bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of mucin cell-free DNA detection as a new marker for the study of acellular pseudomyxoma peritonei of appendicular origin by liquid biopsy
Authors: García-Olmo Damián , Olmedillas-López Susana , Cortés-Guiral Delia , Villarejo Pedro , López Rojo Irene , Guadalajara Héctor , García Gómez-Heras Soledad , García-Arranz Mariano 
Published: June 2020

Background: Acellular pseudomyxoma peritonei ( aPMP) is a rare peritoneal malignancy characterized by the accumulation of large amounts of mucin (lacking tumor cells) in the peritoneum. Many cases account for several kilograms of mucin to be screened by the pathologist. This is a comprehensive study of three patients with aPMP, whose tumors showed KRAS mutation, allowing for the tracking of this marker by liquid biopsy. Methods: Pre and post-surgery plasma, and mucin removed during cytoreductive surgery were collected from the patients. KRAS mutations were analyzed using droplet digital polymerase chain reaction (ddPCR). Mucin was injected in mice. KRAS and cytokine levels were measured in plasma of the mice using ddPCR and a magnetic bead-based assay. Mucin microbiome was analyzed by 16S rRNA sequencing. Results: KRAS mutations were detected in mucin cell-free DNA (cfDNA) from the three patients but not in the pre or post-surgery plasma. Electron microscopy detected microparticles (diameter <0.4 µm) in mucin. Mucin from one patient grew up inside the peritoneal cavity of mice and human KRAS was identified in mucin cfDNA, but not in plasma. All mucins showed the same bacterial profile. Cytokine levels were slightly altered in mice. Conclusions: The three aPMP patients included in this study shared some common aspects: the absence of tumor cells in mucin, the presence of KRAS mutated cfDNA in mucin, and the absence of this tumor-derived mutation in the bloodstream, providing additional information to the routine pathological examinations and suggesting that mucin cfDNA could potentially play a role in aPMP recurrence and prognosis.
The 100 Most-Cited Publications in Endoscopic Spine Surgery Research
Authors: Zhao Tingxiao , Shen Jianjian , Zheng Biao , Huang Yazeng , Jin Mengran , Morizane Kazuaki , Shao Haiyu , Chen Xinji , Zhang Jun 
Published: June 2020

Study Design: A bibliometric review of the literature. Objective: Our objective was to identify and analyze the 100 most-cited publications in the field of endoscopic spine surgery (ESS). Methods: In order to determine the top cited 100 articles, a 3-step approach was employed. First, the 100 most-cited ESS studies were identified using the key phrase “endoscopic spine surgery.” Then, 8 keywords were identified from the 100 studies of step 1 were used to conduct a second round searching in all databases of the Web of Science. Finally, when the results of the first and second steps were overlapped, duplicated studies were removed. The 100 top-cited articles were used for further analysis. Results: The citation number of the top 100 most-cited articles ranged from 44 to 236 with a mean value of 84.4. The most productive periods were from 2001 to 2010. The majority of publications came from Spine and Neurosurgery, where Spine holds the largest number of 35 articles, followed by Neurosurgery with 13 articles. Overall, 10 countries contributed to the 100 articles, with the most productive country being the United States, followed by Germany and Korea. Conclusion: This bibliometric study is meant to produce a list of intellectual milestones in the field of ESS. This article’s identification of the most influential articles in the field of ESS gives us a unique and comprehensive insight into the development of ESS in the past several decades.
Risk of Injuries Associated With Sport Specialization and Intense Training Patterns in Young Athletes: A Longitudinal Clinical Case-Control Study
Authors: Jayanthi Neeru , Kleithermes Stephanie , Dugas Lara , Pasulka Jacqueline , Iqbal Sara , LaBella Cynthia 
Published: June 2020

Background: There are no clinical longitudinal studies exploring the associations between sport specialization and intense training patterns and injuries in young athletes. Purpose: To prospectively determine the relationship between young athletes’ degree of sport specialization and their risk of injuries and reinjuries. Study Design: Case-control study; Level of evidence, 2. Methods: Young athletes aged between 7 and 18 years presenting for sports-related injuries or sports physical examinations were recruited from either sports medicine clinics or pediatric/family medicine offices. Each participant completed a baseline survey at enrollment and an identical follow-up survey every 6 months for 3 years. Surveys assessed training patterns and injuries. Injury type (acute, overuse, or serious overuse) and clinical diagnosis were also recorded from electronic medical records. Results: Of the 1208 participants who provided consent, 579 (48%) completed the baseline survey and first follow-up survey at 6 months (mean age, 14.1 ± 2.3 years; 53% female). Of this sample, 27% (158/579) of participants were uninjured, and 73% (421/579) were injured, with 29% (121/421) of injuries classified as reinjuries. Consistent with previous studies, over the 3-year study period, the degree of sport specialization had an effect such that more specialized athletes were significantly more likely to be injured ( P = .03) or have an overuse injury ( P = .02) compared with less specialized athletes after adjusting for potential confounders. Additionally, female athletes were more at risk for all injuries ( P = .01) and overuse injuries ( P = .02) after adjusting for covariates. Finally, young athletes who trained in weekly hours in excess of their age or who trained twice as many hours as their free play were significantly more likely to be injured on univariate analysis (both P < .001). Conclusion: Our study confirms that over time, young athletes, and in particular young female athletes, were more likely to be injured and sustain an overuse injury if they had a higher degree of sport specialization. Similarly, those athletes whose training hours exceeded thair age or whose sports hours exceeded their free play by a factor of greater than 2 were also more likely to develop injuries and overuse injuries.
Peak Performance: A Communications-Based Leadership and Teamwork Simulation for Fourth-Year Medical Students
Authors: Smithson Sarah , Beck Dallaghan Gary , Crowner Jason , Derry Laura Trollinger , Vijayakumar Akshitha (Ammu) , Storrie Mindy , Daaleman Timothy P 
Published: June 2020

Background: Medical education has traditionally been rooted in the teaching of health and disease processes, with little attention to the development of teamwork and leadership competencies. Objective: In an era of value-based health care provided by high-functioning teams, new approaches are needed to develop communication, leadership, and teamwork skills for medical students. Design: We designed and piloted a simulation-based educational activity called Peak Performance that linked a workbook, which focused on self-reflection on communication and leadership skills, with professional coaching. The simulation scenario placed students in the role of an upper-level resident on an inpatient service, followed by a small group debrief with students, a clinical faculty member, and a professional executive coach. After the debriefing session, students were invited to complete a self-reflection workbook within 1 week of the initial simulation. The final element of the curriculum was an individualized session with an executive coach. Peak Performance was offered to all fourth-year medical students enrolled in the Social and Health Systems Science required course at the University of North Carolina School of Medicine. Results: Pre-/post-self-assessments of leadership competencies were completed by students. Pre-simulation self-assessment scores ranged from 3.72 to 4.33 on a 5-point scale. The lowest scores were in “Managing Conflict” and “Managing Others.” The highest score was in “Self-Awareness.” The post-simulation scores decreased in every competency, with “Managing Others” dropping significantly from 3.72 pre-simulation to 3.36 post-simulation (0.31, P < .05). Satisfaction with the curriculum was high, as reflected by a Net Promoter Score of 91% (“excellent” > 50%). Conclusions: A novel simulation-based educational activity linked to professional coaching is a feasible and impactful strategy to develop leadership, communication, and teamwork skills in medical students. Student insight and self-awareness increased as evidenced by a decrease in competency self-assessment after guided reflection and individualized coaching.
How I treat gastrointestinal bleeding in congenital and acquired von Willebrand disease
Authors: Biguzzi Eugenia , Siboni Simona Maria , Peyvandi Flora 
Published: June 2020

Abstract
Gastrointestinal (GI) bleeding is distinctive of severe von Willebrand disease (VWD), generally arising in older patients; in most cases, blood transfusion and hospitalization are required. The presence of arteriovenous malformations is often described when endoscopic examinations are performed. Patients with congenital type 3, 2A, and 2B are those most frequently affected by this symptom, possibly due to the loss of high-molecular-weight multimers of von Willebrand factor (VWF). GI bleeding can also occur in patients affected by acquired von Willebrand syndrome. Endoscopic examination of the GI tract is necessary to exclude ulcers and polyps or cancer as possible causes of GI bleeding. In congenital VWD, prophylaxis with VWF/factor VIII concentrates is generally started after GI-bleeding events, but this therapy is not always successful. Iron supplementation must be prescribed to avoid chronic iron deficiency. Possible rescue therapies (high-dose statins, octreotide, thalidomide, lenalidomide, and tamoxifen) were described in a few case reports and series; however, surgery may be necessary in emergency situations or if medical treatment fails to stop bleeding. In this article, we present several clinical cases that highlight the clinical challenges of these patients and possible strategies for their long-term management.
How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies
Authors: Hill Joshua A. , Seo Susan K. 
Published: June 2020

Abstract
Adoptive immunotherapy using B-cell–targeted chimeric antigen receptor (CAR)-modified T cells to treat hematologic malignancies is transforming cancer care for patients with refractory or relapsed diseases. Recent and anticipated regulatory approval for products targeting acute lymphoblastic leukemia, lymphomas, and multiple myeloma have led to global implementation of these novel treatments. The rapidity of commercial utilization of CAR–T-cell therapy has created a largely unexplored gap in patient supportive-care approaches. Such approaches are critical in these complex patients given their high net state of immunosuppression prior to CAR–T-cell infusion coupled with unique acute and persistent insults to their immune function after CAR–T-cell infusion. In this “How I Treat” article, we focus on key questions that arise during 3 phases of management for patients receiving CD19-targeted CAR-T cells: pre CAR–T-cell infusion, immediate post CAR–T-cell infusion, and long-term follow-up. A longitudinal patient case is presented for each phase to highlight fundamental issues including infectious diseases screening, antimicrobial prophylaxis, immunoglobulin supplementation, risk factors for infection, and vaccination. We hope this discussion will provide a framework for institutions and health care providers to formulate their own approach to preventing infections in light of the paucity of data specific to this treatment modality.
MIF as a biomarker and therapeutic target for overcoming resistance to proteasome inhibitors in human myeloma
Authors: Wang Qiang , Zhao Dongyu , Xian Miao , Wang Zhuo , Bi Enguang , Su Pan , Qian Jianfei , Ma Xingzhe , Yang Maojie , Liu Lintao , Zu Youli , Pingali Sai Ravi , Chen Kaifu , Cai Zhen , Yi Qing 
Published: June 2020

AbstractMultiple myeloma (MM) remains largely incurable despite significant advances in biotherapy and chemotherapy. The development of drug resistance is a major problem in MM management. Macrophage migration inhibitory factor (MIF) expression was significantly higher in purified MM cells from relapsed patients than those with sustained response, and MM patients with high MIF had significantly shorter progression-free survival (PFS) and overall survival (OS). MM cell lines also express high levels of MIF, and knocking out MIF made them more sensitive to proteasome inhibitor (PI)-induced apoptosis not observed with other chemotherapy drugs. Mechanistic studies showed that MIF protects MM cells from PI-induced apoptosis by maintaining mitochondrial function via suppression of superoxide production in response to PIs. Specifically, MIF, in the form of a homotrimer, acts as a chaperone for superoxide dismutase 1 (SOD1) to suppress PI-induced SOD1 misfolding and to maintain SOD1 activity. MIF inhibitor 4-iodo-6-phenylpyrimidine and homotrimer disrupter ebselen, which do not kill MM cells, enhanced PI-induced SOD1 misfolding and loss of function, resulting in significantly more cell death in both cell lines and primary MM cells. More importantly, inhibiting MIF activity in vivo displayed synergistic antitumor activity with PIs and resensitized PI-resistant MM cells to treatment. In support of these findings, gene-profiling data showed a significantly negative correlation between MIF and SOD1 expression and response to PI treatment in patients with MM. This study shows that MIF plays a crucial role in MM sensitivity to PIs and suggests that targeting MIF may be a promising strategy to (re)sensitize MM to the treatment.
Circadian asthma airway responses are gated by REV-ERBα
Authors: Durrington Hannah J. , Krakowiak Karolina , Meijer Peter , Begley Nicola , Maidstone Robert , Goosey Laurence , Gibbs Julie E. , Blaikley John F. , Gregory Lisa G. , Lloyd Clare M. , Loudon Andrew S. I. , Ray D. W. 
Published: June 2020

BackgroundAsthma is an inflammatory disease of the airway showing a strong time of day rhythm. Airway hyperresponsiveness is a dominant feature of asthma, but it is not known if this is under clock control. The circadian clock powerfully regulates inflammation. The clock protein REV-ERBα is known to play a key role as a repressor of the inflammatory response.ObjectivesTo determine if allergy mediated airway hyperresponsiveness is gated by the clock protein, REV-ERBα.MethodsAfter exposure to the intra-nasal house dust mite allergen challenge model at either dawn or dusk, airway hyper-responsiveness to methacholine was measured invasively in mice.Main ResultsWild-type mice showed marked time-of-day differential responses of airway hyper-responsiveness (maximal at dusk, start of the active phase), both in vivo and ex vivo in precision cut lung slices. Hyper-responsive time of day effects were abolished in mice lacking the clock gene Rev-erbα, indicating that time-of-day effects on asthma responses are likely mediated via the circadian clock. We suggest that muscarinic receptors 1 and 3 (Chrm 1, 3) may play a role in this pathway.ConclusionsWe identify a novel circuit regulating a core process in asthma, potentially involving circadian control of muscarinic receptor expression, in a REV-ERBα dependent fashion.Clinical ImplicationThese insights suggest the importance of considering timing of drug administration in clinic trials, and in clinical practice; chronotherapy.
Open-loop analysis on sympathetically mediated arterial pressure and urine output responses in rats: effect of renal denervation
Authors: Kawada Toru , Hayama Yohsuke , Nishikawa Takuya , Suehara Satoru , Sawada Satoshi , Tanaka Tetsuo , Uenohara Minako , Sugimachi Masaru 
Published: June 2020

AbstractPrimary acute sympathetic activation (PASA) can increase arterial pressure (AP). Under this situation, the kidneys may receive mutually opposing influences from sympathetic activation: a direct anti-diuretic effect via the renal innervation and pressure diuresis. We examined whether PASA would reduce urine output regardless of the AP elevation. We also examined the impact of renal denervation (RDN) on urine output during PASA. The experiment was performed on rats 3 to 9 days after unilateral RDN (n = 10). Under anesthesia, systemic sympathetic nerve activity (SNA) was varied over a wide range via the carotid sinus baroreflex. The slope of urine flow versus SNA was positive (0.252 ± 0.052 μL·min−1·kg−1· %−1) on the intact side, and it was greater on the denervated side (0.331 ± 0.069 μL·min−1·kg−1· %−1, P < 0.05). In conclusion, urine output change was an effect of elevated AP during PASA. Nevertheless, RDN was able to augment pressure diuresis during PASA.
A blended intervention to promote physical activity, health and work productivity among office employees using intervention mapping: a study protocol for a cluster-randomized controlled trial
Authors: Sun Yan , Wang Aiwei , Yu Siyue , Hagger Martin S. , Chen Xiangyan , Fong Shirley Siu Ming , Zhang Chunqing , Huang Wendy Yajun , Baker Julien S. , Dutheil Frédéric , Gao Yang 
Published: June 2020

Abstract
Background
Regular participation in moderate-to-vigorous physical activity (MVPA) is related to decreased risk of morbidity and mortality. Among working populations, lack of MVPA may also be a risk factor for absenteeism and presenteeism. Both traditional workplace-based and web-based interventions have been suggested as being effective in promoting participation MVPA, health-related outcomes, and work-related productivity. However, several challenges limit their application in real world contexts. A ‘blended’ intervention approach combining the two intervention strategies is proposed to overcome these limitations. The proposed intervention aims to utilize the blended approach to increase participation in MVPA, health-related outcomes, and work productivity among inactive workers.

Methods
The study will comprise of a three-group cluster randomized controlled trial (cluster-RCT), comprising a three-month actual intervention and a nine-month behavioral follow-up period. The three groups will be: a web-based intervention group, a blended intervention group combining the web-based components with face-to-face workshops and posters, and a control group. Physically inactive office employees (N = 495) from 33 companies (i.e., clusters) will be recruited and randomly assigned to the three groups by cluster randomization. The intervention mapping (IM) framework will be used for selecting and applying effective health behavioral theories and behavioral change techniques (BCTs) to the development, implementation and assessment of the intervention, which will be personally tailored. The primary outcome variable will be objectively-measured MVPA using an accelerometer. Secondary outcomes will consist of indices of health including adiposity, blood pressure, blood sugar, blood lipids, self-reported depression, anxiety, stress, health-related quality of life and work-related variables including absenteeism and presenteeism.

Discussion
The proposed study adopts a robust blended intervention approach that is expected to overcome challenges in applying workplace-based and web-based interventions separately and yield larger effects in promoting MVPA participation, health-related outcomes and work productivity. Improvements in work productivity outcomes will be of particular interest to employers. If more effective, the new blended intervention has the potential to be implemented on a larger scale to benefit workplace populations.

Trial registration
The trial is prospectively registered at the ClinicalTrials.gov PRS (Trial ID: NCT04391270; Date of First Posted: May 18, 2020).
Treating periodontitis-a systematic review and meta-analysis comparing ultrasonic and manual subgingival scaling at different probing pocket depths
Authors: Zhang Xin , Hu Zixuan , Zhu Xuesong , Li Wenjie , Chen Jun 
Published: June 2020

AbstractBackgroundMechanical plaque removal has been commonly accepted to be the basis for periodontal treatment. This study aims to compare the effectiveness of ultrasonic and manual subgingival scaling at different initial probing pocket depths (PPD) in periodontal treatment.MethodsEnglish-language databases (PubMed, Cochrane Central Register of Controlled Trials, EMBASE, Medline, and ClinicalTrials.gov, by January, 2019) were searched. Weighted mean differences in primary outcomes, PPD and clinical attachment loss (CAL) reduction, were estimated by random effects model. Secondary outcomes, bleeding on probing (BOP), gingival recession (GR), and post-scaling residual dental calculus, were analyzed by comparing the results of each study. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. The GRADE approach was used to assess quality of evidence.ResultsTen randomized controlled trials were included out of 1434 identified. Initial PPD and follow-up periods formed subgroups. For 3-months follow-up: (1) too few shallow initial pocket studies available to draw a conclusion; (2) the heterogeneity of medium depth studies was so high that could not be merged to draw a conclusion; (3) deep pocket studies showed no statistical differences in PPD and CAL reduction between ultrasonic and manual groups. For 6-months follow-up: (1) too few shallow initial PPD studies to draw a conclusion; (2) at medium pocket depth, PPD reduction showed manual subgingival scaling better than ultrasound. No statistical differences were observed in CAL reduction between the two approaches; (3) for deep initial PPD studies, both PPD and CAL reduction showed manual subgingival scaling better. GR results indicated no statistical differences at medium and deep initial pocket studies between the two methods. BOP results showed more reduction at deep pocket depths with manual subgingival scaling. No conclusion could be drawn about residual dental calculus.ConclusionWhen initial PPD was 4-6 mm, PPD reduction proved manual subgingival scaling was superior, but CAL results showed no statistical differences between the two means. When initial PPD was ≥6 mm, PPD and CAL reductions suggested that manual subgingival scaling was superior.