bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Casino Free Play on the Wagering Behavior of Light- and Medium-User Groups: The Importance of Winning at the Bottom of the Database
Authors: Lucas Anthony F. , Cho S. Ray , Singh A. K.
Published: October 2020

This study examined the extent to which free-play credits affected spend-per-trip levels in slots, with a focus on contributions from the loyalty program’s (LP) light- and medium-user tiers. These user groups represent the bulk of LP members, and also comprise the area of the database for which spending gains are most important and equivocal. Daily, tier-level performance data were collected from four different casinos, which were owned and operated by a common parent company. Analysis of player performance data failed to indicate group-level differences in the spend-per-trip results produced by free-play redeemers and non-redeemers, within each of two tiers. These findings were produced by both parametric and nonparametric measures. The free-play group (FP) recorded a mean daily T-win that was significantly greater than that generated by the no-free play group (NFP) on a maximum of 2 days (out of 365), across all four properties and both tiers. Given that the players in FP were staked with free credits, it would appear that these awards served as bankroll substitutes, rather than sources of incremental play. With respect to own-money wagering, the lack of significant increases in win on free-play trips may be most aligned with the prospect-theory-with-memory effect. While our work expanded the literature by examining decision-making under risk, beyond two stages, our results did not generally support the house-money effect. For management, our findings signaled the need for a program review, as these expensive annual campaigns comprised a substantial percentage of the casino marketing budget.
Preparing School and District Leaders for Success in Developing and Facilitating Integrative STEM in Higher Education
Authors: Geesa Rachel Louise , Stith Krista M. , Rose Mary A.
Published: October 2020

Higher education institutions in the United States with graduate-level educational leadership programs traditionally do not offer professional learning opportunities in integrative STEM education. The objective of this paper is to share our journey to prepare and implement a course designed for P-12 educational leaders to build knowledge and skills to lead impactful integrative STEM programming. Results of the demand survey indicated a high amount of interest in an integrative STEM education course. Findings from interviews and the modified Delphi study informed our decisions for the development, objectives, assessments, and outcomes of the course to enhance integrative STEM culture in educational settings.
Environmental enrichment alleviates the deleterious effects of stress in experimental autoimmune encephalomyelitis
Authors: Fournier Antoine Philippe , Baudron Erwan , Wagnon Isabelle , Aubert Philippe , Vivien Denis , Neunlist Michel , Bardou Isabelle , Docagne Fabian
Published: October 2020

Background

Clinical observations support the hypothesis that stressful events increase relapse occurrence in multiple sclerosis patients, while stress-reduction strategies can modulate this effect. However, a direct cause-effect relationship between stress level and relapse cannot be firmly established from these data.

Objectives

The purpose of this work was to address whether modulation of stress could interfere with symptom relapse in an animal model of multiple sclerosis with relapsing-remitting course.

Methods

Mice bred in standard or enriched environment were subjected to repeated acute stress during the remission phase of relapsing-remitting PLP-induced experimental autoimmune encephalomyelitis.

Results

We report that repeated acute stress induced a twofold increase in relapse incidence in experimental autoimmune encephalomyelitis. On the other hand, environmental enrichment reduced relapse incidence and severity, and reversed the effects of repeated acute stress.

Conclusion

These data provide the platform for further studies on the biological processes that link stress and multiple sclerosis relapses in a suitable animal model.
The Multi-Stakeholder’s Role in an Integrated Mentoring Model for SMEs in the Creative Economy Sector
Authors: Rosyadi Slamet , Kusuma Ayusia Sabhita , Fitrah Elpeni , Haryanto Agus , Adawiyah Wiwiek
Published: October 2020

This study aims to formulate an integrated mentoring model by involving multi-stakeholder collaboration for small and medium enterprises (SMEs) in the creative economy sector. More specifically, this study tries to identify the mentoring aspects required by SMEs in the creative economy sector and to formulate a mentoring strategy that fits their actual needs by involving multi-stakeholders. The background for the study is the lack of attention toward mentoring issues for SMEs in Banyumas Regency, Central Java, Indonesia. This qualitative research approach is conducted with a case study using SMEs’ creative economy in Banyumas Regency, Central Java, Indonesia. The data are collected by in-depth interviews and focused group discussions with creative economy actors. We analyze 25 informants representing three main subsectors of the creative economy, namely, culinary, fashion, and craft, creative economy activist and local government agency. A qualitative data analysis was made, and the results show that an integrated mentoring model comprises substantial aspects, namely, (a) marketing development, (b) business permit and legal business entity, (c) social media and information technology, (d) financial management and intellectual property protection, and (e) internationalization of market and entrepreneurship development. For more effective mentoring, the stakeholder’s participation is imperative. This article shows that the coordinated role and capacity of stakeholders may encourage flows of current experience, knowledge, and entrepreneurial spirit into the SMEs’ creative economy. Therefore, the findings of this study contribute to an understanding of multi-stakeholder involvement for SMEs in the creative economy sector through an integrated mentoring approach.
Students’ Reflections on an Experiential Learning Rotation With the Peer-Education About Weight Steadiness Club Program
Authors: Muzaffar Henna , Nikolaus Cassandra J. , Nickols-Richardson Sharon M.
Published: October 2020

Overview. Experiential learning has become a common pedagogical approach to provide university students an opportunity to apply classroom-acquired knowledge and skills in real-world settings. Evaluation of such experiences from a student perspective is needed to improve experiential learning opportunities offered in higher education settings. Purpose. The purpose of this qualitative study was to evaluate the experience of 13 university students who rotated with a healthy lifestyle program for middle schoolers. Method. The Peer-education About Weight Steadiness Club program was implemented by peer or adult educators, as a healthy lifestyle after-school intervention. Trainees participated in a learning rotation with the program for 16 weeks and were exposed to research coordination and implementation of the nutrition and healthy lifestyles program. After finishing their rotation, trainees completed a structured elicitation interview conducted by a faculty member and a graduate assistant. The 11-question individual elicitation interview, ranging from 16 to 40 minutes, queried trainees on elements of the learning experience. A grounded theory approach was used to guide data coding and analyses, which led to formulation of themes. Results. Forty codes were assigned to segments of the interview responses, which were then coalesced to formulate six themes and 16 subthemes. Identified themes include (1) program context, (2) roles and responsibilities of trainees, (3) professional development of trainees, (4) overall program implementation, (5) factors influencing implementation, and (6) health and behavioral outcomes. Conclusions. Student trainees gained program content knowledge, acquired skills transferable to their careers, valued this learning experience, and planned to apply lessons learned.
Conception rates after fluoroscopy-guided fallopian tubal cannulation: an alternative to in vitro fertilization for patients with tubal occlusion
Authors: Wang Jeffrey W. , Rustia Gabriella M. , Wood-Molo Mary , Tasse Jordan , Tabriz David , Turba Ulku C. , Arslan Bulent , Madassery Sreekumar
Published: October 2020

Objective:

Previous studies show good technical success rates for fallopian tube recanalization. Scarce literature exists regarding advance techniques currently used by interventional radiologists during fallopian tube recanalization procedures. This study investigates the level of intervention and tubal patency and its association with technical success and associated pregnancy outcomes.

Methods:

We retrospectively evaluated fallopian tube recanalization procedures performed at a single center in a 24-year period. A total of 160 couples undergoing a basic infertility evaluation were included. Hysterosalpingography with high pressure contrast injection followed by selective contrast, guidewire catheterization at the tubal ostium, and/or microcatheter/microwire recanalization were performed. Comparisons of the tubal fertilization rate by relevant characteristics were tested for statistical significance with t tests for continuous data or with Pearson chi-square tests for categorical data.

Results:

Technical success rate was 94% (319 of 341 tubes). High pressure contrast injection alone (184 of 341, 54%), selective catheterization (40%), and microcatheter/microwire (6%) interventions yielded technical success rates of 98%, 90%, and 73%, respectively. The overall rate of conception was 35% (17 of 48).

Conclusion:

Current techniques of fallopian tube recanalization offer a desirable and safe option with high technical success for patients seeking treatment for infertility due to proximal fallopian tube obstruction.
Membrane skeleton modulates erythroid proteome remodeling and organelle clearance
Authors: Liu Yijie , Mei Yang , Han Xu , Korobova Farida V. , Prado Miguel A. , Yang Jing , Peng Zhangli , Paulo Joao A. , Gygi Steven P. , Finley Daniel , Ji Peng
Published: October 2020

The final stages of mammalian erythropoiesis involve enucleation, membrane and proteome remodeling, and organelle clearance. Concomitantly, the erythroid membrane skeleton establishes a unique pseudohexagonal spectrin meshwork that is connected to the membrane through junctional complexes. The mechanism and signaling pathways involved in the coordination of these processes are unclear. The results of our study revealed an unexpected role of the membrane skeleton in the modulation of proteome remodeling and organelle clearance during the final stages of erythropoiesis. We found that diaphanous-related formin mDia2 is a master regulator of the integrity of the membrane skeleton through polymerization of actin protofilament in the junctional complex. The mDia2-deficient terminal erythroid cell contained a disorganized and rigid membrane skeleton that was ineffective in detaching the extruded nucleus. In addition, the disrupted skeleton failed to activate the endosomal sorting complex required for transport-III (ESCRT-III) complex, which led to a global defect in proteome remodeling, endolysosomal trafficking, and autophagic organelle clearance. Chmp5, a component of the ESCRT-III complex, is regulated by mDia2-dependent activation of the serum response factor and is essential for membrane remodeling and autophagosome-lysosome fusion. Mice with loss of Chmp5 in hematopoietic cells in vivo resembled the phenotypes in mDia2-knockout mice. Furthermore, overexpression of Chmp5 in mDia2-deficient hematopoietic stem and progenitor cells significantly restored terminal erythropoiesis in vivo. These findings reveal a formin-regulated signaling pathway that connects the membrane skeleton to proteome remodeling, enucleation, and organelle clearance during terminal erythropoiesis.
Outcomes in patients with DLBCL treated with commercial CAR T cells compared with alternate therapies
Authors: Sermer David , Batlevi Connie , Palomba M. Lia , Shah Gunjan , Lin Richard J. , Perales Miguel-Angel , Scordo Michael , Dahi Parastoo , Pennisi Martina , Afuye Aishat , Silverberg Mari Lynne , Ho Caleb , Flynn Jessica , Devlin Sean , Caron Philip , Hamilton Audrey , Hamlin Paul , Horwitz Steven , Joffe Erel , Kumar Anita , Matasar Matthew , Noy Ariela , Owens Colette , Moskowitz Alison , Straus David , von Keudell Gottfried , Rodriguez-Rivera Ildefonso , Falchi Lorenzo , Zelenetz Andrew , Yahalom Joachim , Younes Anas , Sauter Craig
Published: October 2020

The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Chimeric antigen receptor (CAR) T-cell therapy has been approved for R/R DLBCL after 2 prior lines of therapy based on data from single-arm phase 2 trials, with complete responses (CRs) in 40% to 60% of patients. However, a direct comparison with other treatments is not available and, moreover, its true efficacy in real-world patients is unknown. In this single center, retrospective, observational study of 215 patients, we compared outcomes in patients treated with CAR T-cell therapy (n = 69) with a historical population treated with alternate therapies (n = 146). Patients treated with CAR T cell vs alternate therapies demonstrated a CR rate of 52% vs 22% (P < .001), median progression-free survival (PFS) of 5.2 vs 2.3 months (P = .01), and median overall survival (OS) of 19.3 vs 6.5 months (P = .006), and this advantage appeared to persist irrespective of the number of lines of prior therapy. After adjusting for unfavorable pretreatment disease characteristics, superior overall response rate in the CAR T cohort remained significant; however, differences in PFS and OS between cohorts did not. In addition, patients who responded to alternate therapies demonstrated prolonged remissions comparable to those who responded to CAR T therapy. We contend that in select clinical scenarios alternate therapies may be as efficacious as CAR T therapy; thus, additional study is warranted, ideally with randomized prospective trials.
Continuous block at the proximal end of the adductor canal provides better analgesia compared to that at the middle of the canal after total knee arthroplasty: a randomized, double-blind, controlled trial
Authors: Fei Yuda , Cui Xulei , Chen Shaohui , Peng Huiming , Feng Bin , Qian Wenwei , Lin Jin , Weng Xisheng , Huang Yuguang
Published: October 2020

Background

The optimal position for continuous adductor canal block (ACB) for analgesia after total knee anthroplasty (TKA) remians controversial, mainly due to high variability in the localization of the the adductor canal (AC). Latest neuroanatomy studies show that the nerve to vastus medialis plays an important role in innervating the anteromedial aspect of the knee and dives outside of the exact AC at the proximal end of the AC. Therefore, we hypothesized that continuous ACB at the proximal end of the exact AC could provide a better analgesic effect after TKA compared with that at the middle of the AC (which appeared to only block the saphenous nerve).

Methods

Sixty-two adult patients who were scheduled for a unilateral TKA were randomized to receive continuous ACB at the proximal end or middle of the AC. All patients received patient-controlled intravenous analgesia with sufentanil postoperatively. The primary outcome measure was cumulative sufentanil consumption within 24 h after the surgery, which was analyzed using Mann-Whitney U tests. P-values < 0.05 (two-sided) were considered statistically significant. The secondary outcomes included postoperative sufentanil consumption at other time points, pain at rest and during passive knee flexion, quadriceps motor strength, and other recovery related paramaters.

Results

Sixty patients eventually completed the study (30/group). The 24-h sufentanil consumption was 0.22 μg/kg (interquartile range [IQR]: 0.15–0.40 μg/kg) and 0.39 μg/kg (IQR: 0.23–0.52 μg/kg) in the proximal end and middle groups (P = 0.026), respectively. There were no significant inter-group differences in sufentanil consumption at other time points, pain at rest and during passive knee flexion, quadriceps motor strength, and other recovery related paramaters.

Conclusions

Continuous ACB at the proximal end of the AC has a better opioid-sparing effect without a significant influence on quadriceps motor strength compared to that at the middle of the AC after TKA. These findings indicates that a true ACB may not produce the effective analgesia, instead, the proximal end AC might be a more suitable block to alleviate pain after TKA.

Trial registration

This study was registered at ClinicalTrials.gov (NCT03942133; registration date: May 06, 2019; enrollment date: May 11, 2019).
Ultrasonic detection of fetal persistent right umbilical vein and incidence and significance of concomitant anomalies
Authors: Li Jingyu , Yuan Qian , Ding Hao , Yang Zeyu , Wang Bing , Wang Bin
Published: October 2020

Background

Persistent right umbilical vein (PRUV) is characterized by atresia of the left umbilical vein while the right umbilical vein remains open. Given the limited sample size of most studies, the incidence of PRUV and the status of concomitant anomalies may not be fully reflected. Thus, we studied the incidence of fetal PRUV and its concomitant anomalies on a larger scale using our hospital database. This study hoped to address the following questions: Does PRUV increase the risk of fetal anomalies? If the PRUV fetus also has a single umbilical artery (SUA), does the risk of fetal anomaly increase further? What is the positive predictive value of PRUV for fetal anomalies?

Methods

This retrospective study analyzed 756 cases of fetal PRUV at our hospital from January 2007 to April 2017. Prenatal ultrasound and color Doppler images were assessed. All PRUV fetuses underwent echocardiography and detailed ultrasound examinations of other systems. Newborn status was obtained via the database or by telephone follow-up.

Results

A total of 435,428 pregnant women underwent prenatal ultrasonography at 16–40 weeks, the incidence of fetal PRUV was 0.17%, and 102 fetuses (13.5%) developed other anomalies. Two complicated cases had trisomy 18. PRUV was associated with a higher incidence of fetal anomalies. When fetal anomalies were classified by body systems, PRUV was associated with a higher incidence of cardiovascular, nervous, urinary, skeletal, digestive, and respiratory system anomalies. The positive predictive values of a PRUV for any fetal anomalies and cardiovascular anomalies were 13.5% (95%CI, 11.2–16.2%) and 5.4% (95%CI, 4.0–7.3%), respectively. SUA further increases the risk of PRUV fetuses with other anomalies and cardiovascular anomalies.

Conclusions

Detailed prenatal ultrasonography and echocardiography should be performed in fetuses with PRUV to rule out anomalies in other systems. When the PRUV is combined with SUA, echocardiography is particularly important. Fetuses with complicated PRUV should undergo chromosomal examination. Although isolated fetal PRUV prognosis is good, complicated PRUV prognosis depends on the type and severity of the concomitant anomalies.
Feasibility and efficacy of a supervised home-based physical exercise program for metastatic cancer patients receiving oral targeted therapy: study protocol for the phase II/III - UNICANCER SdS 01 QUALIOR trial
Authors: Joly Florence , Lefeuvre-Plesse Claudia , Garnier-Tixidre Claire , Helissey Carole , Menneveau Nathalie , Zannetti Alain , Salas Sebastien , Houede Nadine , Abadie-Lacourtoisie Sophie , Stefani Laetitia , Nenan Soazig , Rieger Isabelle , Durand-Zaleski Isabelle , Descotes Jean-Marc , Anota Amélie
Published: October 2020

Background

Currently, oral targeted therapies are known to be effective and are frequently used to treat metastatic cancer patients, but fatigue is a frequently reported early side effect of these treatments. This fatigue may impact the patient’s treatment adherence and result in a negative impact on quality of life. Physical exercise significantly improved the general well-being and quality of life of advanced cancer patients. However, there is no specific physical activity program adapted for patients with advanced disease.

Methods

QUALIOR is a two-part, randomized, open-label, and multicenter with two arms phase II/III trial. Patients (phase II: n = 120; phase III: n = 312) with metastatic cancer (breast cancer, kidney cancer, lung cancer, and other cancers [including but not limited to colon cancer, melanoma, sarcoma, or hepatocarcinoma]) treated with a first- or second-line oral targeted therapy without chemotherapy will be included. Patients will be randomized (2:1) to a 3-month supervised home-based standardized physical activity program or to a recommended adapted physical activity (via a booklet). The primary objective of the phase II is to evaluate the feasibility of the supervised program. The primary objective of the phase III is the evaluation of the benefit of the supervised home-based program compare to the recommended program in terms of fatigue and quality of life at 3 months. The secondary objectives aim to evaluate the impact of the supervised program on fatigue over time, pain, physical capacities, psychosocial and cognitive functions, general quality of life, frequency of dose reduction and patients’ adherence to the targeted therapy, overall survival, and progression-free survival. This study will also evaluate the medico-economic impact of supervised program compared to the recommended adapted physical activity program.

Discussion

The aim of this study is to evaluate home-based physical exercise program for metastatic cancer patients treated with oral targeted therapies to help patients to cope with fatigue and improve quality of life.

Trial registration

This trial was registered in ClinicalTrials.gov since May 2017 (NCT03169075).
Treatment outcome and long-term follow-up of central nervous system germ cell tumor using upfront chemotherapy with subsequent photon or proton radiation therapy: a single tertiary center experience of 127 patients
Authors: Hong Kyung Taek , Lee Da Hye , Kim Bo Kyung , An Hong Yul , Choi Jung Yoon , Phi Ji Hoon , Cheon Jung-Eun , Kang Hyoung Jin , Kim Seung-Ki , Kim Joo-Young , Park Sung-Hye , Kim Il Han , Shin Hee Young
Published: October 2020

Background

Central nervous system germ cell tumors (CNS GCTs) are a heterogeneous group of brain tumors, which are more common in Asian countries. There have been different therapeutic strategies in treating germinoma and non-germinomatous germ cell tumors (NGGCT), depending on prognosis. Moreover, long-term follow up should be emphasized due to higher late complication rates. Here, we investigated long-term outcomes and complication profiles of 127 CNS GCT patients who received uniform upfront chemotherapy.

Methods

We retrospectively evaluated outcomes of CNS GCT patients treated in Seoul National University Children’s Hospital from August 2004 to April 2019. Patients were classified as low risk (LR) or high risk (HR) based on pathologic diagnosis and tumor markers. Most patients received upfront systemic chemotherapy with carboplatin, cyclophosphamide, etoposide, and/or bleomycin, followed by either proton or photon radiation therapy according to patients’ choice.

Results

The median age at diagnosis was 11.9 (range, 3.8–25.1) years, and 54.3% of patients were LR. Photon and proton radiation therapy were administered to 73.2 and 25.2% of patients, respectively. In both LR and HR groups, there were no significant differences in survival between photon and proton radiation therapy. The 10-year relapse incidences were 9.3 and 5.6% in the LR and HR groups, respectively. All recurrences, except one, were local relapse. Six secondary malignancies occurred; the 10-year incidences of secondary malignancy were 2.2 and 7.6% in the LR and HR groups, respectively. The 10-year overall survival rates were 98.3 ± 1.7 and 91.8 ± 3.9% in the LR and HR groups, respectively. In a subgroup analysis of HR group, pathologically diagnosed NGGCT patients (n = 20) showed worse 10-year EFS (65.9 ± 11.9%, p < 0.001) and OS (77.9 ± 9.8%, p = 0.024) rates compared to other HR patients who were not pathologically diagnosed or were confirmed as germinoma with elevated tumor markers. All mortalities were related to disease progression or secondary malignancy.

Conclusion

The strategy of treating CNS GCTs with upfront chemotherapy according to risk groups resulted in good clinical outcomes and acceptable relapse incidence. However, further modification in the definition of the HR group is needed to reduce long-term complications.
Computer-aided recognition of myopic tilted optic disc using deep learning algorithms in fundus photography
Authors: Cho Baek Hwan , Lee Da Young , Park Kyung-Ah , Oh Sei Yeul , Moon Jong Hak , Lee Ga-In , Noh Hoon , Chung Joon Kyo , Kang Min Chae , Chung Myung Jin
Published: October 2020

Background

It is necessary to consider myopic optic disc tilt as it seriously impacts normal ocular parameters. However, ophthalmologic measurements are within inter-observer variability and time-consuming to get. This study aimed to develop and evaluate deep learning models that automatically recognize a myopic tilted optic disc in fundus photography.

Methods

This study used 937 fundus photographs of patients with normal or myopic tilted disc, collected from Samsung Medical Center between April 2016 and December 2018. We developed an automated computer-aided recognition system for optic disc tilt on color fundus photographs via a deep learning algorithm. We preprocessed all images with two image resizing techniques. GoogleNet Inception-v3 architecture was implemented. The performances of the models were compared with the human examiner’s results. Activation map visualization was qualitatively analyzed using the generalized visualization technique based on gradient-weighted class activation mapping (Grad-CAM++).

Results

Nine hundred thirty-seven fundus images were collected and annotated from 509 subjects. In total, 397 images from eyes with tilted optic discs and 540 images from eyes with non-tilted optic discs were analyzed. We included both eye data of most included patients and analyzed them separately in this study. For comparison, we conducted training using two aspect ratios: the simple resized dataset and the original aspect ratio (AR) preserving dataset, and the impacts of the augmentations for both datasets were evaluated. The constructed deep learning models for myopic optic disc tilt achieved the best results when simple image-resizing and augmentation were used. The results were associated with an area under the receiver operating characteristic curve (AUC) of 0.978 ± 0.008, an accuracy of 0.960 ± 0.010, sensitivity of 0.937 ± 0.023, and specificity of 0.963 ± 0.015. The heatmaps revealed that the model could effectively identify the locations of the optic discs, the superior retinal vascular arcades, and the retinal maculae.

Conclusions

We developed an automated deep learning-based system to detect optic disc tilt. The model demonstrated excellent agreement with the previous clinical criteria, and the results are promising for developing future programs to adjust and identify the effect of optic disc tilt on ophthalmic measurements.
COVID-19 multidisciplinary high dependency unit: the Milan model
Authors: Aliberti Stefano , Amati Francesco , Pappalettera Maria , Di Pasquale Marta , D’Adda Alice , Mantero Marco , Gramegna Andrea , Simonetta Edoardo , Oneta Anna Maria , Privitera Emilia , Gori Andrea , Bozzi Giorgio , Peyvandi Flora , Minoia Francesca , Filocamo Giovanni , Abbruzzese Chiara , Vicenzi Marco , Tagliabue Paola , Alongi Salvatore , Blasi Francesco
Published: October 2020

COVID-19 is a complex and heterogeneous disease. The pathogenesis and the complications of the disease are not fully elucidated, and increasing evidence shows that SARS-CoV-2 causes a systemic inflammatory disease rather than a pulmonary disease. The management of hospitalized patients in COVID-19 dedicated units is advisable for segregation purpose as well as for infection control. In this article we present the standard operating procedures of our COVID-19 high dependency unit of the Policlinico Hospital, in Milan. Our high dependency unit is based on a multidisciplinary approach. We think that the multidisciplinary involvement of several figures can better identify treatable traits of COVID-19 disease, early identify patients who can quickly deteriorate, particularly patients with multiple comorbidities, and better manage complications related to off-label treatments. Although no generalizable to other hospitals and different healthcare settings, we think that our experience and our point of view can be helpful for countries and hospitals that are now starting to face the COVID-19 outbreak.
A four prognosis-associated lncRNAs (PALnc) based risk score system reflects immune cell infiltration and predicts patient survival in pancreatic cancer
Authors: Zhuang Hongkai , Huang Shanzhou , Zhou Zixuan , Ma Zuyi , Zhang Zedan , Zhang Chuanzhao , Hou Baohua
Published: October 2020

Background

Pancreatic cancer (PC) is one of the most common cancers and the leading cause of cancer-related death worldwide. Exploring novel predictive biomarkers for PC patients’ prognosis is in urgent need.

Methods

In the present study, we conducted Cox proportional hazards regression to identify critical prognosis-associated lncRNAs (PALncs) in TCGA PC dataset. Based on the results of multivariate analysis, a PALnc-based risk score system was established, and validated in GSE62452 dataset. The validity and reliability of the risk score system for prognosis of PC were evaluated through ROC analysis. And function enrichment analyses for the PALncs were also performed.

Result

In the multivariate analysis, four PALncs (LINC00476, C9orf163, LINC00346 and DSCR9) were screened out to develop a risk score system, which showed a high AUC at 3 and 5 years overall survival (0.785 at 3 year OS, 0.863 at 5 year OS) in TCGA datasets. And the ROC analysis of the risk score system for RFS in TCGA dataset revealed that AUC for RFS was 0.799 at 3 years and 0.909 at 5 years. Further, the AUC for OS in the validation cohort was 0.705 at 3 years and 0.959 at 5 years. Furthermore, the functional enrichment analysis revealed that these PALncs may be involved in various pathways related to cancer, including Ras family activation, autophagy in cancer, MAPK signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, etc. And correlation analysis of these tumor infiltrating immune cells and risk score system revealed that the infiltration level of B cell naïve, plasma cells, and CD8+ T cells are negatively correlated to the risk score system, while macrophages M2 positively correlated to the risk score system.

Conclusion

Our study established a four PALncs based risk score system, which reflects immune cell infiltration and predicts patient survival for PC.
Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid metabolism and immune activation
Authors: Liu Honghong , Tian Ran , Wang Hui , Feng Siqin , Li Hanyu , Xiao Ying , Luan Xiaodong , Zhang Zhiyu , Shi Na , Niu Haitao , Zhang Shuyang
Published: October 2020

Background

The gut microbiota was shown to play a crucial role in the development of vascular dysfunction, and the bacterial composition differed between healthy controls and coronary artery disease patients. The goal of this study was to investigate how the gut microbiota affects host metabolic homeostasis at the organism scale.

Methods

We colonized germ-free C57BL/6 J mice with faeces from healthy control donors (Con) and coronary artery disease (CAD) patients and fed both groups a high fat diet for 12 weeks. We monitored cholesterol and vascular function in the transplanted mice. We analysed bile acids profiles and gut microbiota composition. Transcriptome sequencing and flow cytometry were performed to evaluate inflammatory and immune response.

Results

CAD mice showed increased reactive oxygen species generation and intensive arterial stiffness. Microbiota profiles in recipient mice clustered according to the microbiota structure of the human donors. Clostridium symbiosum and Eggerthella colonization from CAD patients modulated the secondary bile acids pool, leading to an increase in lithocholic acid and keto-derivatives. Subsequently, bile acids imbalance in the CAD mice inhibited hepatic bile acids synthesis and resulted in elevated circulatory cholesterol. Moreover, the faecal microbiota from the CAD patients caused a significant induction of abnormal immune responses at both the transcriptome level and through the enhanced secretion of cytokines. In addition, microbes belonging to CAD promoted intestinal inflammation by contributing to lamina propria Th17/Treg imbalance and worsened gut barrier permeability.

Conclusions

In summary, our findings elucidated that the gut microbiota impacts cholesterol homeostasis by modulating bile acids. In addition, the CAD-associated bacterial community was shown to function as an important regulator of systemic inflammation and to influence arterial stiffness.
Norwegian reference data on the Fatigue Questionnaire and the Patient Health Questionnaire-9 and their interrelationship
Authors: Dahl Alv A. , Grotmol Kjersti Støen , Hjermstad Marianne Jensen , Kiserud Cecilie Essholt , Loge Jon Håvard
Published: October 2020

Background

Population-based reference data on frequently used questionnaires are important for comparative purposes. Due to changes in health and lifestyles, such data should be updated every other decade. The objectives of this study were to establish Norwegian population-based reference data on the Fatigue Questionnaire (FQ) and the Patient Health Questionnaire-9 (PHQ-9) on depression, to compare the FQ-scores with our previous reference data from 1996, and to explore the relationship between the scores on these two instruments.

Methods

In 2015, a representative sample of 6,012 Norwegians aged 18–80 years was mailed a questionnaire including the FQ and the PHQ-9, and 36% responded. Complete FQ-scores were delivered by 2,041 subjects, and complete PHQ-9 scores by 2,086 subjects. The scores are displayed according to sex and 10-year age groups.

Results

Few 2015 mean scores of mental, physical, and total fatigue differed significantly from those of 1996, and the same was found for the prevalence rates of chronic fatigue. The exception was a significantly lower prevalence in 2015 of mean fatigue scores and prevalence of chronic fatigue in females ≥ 60 years. The prevalence of major depressive episode (MDE) based on the PHQ-9 sum score cut-off ≥ 10 was 5.9% for males and 9.8% for females, and 2.5% and 3.8% using a DSM-based algorithm with at least five endorsed criteria including either anhedonia or depressed mood. The correlation between the FQ and the PHQ-9 was 0.59, implying 36% shared variance.

Conclusions

This study showed considerable interrelationship between the FQ and the PHQ-9 constructs. The reference data show that scores on the FQ have only improved significantly in persons aged 60 or more years between 1996 and 2015. Our prevalence findings of MDE based on the PHQ-9 are in accordance with the findings from other countries. The FQ and the PHQ-9 should be used together in epidemiological and clinical studies.
Advancing understanding and identifying strategies for sustaining evidence-based practices: a review of reviews
Authors: Birken Sarah A. , Haines Emily R. , Hwang Soohyun , Chambers David A. , Bunger Alicia C. , Nilsen Per
Published: October 2020

Background

Implementation science has focused mainly on the initial uptake and use of evidence-based practices (EBPs), with less attention to sustainment—i.e., continuous use of these practices, as intended, over time in ongoing operations, often involving adaptation to dynamic contexts. Declining EBP use following implementation is well-documented yet poorly understood. Using theories, models, and frameworks (TMFs) to conceptualize sustainment could advance understanding. We consolidated knowledge from published reviews of sustainment studies to identify TMFs with the potential to conceptualize sustainment, evaluate past uses of TMFs in sustainment studies, and assess the TMFs’ potential contribution to developing sustainment strategies.

Methods

We drew upon reviews of sustainment studies published within the past 10 years, evaluated the frequency with which included articles used a TMF for conceptualizing sustainment, and evaluated the relevance of TMFs to sustainment research using the Theory, Model, and Framework Comparison and Selection Tool (T-CaST). Specifically, we examined whether the TMFs were familiar to researchers, hypothesized relationships among constructs, provided a face-valid explanation of relationships, and included sustainment as an outcome.

Findings

Nine sustainment reviews referenced 648 studies; these studies cited 76 unique TMFs. Only 28 TMFs were used in more than one study. Of the 19 TMFs that met the criteria for T-CaST analysis, six TMFs explicitly included sustainment as the outcome of interest, 12 offered face-valid explanations of proposed conceptual relationships, and six identified mechanisms underlying relationships between included constructs and sustainment. Only 11 TMFs performed adequately with respect to all these criteria.

Conclusions

We identified 76 TMFs that have been used in sustainment studies. Of these, most were only used once, contributing to a fractured understanding of sustainment. Improved reporting and use of TMFs may improve understanding of this critical topic. Of the more consistently used TMFs, few proposed face-valid relationships between included constructs and sustainment, limiting their ability to advance our understanding and identify potential sustainment strategies. Future research is needed to explore the TMFs that we identified as potentially relevant, as well as TMFs not identified in our study that nonetheless have the potential to advance our understanding of sustainment and identification of strategies for sustaining EBP use.
The effect of musical interventions in improving short-term pain outcomes following total knee replacement: a meta-analysis and systematic review
Authors: Yu Rongguo , Zhuo Youguang , Feng Eryou , Wang Wulian , Lin Wentao , Lin Feitai , Li Zhanglai , Lin Liqiong , Xiao Lili , Wang Haiyang , Huang Yuting , Wu Chunlin , Zhang Yiyuan
Published: October 2020

Background

A growing number of patients continue to receive total knee replacement (TKR) surgery. Nevertheless, such surgeries result in moderate to severe postoperative pain and difficulty in managing it. Musical interventions are regarded as a type of multimodal analgesia, achieving beneficial results in other clinical treatments. This study aims to evaluate the effect of musical interventions in improving short-term pain outcomes following TKR in order to determine a more reasonable and standard way of delivering musical intervention.

Methods

A systematic search was conducted to identify available and relevant randomized controlled trials (RCTs) regarding musical interventions compared against non-musical interventions in patients treated with TKR in Embase, MEDLINE, Cochrane Library, Web of Science, CNKI, and Wanfang Med Online up to 8 January 2020. The authors independently assessed study eligibility and risk of bias and collected the outcomes of interest to analyze. The statistical analysis was conducted using the Review Manager (RevMan) version 5.30 software.

Results

Eight RCTs comprised of 555 patients satisfied the inclusion criteria and were enrolled in the present study. The results showed no significant difference between the music and control groups in pain of the visual analog scale (VAS), during postoperative recovery room, back to the ward after surgery; anxiety degree of VAS; heart rate; respiratory rate; oxygen saturation; blood pressure, systolic blood pressure, and diastolic blood pressure. Nevertheless, significant differences were observed between the two groups in average increase in continuous passive motion (CPM) angles and LF/HF ratio (one kind index of heart rate variability).

Conclusions

Musical interventions fail to demonstrate an obvious effect in improving short-term pain outcomes following TKR. A reasonable standardization of musical interventions, including musical type, outcome measures used, outcomes measured, duration, timing and headphones or players, may improve pain outcomes with certain advantages and should be further explored after TKR.
The effect of distal tibial tuberosity high tibial osteotomy on postoperative patellar height and patellofemoral joint degeneration
Authors: Han Changxiao , Li Xia , Tian Xiangdong , Zhao Jiping , Zhou Liqun , Tan Yetong , Ma Sheng , Hu Yuanyi , Chen Handong , Huang Ye
Published: October 2020

Background

Distal tibial tuberosity high tibial osteotomy (DTT-HTO) can prevent distalization of the tibial tuberosity and thus patellar infera. However, no studies on the clinical and radiological effects of DTT-HTO on the patellofemoral joint have been conducted. The purpose of the study was to evaluate the effect of DTT-HTO on patella height and patellofemoral joint congruity based on the severity of patellofemoral joint OA.

Methods

Twenty-nine patients (33 knees) who underwent DTT-HTO and second-look arthroscopy when implant was removed between January 2018 and May 2020 were eligible for the study. Among them, 6 were males, and 23 were females, with ages from 51 to 78 years old. The Caton-Deschamps index (CDI), congruence angle (CA), and lateral patellar tilt (LPT) were measured to evaluate the effect of surgery on patellar height and patellofemoral joint congruity. The weight-bearing line ratio (WBLR) was measured to assess lower limb alignment. The cartilage lesion in the patellofemoral joint was assessed arthroscopically during surgery and implant removal by the International Cartilage Repair Society (ICRS) grading system at 18–24 months after surgery. The Hospital for Special Surgery (HSS) scale was used to evaluate knee joint function.

Results

Twenty-nine patients were followed up for 18–28 months. The preoperative CDI, CA, and LPT changed from 0.92 ± 0.16 to 0.89 ± 0.14, from 5.52 ± 2.19 to 5.44 ± 2.27, and from 6.95 ± 2.88 to 6.54 ± 2.42, respectively, and the differences were not statistically significant (p > 0.05). The preoperative WBLR significantly increased from 16.72 ± 6.77 to 58.77 ± 7.69% (p < 0.001). The cartilage lesions in the patella and femoral trochlea did not progress significantly from the first- to the second-look arthroscopy, according to the ICRS grades (p > 0.05). The HSS score significantly improved from 50.64 ± 19.18 preoperatively to 67.33 ± 14.72, 81.63 ± 11.92, and 82.73 ± 8.05 at the 3-month, 12-month, and last follow-up after surgery (p < 0.001).

Conclusion

DTT-HTO can effectively prevent patellar infera, and its effects on postoperative patellofemoral joint congruity and patellofemoral joint OA progression are inconspicuous. It can be recommended as a treatment of varus knee combined with patellar infera or patellofemoral joint OA.
Efficacy of one-stage cartilage repair using allogeneic mesenchymal stromal cells and autologous chondron transplantation (IMPACT) compared to nonsurgical treatment for focal articular cartilage lesions of the knee: study protocol for a crossover randomized controlled trial
Authors: Korpershoek J. V. , Vonk L. A. , Kester E. C. , Creemers L. B. , de Windt T. S. , Kip M. M. A. , Saris D. B. F. , Custers R. J. H.
Published: October 2020

Background

Articular cartilage defects in the knee have poor intrinsic healing capacity and may lead to functional disability and osteoarthritis (OA). “Instant MSC Product accompanying Autologous Chondron Transplantation” (IMPACT) combines rapidly isolated recycled autologous chondrons with allogeneic MSCs in a one-stage surgery. IMPACT was successfully executed in a first-in-man investigator-driven phase I/II clinical trial in 35 patients. The purpose of this study is to compare the efficacy of IMPACT to nonsurgical treatment for the treatment of large (2–8 cm2) articular cartilage defects in the knee.

Methods

Sixty patients will be randomized to receive nonsurgical care or IMPACT. After 9 months of nonsurgical care, patients in the control group are allowed to receive IMPACT surgery. The Knee Injury and Osteoarthritis Outcome Score (KOOS), pain (numeric rating scale, NRS), and EuroQol five dimensions five levels (EQ5D-5 L) will be used to compare outcomes at baseline and 3, 6, 9, 12, and 18 months after inclusion. Cartilage formation will be assessed at baseline, and 6 and 18 months after inclusion using MRI. An independent rheumatologist will monitor the onset of a potential inflammatory response. (Severe) adverse events will be recorded. Lastly, the difference between IMPACT and nonsurgical care in terms of societal costs will be assessed by monitoring healthcare resource use and productivity losses during the study period. A health economic model will be developed to estimate the incremental cost-effectiveness ratio of IMPACT vs. nonsurgical treatment in terms of costs per quality adjusted life year over a 5-year time horizon.

Discussion

This study is designed to evaluate the efficacy of IMPACT compared to nonsurgical care. Additionally, safety of IMPACT will be assessed in 30 to 60 patients. Lastly, this study will evaluate the cost-effectiveness of IMPACT compared to nonsurgical care.

Trial registration

NL67161.000.18 [Registry ID: CCMO]

2018#003470#27 [EU-CTR; registered on 26 March 2019]

NCT04236739 [ClinicalTrials.gov] [registered after start of inclusion; 22 January 2020]
The association between dietary acid load and muscle strength among Iranian adults
Authors: Mohammadpour Saba , Djafari Farhang , Davarzani Samira , Djafarian Kurosh , Clark Cain C. T. , Shab-Bidar Sakineh
Published: October 2020

Objective

There is limited evidence regarding the association between dietary acid load and muscle strength. Thus, in this study, we investigated the association between dietary acid–base load indices and muscle strength among Iranian adults.

Results

This cross-sectional study was conducted on 270 Iranian adults, aged 18–70 year. Dietary acid load indexes, were calculated by using a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Muscle strength was measured by a digital handgrip dynamometer.

There was a significant increase in mean muscle strength of left-hand (MSL), muscle strength of right-hand (MSR) and the mean of the MSL and MSR (MMS) across tertiles of Potential Renal Acid Load (PRAL), Net Endogenous Acid Production (NEAP), and Dietary Acid Load (DAL). Significant linear relationships between PRAL and; MSL (β = 0.24, p < 0.001), MSR (β = 0.23, p < 0.001) and MMS (β = 0.24, p < 0.001), between NEAP and MSL (β = 0.21, p < 0.001), MSR (β = 0.19, p = 0.002), and MMS (β = 0.20, p = 0.001) and between DAL and MSL (β = 0.25, p < 0.001), MSR (β = 0.23, p < 0.001) and MMS (β = 0.24, p < 0.001), were attenuated after controlling for potential confounders. However, the nonlinear relationship between dietary acid load indicators and muscle strength were significant (p < 0.001 for all).