bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene editing technology for improving life quality: A dream coming true?
Authors: Ramezankhani Roya , Minaei Neda , Haddadi Mahnaz , Torabi Shukoofeh , Hesaraki Mahdi , Mirzaei Hamed , Vosough Massoud , Verfaillie Catherine M. 
Published: June 2020

AbstractThe fact that monogenic diseases are related to mutations in one specific gene, make gene correction one of the promising strategies in the future to treat genetic diseases or alleviate their symptoms. From this perspective, and along with recent advances in technology, genome editing tools have gained momentum and developed fast. In fact, clustered regularly interspaced short palindromic repeats‐associated protein 9 (CRISPR/Cas9), transcription activator‐like effector nucleases (TALENs), and zinc‐finger nucleases (ZFNs) are regarded as novel technologies which are able to correct a number of genetic aberrations in vitro and in vivo. The number of ongoing clinical trials employing these tools has been increased showing the encouraging outcomes of these tools. However, there are still some major challenges with respect to the safety profile and directed delivery of them. In this paper, we provided updated information regarding the history, nature, methods of delivery, and application of the above‐mentioned gene editing tools along with the meganucleases (an older similar tool) based on published in vitro and in vivo studies and introduced clinical trials which employed these technologies.
Challenges and outcomes for bariatric surgery in patients with paraplegia: Case series and systematic review
Authors: Layton Georgia R. , Bhanderi Shivam , Sahloul Mohamed , Charalampakis Vasileios , Daskalakis Markos , Singhal Rishi 
Published: June 2020

SummaryIntroductionObesity contributes to a plethora of significant chronic diseases. Bariatric surgery has been demonstrated to be the most cost‐effective treatment for severe obesity and significantly reduces morbidity and mortality from metabolic syndrome.Patients with paraplegia have significantly impaired mobility and are therefore at a much higher risk of developing severe obesity and its sequelae. Bariatric surgery may bring significant improvements to mobility, morbidity and quality of life for patients with paraplegia, but evidence in the literature is poor for this group of patients.MethodsA systematic review was conducted conforming to PRISMA guidelines. The MEDLINE and Cochrane databases were searched for all articles published prior to April 2019 matching all of the keywords ‘bariatric’, ‘paraplegia’ and ‘spinal cord’. Articles were assessed for relevance and full texts reviewed.In addition, clinical records were reviewed for three patients who underwent bariatric surgery at a single UK private institution. Non‐identifiable demographic, clinical, operative and outcome data were obtained from electronic records.ResultsTwenty seven articles were retrieved from the initial database search, of which nine eligible full texts were reviewed. Eight articles were case reports or case series and the final article was a systematic review. All cases reported had positive outcomes with significant weight loss, improvement in mobility and increased quality of life. Outcomes from the three diversely aged patients in our case series were similarly positive, with no significant post‐operative complications.DiscussionPatients with obesity and paraplegia may significantly benefit from bariatric surgery. There is a need for multi‐centre cohort studies to evaluate outcomes and the choice of bariatric intervention. UK guidelines do not include criteria based on mobility or neurological deficit, resulting in a potential missed opportunity to offer a cost‐effective treatment that can significantly improve quality of life for patients with severe obesity and paraplegia.
Using knowledge mapping to rethink the gap between science and action
Authors: Vimal Ruppert , Morgans Courtney 
Published: June 2020

AbstractScholars have long stressed the need to bridge the gap between science and action and seek the most efficient use of knowledge for decision making. Many contributors have attempted to consider and understand the sociopolitical forces involved in knowledge generation and exchange. We argue, however, that a model is still needed to adequately conceptualize and frame the knowledge networks in which these processes are embedded. We devised a model for knowledge mapping as a prerequisite for knowledge management in the context of conservation. Using great ape conservation to frame our approach, we propose that knowledge mapping should be based on 2 key principles. First, each conservation network results from the conglomeration of subnetworks of expertise producing and using knowledge. Second, beyond the research‐management gradient, other dimensions, such as the scale of operation, geographic location, and organizational characteristics, must also be considered. Assessing both knowledge production and trajectory across different dimensions of the network opens new space for investigating and reducing the gap between science and action.
Incidence and treatment of positive pelvic sidewall lymph nodes in patients with rectal cancer
Authors: Jones H. G. , Radwan R. W. , Sams E. , Gibby M. , Coomer W. , Jeffries J. , Codd R. J. , Williams G. L. , Taylor G. , Horwood J. 
Published: June 2020

AbstractAimThe involvement of pelvic sidewall (PSW) lymph nodes in rectal cancer is a marker of locally advanced disease and poor prognosis. Eastern countries generally advocate lateral lymph node dissection (LLND) over the Western approach of neoadjuvant chemoradiotherapy and more limited surgery. The aim of this study was to evaluate how these advanced cancers were treated in three UK Health Boards.MethodologyThis was a retrospective review of three colorectal multidisciplinary team meetings from 2008 to 2016. All patients with rectal cancer and suspicious PSW lymph nodes on pretreatment MRI were included.ResultsThere were 153 (6.2%) patients who met the inclusion criteria from a total of 2461 diagnosed rectal cancers. There was significant variability between the three centres with surgical intervention ranging from 59.2% to 84.4%, P = 0.015. There were 81 patients who had neoadjuvant chemoradiotherapy prior to surgery; of these 67 (82.7%) still had positive PSW nodes on the restaging MRI, but only 13 (19.4%) had LLND. There was no difference in local recurrence (15.3% vs 11.8%, P = 0.66), 5‐year overall survival (69.2% vs 80.1%, P = 0.16) or 5‐year disease‐free survival (69.2% vs 79.4%, P = 0.72) between patients having LLND and those receiving standard neoadjuvant treatment followed by total mesorectal excision surgery.ConclusionsThis study has demonstrated that rectal cancer patients with PSW positive nodal disease have advanced disease, mostly of the lower rectum, and receive a highly heterogeneous spectrum of therapies, even within a relatively small geographical area. Greater accuracy in our preoperative staging is needed to select those patients who will benefit from LLND surgery.
Long‐term outcome with focus on pulmonary hypertension in Obesity Hypoventilation Syndrome
Authors: Budweiser Stephan , Tratz Florian , Gfüllner Florian , Pfeifer Michael 
Published: June 2020

AbstractIntroductionPulmonary Hypertension (PH) is a frequent comorbidity in Obesity Hypoventilation Syndrome (OHS).ObjectiveWe investigated long‐term outcome of OHS with a particular emphasis on PH.MethodsIn a prospective design, 64 patients with OHS and established noninvasive positive pressure ventilation (NPPV), were assessed by serum biomarkers, right heart catheterization, blood gases analysis, lung function, Epworth‐Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), World Health Organization‐functional class (WHO‐FC) and health‐related quality of life (HRQL) via the Severe Respiratory Insufficiency (SRI) questionnaire. After a planned follow‐up of 5 years patients were reassessed regarding vital status, WHO‐FC, ESS, SRI, PSQI, body mass index (BMI) and NPPV use. Prognostic markers were explored using univariate and multivariate Cox regression analyses.ResultsAt the 5‐year follow‐up, BMI tended to decrease (P = 0.05), while WHO‐FC, ESS and PSQI remained unchanged. HRQL deteriorated in terms of SRI summary score and most subdomains (P < .05 each). NPPV adherence still was high (89%), while daily NPPV use increased from 6.7 (5.1; 8.0) h/d to 8.2 (7.4; 9.0) h/d (P < .05). After a 5‐year follow‐up, mortality was 25.8%. In univariate regression analyses only age > 69.5 years (HR = 4.145, 95%‐CI = 1.180‐14.565, P = 0.016), NT‐proBNP > 1256 pg/mL (HR = 5.162, 95%‐CI = 1.136‐23.467, P = 0.018), diffusion capacity for carbon monoxide (DLCO, %pred) (HR = 0.341, 95%‐CI = 0.114‐1.019, P = 0.043) and higher oxygen use during daytime (HR = 5.236, 95%‐CI = 1.489‐18.406, P = 0.004) predicted mortality. No independent factor predicting mortality was detected in multivariate analysis.ConclusionDespite a high long‐term NPPV use HRQL worsened. Age, oxygen use at baseline, DLCO (%pred) and NT‐proBNP, as a surrogate parameter for PH, were related to long‐term survival.
Predicting harmful alcohol relapse after liver transplant: The HALT score
Authors: Satapathy Sanjaya K. , Thornburgh Cody , Heda Rajiv , Jiang Yu , Kedia Satish K. , Nair Satheesh P. , Eason James D. , Maluf Daniel 
Published: June 2020

AbstractBackgroundAlcohol‐associated liver disease (AALD) is a rapidly growing indication for liver transplantation (LT). We aimed to examine various clinical, demographic, and behavioral factors to predict post‐LT alcohol relapse and graft survival.MethodsRetrospective analysis was performed on 241 LT recipients with AALD as either a primary or secondary indication for LT (2006‐2015).ResultsPatients with <6 months of alcohol abstinence had significantly increased cumulative incidence for alcohol relapse compared to those with >6 months of abstinence (P = .0041, Log‐Rank). We identified four variables to predict harmful alcohol relapse post‐LT: age at LT, non‐alcohol‐related criminal history, pre‐LT abstinence period (Ref >6 months of alcohol abstinence), and drinks per day (Ref <10 drinks/day). Area under the curve (AUC) for the final model was 0.79 (95% CI: 0.68‐0.91). Our multivariable model was evaluated with internal cross‐validation; random sampling of the study subjects 100 times yielded a median C statistic of 75 (±SD 0.097) and accuracy of 91 (±SD 0.026). The four‐variable model served to form the harmful alcohol use post‐LT (HALT) score. Graft survival remained significantly lower in patients with <6 months of pre‐LT alcohol abstinence and those with blue‐collar jobs.ConclusionThe HALT score identifies LT candidates with AALD at significant risk for alcohol relapse, potentially guiding transplant centers for pre‐ and post‐LT interventions for improved patient outcomes.
Evaluation of the Effect of Maribavir on Cardiac Repolarization in Healthy Participants: Thorough QT/QTc Study
Authors: Ilic Katarina , Song Ivy , Wu Jingyang , Martin Patrick 
Published: June 2020

Maribavir is an orally bioavailable benzimidazole riboside in clinical development for treatment of cytomegalovirus infection in patients who undergo transplantation. Maribavir was evaluated in a thorough QT (TQT) study to determine any effects on cardiac repolarization. The effect of maribavir 100 and 1,200 mg oral doses on the baseline‐adjusted and placebo‐adjusted corrected QT (QTc) interval (delta delta QTc (ddQTc)) and other electrocardiogram (ECG) parameters was assessed in a randomized, phase I, placebo‐controlled, four‐period crossover study in healthy participants (men and women ages 18–50 years). Additionally, maribavir pharmacokinetics, safety, and tolerability were investigated. Moxifloxacin (400 mg) was used as a positive control to demonstrate the study’s ability to detect QT prolongation. Digital 12‐lead Holter ECG monitoring was performed over 22 hours following study drug administration. Individual, Fridericia’s, and Bazett’s QTc intervals were calculated. Of 52 randomized participants (29 ± 8.1 years old; 31 men (60%)), 50 (96%) completed the study. For both 100‐mg and 1200‐mg doses of maribavir, analysis of ddQTc demonstrated that the upper bound of the two‐sided 90% confidence interval was below the 10‐ms threshold at all time points. The concentration–effect analysis demonstrated no relationship between ddQTc and plasma concentrations of maribavir (and its metabolite). There were no clinically meaningful changes in heart rate and systolic blood pressure. The most common adverse event was dysgeusia; no serious adverse events were reported. This TQT study demonstrated that maribavir did not have impact on cardiac repolarization.
Perioperative Dexmedetomidine Improves Outcomes of Kidney Transplant
Authors: Chen Jun , Perez Richard , de Mattos Angelo Mario , Wang Cecilia , Li Zhongmin , Applegate Richard L. , Liu Hong 
Published: June 2020

Graft function is crucial for successful kidney transplantation. Many factors may affect graft function or cause delayed graft function (DGF), which decreases the prognosis for graft survival. This study was designed to evaluate whether the perioperative use of dexmedetomidine (Dex) could improve the incidence of function of graft kidney and complications after kidney transplantation. A total of 780 patients underwent kidney transplantations, 315 received intravenous Dex infusion during surgery, and 465 did not. Data were adjusted with propensity scores and multivariate logistic regression was used. The primary outcomes are major adverse complications, including DGF and acute rejection in the early post‐transplantation phase. The secondary outcomes included length of hospital stay (LOS), infection, overall complication, graft functional status, post‐transplantation serum creatinine values, and estimated glomerular filtration rate (eGFR). Dex use significantly decreased DGF (19.37% vs. 23.66%; adjusted odds ratio, 0.744; 95% confidence interval, 0.564–0.981; P = 0.036), risk of infection, risk of acute rejection in the early post‐transplantation phase, the risk of overall complications, and LOS. However, there were no statistical differences in 90‐day graft functional status or 7‐day, 30‐day, and 90‐day eGFR. Perioperative Dex use reduced incidence of DGF, risk of infection, risk of acute rejection, overall complications, and LOS in patients who underwent kidney transplantation.
CYP2C19 Allele Frequencies in Over 2.2 Million Direct‐to‐Consumer Genetics Research Participants and the Potential Implication for Prescriptions in a Large Health System
Authors: Ionova Yelena , Ashenhurst James , Zhan Jianan , Nhan Hoang , Kosinski Cindy , Tamraz Bani , Chubb Alison 
Published: June 2020

Understanding the prevalence of clinically relevant pharmacogenetic variants using large unselected populations is critical for gauging the potential clinical impact of widespread preemptive pharmacogenetic testing. To this end, we assessed the frequencies and ethnic distribution of the three most common CYP2C19 alleles (*2, *3, and *17) in 2.29 million direct‐to‐consumer genetics research participants (23andMe, Sunnyvale, CA). The overall frequencies of *2, *3, and *17 were 15.2%, 0.3%, and 20.4%, respectively, but varied by ethnicity. The most common variant diplotypes were *1/*17 at 26% and *1/*2 at 19.4%. The less common *2/*17, *17/*17, and *2/*2 genotypes occurred at 6.0%, 4.4%, and 2.5%, respectively. Overall, 58.3% of participants had at least one increased‐function or no‐function CYP2C19 allele. To better understand how this high frequency might impact a real patient population, we examined the prescription rates (Rx) of high‐pharmacogenetic‐risk medications metabolized by CYP2C19 using the University of California at San Francisco (UCSF) health system’s anonymized database of over 1.25 million patients. Between 2012 and 2019, a total of 151,068 UCSF patients (15.8%) representing 5 self‐reported ethnicities were prescribed one or more high‐pharmacogenetic‐risk CYP2C19 medications: proton pump inhibitors (145,243 Rx), three selective serotonin reuptake inhibitor antidepressants (54,463 Rx), clopidogrel (14,376 Rx), and voriconazole (2,303 Rx).
Safety, Pharmacokinetics, and Pharmacodynamics of TD‐0714, a Novel Potent Neprilysin Inhibitor in Healthy Adult and Elderly Subjects
Authors: Kanodia Jitendra , Lo Arthur , Baldwin R. Michael , Colley Ken , Zhou Kefei , Bourdet David L. 
Published: June 2020

TD‐0714 is an orally active, potent, and selective inhibitor of human neprilysin (NEP) in development for the treatment of chronic heart failure. Oral administration of TD‐0714 in rats resulted in dose‐dependent and sustained increases in plasma cyclic guanosine monophosphate (cGMP) over 24 hours consistent with NEP target engagement. Randomized, double‐blind, placebo controlled, single ascending dose (50–600 mg TD‐0714) and multiple ascending dose (10–200 mg TD‐0714 q.d. for 14 days) studies were conducted in healthy volunteers. TD‐0714 was generally well‐tolerated and no serious adverse events or clinically significant effects on vital signs or electrocardiogram parameters were observed. TD‐0714 exhibited dose‐proportional pharmacokinetics (PKs) with high oral bioavailability, minimal accumulation after once daily dosing, and negligible renal elimination. Pharmacodynamic (PD) responses were observed at all dose levels studied, as reflected by statistically significant increases in plasma cGMP concentrations. The increases in cGMP were significantly above the baseline (~ 50–100%) on day 14 for the entire 24‐hour interval indicating that sustained cGMP elevations are achieved at steady‐state. Maximal steady‐state cGMP response was observed in plasma and urine at doses ≥ 50 mg. The TD‐0714 PK‐PD relationship and safety profile were similar in elderly vs. younger adult subjects. The TD‐0714 PK and PD profiles support further clinical development of TD‐0714 and suggest the potential for once‐daily administration and predictable exposure in patients with cardiorenal diseases regardless of their renal function.
Small lymphocytic lymphoma mimicking primary cutaneous marginal zone lymphoma with colonization of germinal center follicles
Authors: LeBlanc Robert E. , Carter Joi B. , Kaur Prabhjot , Lansigan Frederick 
Published: June 2020

AbstractChronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is primarily a disease of older adults and is occasionally an incidental finding on skin biopsies accompanying epithelial neoplasms and insect bite reactions. In rare instances, however, it produces leukemic infiltrates showing clinical and histopathologic overlap with primary cutaneous B‐cell lymphomas including primary cutaneous marginal zone lymphoma (PCMZL). Even less frequently, such findings serve as the initial disease manifestation. We present an exceptional case of a 61‐year‐old man with no past medical history whose clinical and histopathologic findings raised consideration for PCMZL with abnormal B‐cells colonizing germinal center follicles; however, faint CD5 and CD23 co‐expression raised the differential diagnosis of CLL/SLL. In light of an ambiguous clinical presentation with widely distributed papules and plaques, peripheral blood flow cytometry was also performed, revealing high count of CLL‐type monoclonal B lymphocytosis. Subsequent workup revealed bone marrow involvement and mesenteric lymphadenopathy, supporting the diagnosis of SLL. Follicular colonization by SLL has not been previously reported. Our case underscores the importance of subtle immunophenotypic clues and correlations with clinical and radiologic findings in the workup of B‐cell lymphomas presenting in the skin.
Review of different platforms to perform rapid onsite evaluation via telecytology
Authors: Yao Keluo , Li Zaibo 
Published: June 2020

AbstractThere is increased utilisation of cytopathology to provide a rapid onsite evaluation (ROSE) of fine needle aspiration and touch preparations of small biopsies. A well‐executed ROSE procedure can significantly impact the diagnostic quality and appropriate specimen triage of procured biopsy materials. To accommodate the demand for ROSE, telecytology has been increasingly implemented to facilitate ROSE occurring remotely. Telecytology can be categorised based on camera systems including eyepiece system, camera port system and robotic microscope/whole slide image scanner system. Image sharing methods include static images, broadcast only live video streaming, teleconferencing and whole slide image management system. In this review, we will discuss the advantages and disadvantages of each of these systems and deployment considerations.
Bridging ears and eyes when learning spoken words: On the effects of bilingual experience at 30 months
Authors: Havy Mélanie , Zesiger Pascal E. 
Published: June 2020

AbstractFrom the very first moments of their lives, infants selectively attend to the visible orofacial movements of their social partners and apply their exquisite speech perception skills to the service of lexical learning. Here we explore how early bilingual experience modulates children's ability to use visible speech as they form new lexical representations. Using a cross‐modal word‐learning task, bilingual children aged 30 months were tested on their ability to learn new lexical mappings in either the auditory or the visual modality. Lexical recognition was assessed either in the same modality as the one used at learning (‘same modality’ condition: auditory test after auditory learning, visual test after visual learning) or in the other modality (‘cross‐modality’ condition: visual test after auditory learning, auditory test after visual learning). The results revealed that like their monolingual peers, bilingual children successfully learn new words in either the auditory or the visual modality and show cross‐modal recognition of words following auditory learning. Interestingly, as opposed to monolinguals, they also demonstrate cross‐modal recognition of words upon visual learning. Collectively, these findings indicate a bilingual edge in visual word learning, expressed in the capacity to form a recoverable cross‐modal representation of visually learned words.
Chinese Development Finance and its determinants: Does global governance matter?
Authors: Yoo Eunhye 
Published: June 2020

AbstractMotivationWhat motivates China to offer development finance in recipient countries? Research on Chinese development finance focuses on China’s political and economic interests in allocating development finance. Few studies, however, have assessed the impact of international norms and regulation—a neo‐institutional perspective—on China’s development finance.PurposeThe article tests the three sets of hypotheses on Chinese development finance, positing that countries will receive more Chinese aid if: (1) they have a UN General Assembly voting alliance with China and do not recognize Taiwan; (2) the more oil and gas reserves they have; and (3) the more memberships of intergovernmental organizations (IGOs), such as the UN agencies, and international non‐governmental organizations (INGOs), which include non‐profit organizations and charities, such as Oxfam, as well as foundations and professional associations.Approach and MethodsThis study models the amount of Chinese aid received by developing countries as a function of its integration to IGOs/INGO networks. It draws on data from AidData’s Global Chinese Official Finance Dataset, 2000–2014. The model used is ordinary least square regression using fixed effects.ConclusionsChinese aid allocation does not only reflect its political and economic interests. Taiwan recognition continues to be the dominant factor for Chinese development finance. IGO and INGO memberships of recipient countries increase the chance of receiving more Chinese development funding, especially for least developed countries.Policy ImplicationsChinese development finance provides many developmental opportunities for less developed countries. A key aspect of getting Chinese development finance has been alliance with China. Linkages to IGOs and INGOs also matter. Countries aiming to get Chinese development finance should consider increasing their memberships to transnational networks of IGOs and INGOs.