence after model adjustment for age, sex, and race. Notably, the prevalence of oral HPV16/18/6/11 infections was significantly reduced in vaccinated versus unvaccinated men (0.0% v 2.13%; Padj = .007). Accounting for vaccine uptake, the population-level effect of HPV vaccination on the burden of oral HPV16/18/6/11 infections was 17.0% overall, 25.0% in women, and 6.9% in men. Conclusion HPV vaccination was associated with reduction in vaccine-type oral HPV prevalence among young US adults. However, because of low vaccine uptake, the population-level effect was modest overall and particularly low in men.