bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Transcriptomics Analyses across Species, Organs, and Developmental Stages Reveal Functionally Constrained lncRNAs
Authors: Darbellay Fabrice , Necsulea Anamaria 
Published: September 2019

AbstractThe functionality of long noncoding RNAs (lncRNAs) is disputed. In general, lncRNAs are under weak selective pressures, suggesting that the majority of lncRNAs may be nonfunctional. However, although some surveys showed negligible phenotypic effects upon lncRNA perturbation, key biological roles were demonstrated for individual lncRNAs. Most lncRNAs with proven functions were implicated in gene expression regulation, in pathways related to cellular pluripotency, differentiation, and organ morphogenesis, suggesting that functional lncRNAs may be more abundant in embryonic development, rather than in adult organs. To test this hypothesis, we perform a multidimensional comparative transcriptomics analysis, across five developmental time points (two embryonic stages, newborn, adult, and aged individuals), four organs (brain, kidney, liver, and testes), and three species (mouse, rat, and chicken). We find that, overwhelmingly, lncRNAs are preferentially expressed in adult and aged testes, consistent with the presence of permissive transcription during spermatogenesis. LncRNAs are often differentially expressed among developmental stages and are less abundant in embryos and newborns compared with adult individuals, in agreement with a requirement for tighter expression control and less tolerance for noisy transcription early in development. For differentially expressed lncRNAs, we find that the patterns of expression variation among developmental stages are generally conserved between mouse and rat. Moreover, lncRNAs expressed above noise levels in somatic organs and during development show higher evolutionary conservation, in particular, at their promoter regions. Thus, we show that functionally constrained lncRNA loci are enriched in developing organs, and we suggest that many of these loci may function in an RNA-independent manner.
Deletion of cytochrome P450 oxidoreductase enhances metabolism and DNA adduct formation of benzo[a]pyrene in Hepa1c1c7 cells
Authors: Reed Lindsay , Jarvis Ian W H , Phillips David H , Arlt Volker M 
Published: September 2019

Abstract
The environmental carcinogen benzo[a]pyrene (BaP) is presumed to exert its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. However, studies using the Hepatic Reductase Null (HRN) mouse model, in which cytochrome P450 oxidoreductase (POR), the electron donor to CYP enzymes, is deleted specifically in hepatocytes, have shown that loss of hepatic POR-mediated CYP function leads to greater BaP-DNA adduct formation in livers of these mice than in wild-type (WT) mice. Here, we used CRISPR/Cas9 technology to knockout (KO) POR expression in mouse hepatoma Hepa1c1c7 cells to create an in vitro model that can mimic the HRN mouse model. Western blotting confirmed the deletion of POR in POR KO Hepa1c1c7 cells whereas expression of other components of the mixed-function oxidase system including cytochrome b5 (Cyb5) and NADH:cytochrome b5 reductase (which can also serve as electron donors to CYP enzymes), and CYP1A1 was similar in BaP-exposed WT and POR KO Hepa1c1c7 cells. BaP exposure caused cytotoxicity in WT Hepa1c1c7 cells but not in POR KO Hepa1c1c7 cells. In contrast, CYP-catalysed BaP-DNA adduct levels were ~10-fold higher in POR KO Hepa1c1c7 cells than in WT Hepa1c1c7 cells, in concordance with the presence of higher levels of BaP metabolite (e.g. BaP-7,8-dihydrodiol) in the medium of cultured BaP-exposed POR KO Hepa1c1c7 cells. As was seen in the HRN mouse model, these results suggest that Cyb5 contributes to the bioactivation of BaP in POR KO Hepa1c1c7 cells. These results indicate that CYP enzymes may play a more important role in the detoxication of BaP, as opposed to its bioactivation.
Comparing Retreatments and Expenditures in Flow Diversion Versus Coiling for Unruptured Intracranial Aneurysm Treatment: A Retrospective Cohort Study Using a Real-World National Database
Authors: Fukuda Haruhisa , Sato Daisuke , Kato Yoriko , Tsuruta Wataro , Katsumata Masahiro , Hosoo Hisayuki , Matsumaru Yuji , Yamamoto Tetsuya 
Published: September 2019

Abstract

BACKGROUND
Flow diverters (FDs) have marked the beginning of innovations in the endovascular treatment of large unruptured intracranial aneurysms, but no multi-institutional studies have been conducted on these devices from both the clinical and economic perspectives.

OBJECTIVE
To compare retreatment rates and healthcare expenditures between FDs and conventional coiling-based treatments in all eligible cases in Japan.

METHODS
We identified patients who had undergone endovascular treatments during the study period (October 2015-March 2018) from a national-level claims database. The outcome measures were retreatment rates and 1-yr total healthcare expenditures, which were compared among patients who had undergone FD, coiling, and stent-assisted coiling (SAC) treatments. The coiling and SAC groups were further categorized according to the number of coils used. Retreatment rates were analyzed using Cox proportional hazards models, and total expenditures were analyzed using multilevel mixed-effects generalized linear models.

RESULTS
The study sample comprised 512 FD patients, 1499 coiling patients, and 711 SAC patients. The coiling groups with ≥10 coils and ≥9 coils had significantly higher retreatment rates than the FD group with hazard ratios of 2.75 (1.30-5.82) and 2.52 (1.24-5.09), respectively. In addition, the coiling group with ≥10 coils and SAC group with ≥10 coils had significantly higher 1-year expenditures than the FD group with cost ratios (95% CI) of 1.30 (1.13-1.49) and 1.31 (1.15-1.50), respectively.

CONCLUSION
In this national-level study, FDs demonstrated significantly lower retreatment rates and total expenditures than conventional coiling with ≥ 9 coils.
Association Between Estimated Pharmacokinetic/Pharmacodynamic Predictions of Efficacy and Observed Clinical Outcomes in Obese and Nonobese Patients With Enterobacteriaceae Bloodstream Infections
Authors: Santibañez Melissa , Bunnell Kristen , Harrington Amanda , Bleasdale Susan , Wenzler Eric 
Published: September 2019

Abstract

Background
Evidence on pharmacokinetic/pharmacodynamic (PK/PD) alterations and clinical outcomes in obese patients with serious infections remains limited. This study aimed to evaluate predicted PK/PD indices of efficacy and observed clinical outcomes between obese and nonobese patients receiving cefepime or piperacillin-tazobactam for Enterobacteriaceae bacteremia.

Methods
This was a retrospective study of adult inpatients from 1/2012 to 9/2015 with Enterobacteriaceae bacteremia who received empiric cefepime or piperacillin-tazobactam. The primary outcome was clinical cure. First-dose free-drug exposure was estimated via predicted concentrations generated from population PK analyses and used to assess PD target attainment (&gt;50% fT &gt; minimum inhibitory concentration [MIC]) for the specific Enterobacteriaceae isolate. Multivariable logistic regression was utilized to identify independent predictors of clinical cure.

Results
One hundred forty-two patients were included, 57 obese and 85 nonobese. Clinical cure was achieved in 68.4% of obese and 62.4% of nonobese patients (P = .458). No significant difference in outcomes was observed when evaluated by World Health Organization (WHO) obesity classes. The PK/PD target was achieved in 98.2% of obese and 91.8% of nonobese patients (P = .144). Independent predictors of clinical cure were immunosuppression and a shorter duration of bacteremia. Obesity was not identified as a significant predictor of clinical outcomes.

Conclusions
Neither predicted PK/PD parameters nor clinical outcomes differed significantly between obese and nonobese patients treated with piperacillin-tazobactam or cefepime. As the majority of patients received extended-infusion piperacillin-tazobactam for bacteremia due to pathogens with low MICs, the potentially detrimental pathophysiologic derangements caused by obesity may not have been realized. Further studies are warranted to establish the optimal treatment of serious infections in obese patients.
Abnormal Space Experiences in Persons With Schizophrenia: An Empirical Qualitative Study
Authors: Stanghellini Giovanni , Fernandez Anthony Vincent , Ballerini Massimo , Blasi Stefano , Belfiore Erika , Cutting John , Mancini Milena 
Published: September 2019

Abstract
Abnormal space experience (ASE) is a common feature of schizophrenia, despite its absence from current diagnostic manuals. Phenomenological psychopathologists have investigated this experiential disturbance, but these studies were typically based on anecdotal evidence from limited clinical interactions. To better understand the nature of ASE in schizophrenia and attempt to validate previous phenomenological accounts, we conducted a qualitative study of 301 people with schizophrenia. Clinical files were analyzed by means of Consensual Qualitative Research, an inductive method for analyzing descriptions of lived experience. Our main findings can be summed up as follows: (1) ASEs are a relevant feature in schizophrenia (70.1% of patients reported at least 1 ASE). (2) ASE in schizophrenia are characterized by 5 main categories of phenomena (listed from more represented to less represented): (a) experiences of strangeness and unfamiliarity (eg “Everything appeared weird. Face distorted, world looks terrible, nasty”); (b) experiences of centrality/invasion of peripersonal space (eg “Handkerchief on scaffolding: message telling him something”); (c) alteration of the quality of things (eg “Buildings leaning down”); (d) alteration of the quality of the environment (eg “Person sitting six feet away seemed to be at an infinite distance”); and (e) itemization and perceptive salience (eg “All patients [in ward] have bright eyes”). (3) ASEs are much more frequent in acute (91.9%) than in chronic (28.15%) schizophrenia patients. Moreover, our findings further empirical support for phenomenological accounts of schizophrenia, including those developed by Jaspers, Binswanger, Minkowski, and Conrad, among others and provide the background for translational research.
The Effect of a Cardiovascular and Pulmonary Mobile Application on Student Learning of Assessment Skills: A Pilot Study
Authors: Bartlett Andrew S. , Smith Nancy 
Published: September 2019

Purpose/Hypothesis:
Advances in technology have recently resulted in the development of mobile learning applications (apps) for college students. Despite a recent influx of mobile apps, there is a lack of empirical data about the effectiveness of these apps on learning in the area of cardiovascular and pulmonary physical therapy (PT). The purpose of this study was to evaluate the effect of a researcher-generated cardiopulmonary mobile application on student skills in assessing blood pressure (BP), heart rate (HR), and pedal pulses.

Number of Subjects:
Twenty first-year PT graduate students were recruited for the study. Participants’ names were randomly chosen out of an envelope to assign them into 1 of 3 groups: demonstration (N = 7), mobile app (N = 7), or demonstration/mobile app (N = 6).

Materials/Methods:
After providing informed consent, each group participated in their randomized intervention. The demonstration group received demonstrations of each skill from a scripted therapist, followed by laboratory practice; the mobile app group received a 5-minute tutorial of how to use the app, followed by laboratory practice; the demonstration/mobile app group received both demonstration and the mobile app tutorial, followed by laboratory practice. Independent of group type, all participants were allotted 45 minutes in the laboratory to practice performing and interpreting BP, HR, and pedal pulses, after demonstration, demonstration/mobile app, or mobile app instruction. After the laboratory practice, participants were individually tested on the skills learned during the laboratory by a short competency examination administered by 3 licensed physical therapists. These physical therapists were blinded to each group's identity.

Results:
Total competency was highest among the demonstration/mobile app group as compared with the other 2 groups. The total competency examination score was statistically significant for different teaching methods with the use of demonstration and the mobile application being more effective than only using the mobile application P = .032. No significant difference was noted between the mobile app group and the group using demonstration only, P = .24. No other group differences were noted.

Conclusion:
Findings of this study suggest PT students demonstrate improved total competency examination scores (total score of BP, HR, and pedal pulses) when provided a mobile application combined with traditional demonstration.

Clinical Relevance:
There is currently a paucity of literature in PT education pertaining to mobile learning. The results of the current study support the use of a mobile app in addition to traditional learning methods. Future research should include a multisite design and validation of a clinical competency instrument.
Development of Algorithmic Dementia Ascertainment for Racial/Ethnic Disparities Research in the US Health and Retirement Study
Authors: Gianattasio Kan Z. , Ciarleglio Adam , Power Melinda C. 
Published: September 2019

Background:
Disparities research in dementia is limited by lack of large, diverse, and representative samples with systematic dementia ascertainment. Algorithmic diagnosis of dementia offers a cost-effective alternate approach. Prior work in the nationally representative Health and Retirement Study has demonstrated that existing algorithms are ill-suited for racial/ethnic disparities work given differences in sensitivity and specificity by race/ethnicity.

Methods:
We implemented traditional and machine learning methods to identify an improved algorithm that: (1) had ≤5 percentage point difference in sensitivity and specificity across racial/ethnic groups; (2) achieved ≥80% overall accuracy across racial/ethnic groups; and (3) achieved ≥75% sensitivity and ≥90% specificity overall. Final recommendations were based on robustness, accuracy of estimated race/ethnicity-specific prevalence and prevalence ratios compared to those using in-person diagnoses, and ease of use.

Results:
We identified six algorithms that met our prespecified criteria. Our three recommended algorithms achieved ≤3 percentage point difference in sensitivity and ≤5 percentage point difference in specificity across racial/ethnic groups, as well as 77%–83% sensitivity, 92%–94% specificity, and 90%–92% accuracy overall in analyses designed to emulate out-of-sample performance. Pairwise prevalence ratios between non-Hispanic whites, non-Hispanic blacks, and Hispanics estimated by application of these algorithms are within 1%–10% of prevalence ratios estimated based on in-person diagnoses.

Conclusions:
We believe these algorithms will be of immense value to dementia researchers interested in racial/ethnic disparities. Our process can be replicated to allow minimally biasing algorithmic classification of dementia for other purposes.
Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report
Authors: Rodeghiero Francesco , Pabinger Ingrid , Ragni Margaret , Abdul‐Kadir Rezan , Berntorp Erik , Blanchette Victor , Bodó Imre , Casini Alessandro , Gresele Paolo , Lassila Riitta , Leebeek Frank , Lillicrap David , Mezzano Diego , Noris Patrizia , Srivastava Alok , Tosetto Alberto , Windyga Jerzy , Zieger Barbara , Makris Mike , Key Nigel 
Published: September 2019

AbstractHealthy subjects frequently report minor bleedings that are frequently ‘background noise’ of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Understanding the underlying pathologic mechanism in patients with an excessive bleeding is essential for their counseling and treatment. Most of these patients with significant bleeding will result affected by non‐severe inherited bleeding disorders (BD), collectively denominated mild or moderate BD for their relatively benign course. Unfortunately, practical recommendations for the management of these disorders are still lacking due to the current state of fragmented knowledge of pathophysiology and lack of a systematic diagnostic approach. To address this gap, an International Working Group (IWG) was established by the European Hematology Association (EHA) to develop consensus‐based guidelines on these disorders. The IWG agreed that grouping these disorders by their clinical phenotype under the single category of mild‐to‐moderate bleeding disorders (MBD) reflects current clinical practice and will facilitate a systematic diagnostic approach. Based on standardized and harmonized definitions a conceptual unified framework is proposed to distinguish normal subjects from affected patients. The IWG proposes a provisional comprehensive patient‐centered initial diagnostic approach that will result in classification of MBD into distinct clinical‐pathological entities under the overarching principle of clinical utility for the individual patient. While we will present here a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence‐based, disease‐specific guidelines under development by the IWG.
Statin Use is Protective Against Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease
Authors: German Margarita N. , Lutz Megan K. , Pickhardt Perry J. , Bruce Richard J. , Said Adnan 
Published: September 2019

Background and Goal:The incidence of nonalcoholic fatty liver disease (NAFLD)–associated hepatocellular carcinoma (HCC) is rising. We aimed to characterize risk factors for NAFLD-HCC development.Methods:We performed a retrospective case-control study of HCC cases from a cohort of NAFLD patients who underwent at least 2 computed tomography scans. NAFLD-HCC cases confirmed on contrast imaging and/or biopsy were included. Controls were NAFLD patients without HCC matched by sex and age. Clinical variables were assessed. Visceral adipose tissue and subcutaneous adipose tissue were measured by computed tomography at 2 timepoints: before HCC diagnosis and at diagnosis.Results:We identified 102 subjects [34 HCC cases, 68 controls, 65% (n=66) males, mean age: 69 y] from 2002 to 2016. Cirrhosis was present in 91%. In multivariate analysis, statin use was protective against HCC [odds ratio (OR)=0.20, 95% confidence interval (CI): 0.07-0.60,P=0.004], while hypertension was a risk factor for HCC (OR=5.80, 95% CI: 2.01-16.75,P=0.001). In multivariate analysis, visceral adipose tissue in males was higher before HCC diagnosis and declined by HCC diagnosis in 86%, which was a significant difference compared with controls (OR=2.78, 95% CI: 1.10-7.44,P=0.04).Conclusions:In a cohort of NAFLD-HCC patients, statin use was protective against HCC, while hypertension conferred an increased risk. Visceral adiposity at baseline was not a risk factor, but was higher in male patients before HCC development, declining in the majority by HCC diagnosis.
The clinical and immune outcomes after food allergen immunotherapy emphasizing the development of tolerance
Authors: Miller Jennifer M. , Davis Carla M. , Anvari Sara 
Published: September 2019

Purpose of review
The present review serves to outline the direction of food allergy immunotherapy research with an emphasis on clinical and immunologic outcomes. It helps to delineate sustained unresponsiveness achieved from food immunotherapy as the clinical outcome most similar to immune tolerance.

Recent findings
We will discuss the difference between immune tolerance, desensitization, and sustained unresponsiveness in relation to food immunotherapy by discussing the clinical and immunologic changes which have been recently discovered.

Summary
Research has recently shown that oral immunotherapy is most efficacious clinically at achieving desensitization to a food and sustained unresponsiveness.
Successful Modified Transoral Endoscopic Parathyroidectomy Vestibular Approach For Secondary Hyperparathyroidism With Ectopic Mediastinal Glands
Authors: Wu Yi-Ju , Cheng Ben-Chung , Chiu Chien-Hua , Huang Shun-Chen , Li Lung-Chih , Chung Sheng-Ying , Den Chen Kuang , Pan Cheng-Chung , Li Jyun-Yi , Lin Hsiao-Wen , Chen Ying-Hsiu , Liang Peii-Ling , Co Jeffrey S. , Chi Shun-Yu , Chou Fong-Fu , Lin Chih-Che 
Published: September 2019

Background:
Transoral endoscopic parathyroidectomy vestibular approach for secondary hyperparathyroidism (SHPT) is controversial with regard to the time consumed, safety, and feasibility. We present our initial experience with modified transoral endoscopic parathyroidectomy vestibular approach (m-TOEPVA) procedure for SHPT using total parathyroidectomy with autotransplantation.

Materials and Methods:
We retrospectively reviewed 10 patients with SHPT who underwent the m-TOEPVA procedure from December 2017 to April 2018 at our center.

Results:
There were a total of 6 male individuals and 4 female individuals with a median age of 58.5 years. Among whom, 5 were on hemodialysis and 5 on peritoneal dialysis. The median length of hospital stay and operative time was 5 (4, 5) days, and 321.5 (302.75, 362.25) minutes, respectively. Successful removal of 4 parathyroid glands was achieved in 8 of 10 patients (80%) and, in 8 patients (8/10, 80%), the intact parathyroid hormone successfully dropped to <300 pg/mL at 3 months postoperatively. Two patients with ectopic parathyroid gland in the superior mediastinum were noted preoperatively by MIBI scan and subsequently had successful removal. Except for 1 patient with prolonged hospital stay (11 d) due to hungry bone syndrome, there were no other major complications.

Conclusion:
m-TOEPVA by total parathyroidectomy with autotransplantation for SHPT is feasible, safe, and offers optimal cosmetic results. The most valuable part is that m-TOEPVA provides direct visualization and successful removal of the ectopic parathyroid glands in the superior mediastinum.