bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro characterization of human bone marrow mesenchymal stem cell-derived motor neurons induced by epigenetic modifiers
Authors: Sanooghi Davood , Vahdani Parham , Bagher Zohreh , Faghihi Faezeh , Lotfi Abolfazl 
Published: June 2021

Abstract
Background
Motor neurons (MNs) are distinct types of cells in the dorso-ventral axis of the spinal cord. These cells are developed in the presence of two main morphogens, including Sonic hedgehog (Shh) and retinoic acid (RA). On the other hand, human bone marrow mesenchymal stem cells (hBM-MSCs) are known as a multipotent type of cells with neural differentiation capacity. In this regard, the aim of this study was to quantitatively evaluate the expression of MN-related genes and the potent epigenetic regulatory genes involved in neurogenesis, including Enhancer of zeste homolog 2 (EZH-2) and P300, during hBM-MSC differentiation into MN-like cells, using RA and Shh. After isolating and inducing the cells with Shh and RA, the results were evaluated using immunocytochemistry and qRT-PCR.

Results
Our findings showed that the treated cells could express choline acetyltransferase (ChAT) and insulin gene enhancer binding protein-1 (Islet-1) antigens at the protein level, 2 weeks after induction. Moreover, at the second week after induction, the induced cells expressed MN-related genes (ChAT and ISLET-1) and epigenetic regulatory genes (EZH-2 and P300) at significant levels compared to the control (non-treated BM-MSCs) and to the induced cells at the first week (day 7). In addition, the expression of EZH-2, as a histone-modifying gene, was also significantly upregulated at the first week compared to the control. No significant upregulation was detected in the expression of motor neuron and pancreas homeobox 1 (MNX-1) in the treated groups compared to the control group.

Conclusion
We concluded that epigenetic modifiers, P300 and EZH-2, are important mediators for regulating the process of motor neuron differentiation induced by RA and Shh.
Less is more: Postoperative pain management using restrictive opioid protocols in all surgical services in a comprehensive cancer center.
Authors: Ricciuti Jason , Gallo Steven , Argentieri Deanna , Visco Paul , Attwood Kristopher , Ji Wenyan , Fabiano Andrew J. , Hennon Mark , Kauffman Eric , Wooten Kimberly , Young Jessica S. , Nurkin Steven J. , de Leon-Casasola Oscar , Zsiros Emese 
Published: June 2021

103 Background: Opioids are routinely given for postoperative pain management with limited evidence on the amount needed to be dispensed. Prescribed opioids increase the risk of chronic use, abuse, and diversion, which contribute to the opioid epidemic. We sought to demonstrate that postsurgical acute pain can be effectively managed across different surgical specialties with a markedly reduced number of opioids. Methods: A prospective case-control study of restrictive opioid prescription protocol (ROPP) was implemented in all surgical services from February 2019 through July 2019 at a tertiary comprehensive cancer center for all patients undergoing a surgery for which opioids would be routinely prescribed at discharge (n = 2,015). Data from surgeries performed by the same services from August 2018 through January 2019 were used for comparison (n = 2,051). At discharge, patients did not routinely receive opioids unless they had a maximally invasive procedure or if they required multiple doses of opioids during hospitalization (maximum 3-day supply). Compliance with the protocol was tracked by pharmacists daily. Patient demographics and surgical details were collected. State-run opioid prescription database was used to determine the number of opioids prescribed to all surgical patients within a 120-day surgical window. Validated patient satisfaction surveys were used at postoperative visits to assess patient experience. Results: After implementation of the ROPP, 45% less opioids were prescribed after surgery for all participating patients (323,674 morphine milligram equivalents (MME) vs 179,458 MME, p < 0.001). The majority of services complied with the ROPP in more than 95% of cases. There was no difference in postsurgical pain intensity between cohorts. Patients in the ROPP cohort had less refill requests compared to the control group (20.9% vs 17.9%, p value = 0.016). Surveys were completed by 338 patients in the control group (16.5%) and 360 in the ROPP group (17.9%). There was no significant difference in patient reported satisfaction with postoperative pain control or on the impact of pain on daily activities between the cohorts. Conclusions: Implementation of a ROPP by multiple surgical services at a tertiary cancer center was feasible and resulted in substantial decrease in the number of opioids prescribed while not compromising patient experience. Patients did not require more prescription refills despite being provided no opioids or a limited supply. This study provides evidence to support reducing the number of opioids routinely prescribed after surgery.[Table: see text]
Imaging-based patient inclusion model for clinical trial performance optimization.
Authors: Tomaszewski Michal R , Fan Shuxuan , Qi Jin , Garcia Alberto , Kim Youngchul , Schabath Matthew B. , Gatenby Robert A , Tap William D. , Reinke Denise K. , Makanji Rikesh J , Reed Damon R. , Gillies Robert J 
Published: June 2021

105 Background: In the era of precision medicine, development of new cancer therapies relies strongly on effective selection of target patient population. We hypothesize that computational analysis of imaging data can be used for development of a quantitative population enrichment strategy in clinical trials and thus we aim to establish an appropriate framework for this analysis. Methods: This hypothesis was tested among soft-tissue sarcoma (STS) patients accrued into a randomized Phase III clinical trial (SARC021) that evaluated the efficacy of evofosfamide (Evo), a hypoxia activated prodrug, in combination with doxorubicin (Dox). Notably, SARC021 failed to meet its survival objective (PMC7771354). We tested whether an inclusion/exclusion model based on radiomic analysis and relevant clinical covariates could have been employed to result in a significant treatment benefit of the Evo+Dox combination compared to the standard Dox monotherapy. A total of 163 radiomics features were extracted from lung metastases of 303 patients from the SARC021 trial, divided into demographically matched training and test sets. Stability analysis identified the most reproducible features. Univariable and multivariable models were utilized to discriminate OS in the two treatment groups. Results: A bespoke enrichment framework was established for individualized patient selection, based on model-derived risk score threshold. A radiomic feature, Short Run Emphasis, was identified as the most informative. When combined with tumor histology and smoking history information, an enriched subset (42%) of patients had longer OS in Evo+Dox vs. Dox groups [p = 0.01, Hazard Ratio (HR) = 0.57 (0.36-0.90)], overperforming a clinical-only approach. Application of the same model and threshold value in an independent test set confirmed the significant survival difference (p = 0.002, HR = 0.29 (0.13-0.63), 38% patients included). The breakdown of Dox+Evo treatment benefit depending on proportion of patients included based on the model is shown in the Table. Notably, this process also identified patients most likely to benefit from doxorubicin alone. Conclusions: The study presents a first of its kind radiomic approach for patient enrichment in clinical trials based on a quantitative score. In particular, we have shown that had the novel model been used for selective patient inclusion into the SARC021 trial, it would have met its primary survival objective for patients with metastatic STS.[Table: see text]
Breast Cancer Index (BCI) and prediction of benefit from extended aromatase inhibitor (AI) therapy (tx) in HR+ breast cancer: NRG oncology/NSABP B-42.
Authors: Mamounas Eleftherios P. , Bandos Hanna , Rastogi Priya , Zhang Yi , Treuner Kai , Lucas Peter C. , Geyer Charles E. , Fehrenbacher Louis , Graham Mark , Chia Stephen K. L. , Brufsky Adam , Walshe Janice Maria , Soori Gamini S. , Dakhil Shaker R. , Paik Soonmyung , Swain Sandra M. , Sgroi Dennis , Schnabel Catherine A. , Wolmark Norman 
Published: June 2021

501 Background: The BCI HOXB13/IL17BR ratio (BCI-H/I) has been shown to predict endocrine tx (ET) and extended ET (EET) benefit. We examined the effect of BCI-H/I for EET benefit prediction in NSABP B-42, evaluating extended letrozole tx (ELT) in HR+ breast cancer patients (pts) who completed 5 yrs of ET. Methods: All pts with available primary tumor tissue were eligible. Primary endpoint was recurrence-free interval (RFI). Secondary endpoints were distant recurrence (DR), breast cancer-free interval (BCFI), and disease-free survival (DFS). Stratified Cox proportional hazards model was used. Due to a non-proportional effect of ELT on DR, time-dependent secondary analyses (≤4y, >4y) were performed. Likelihood ratio test evaluated treatment by BCI-H/I interaction. Results: In 2,179 pts analyzed (60% N0; 62% AI only; 80% HER2-), 45% were BCI-H/I-High and 55% BCI-H/I-Low. ELT showed an absolute 10y benefit of 1.6% for RFI (HR=0.77, 95% CI 0.57-1.05, p=0.10) (BCI-H/I-Low: 1.1% [HR=0.69, 0.43-1.11, p=0.13]; BCI-H/I-High: 2.4% [HR=0.83, 0.55-1.26, p=0.38]; interaction p=0.55). There was no statistically significant ELT by BCI-H/I interaction for BCFI (BCI-H/I-Low: HR=0.53, 0.36-0.78, p=0.001; BCI-H/I-High: HR=0.85, 0.60-1.21, p=0.36; interaction p=0.07) or for DFS (BCI-H/I-Low: HR=0.75, 0.58-0.95, p=0.017; BCI-H/I-High: HR=0.81, 0.64-1.04, p=0.09; interaction p=0.62). Before 4y, there was no statistically significant ELT benefit on DR in either BCI-H/I group. After 4y, BCI-H/I-High pts had statistically significant ELT benefit on DR (HR: 0.29, 0.12-0.69, p=0.003), while BCI-H/I-Low pts were less likely to benefit (HR: 0.68, 0.33-1.39, p=0.28) (interaction p=0.14). Conclusions: BCI-H/I prediction of ELT benefit on RFI was not confirmed. In time-dependent DR analyses, BCI-H/I-High pts had statistically significant benefit from ELT after 4y, while BCI-H/I-Low pts did not. Observed ELT benefit on BCFI in BCI-H/I-Low pts was primarily driven by second primary breast cancers. Additional follow-up is needed to further characterize BCI-H/I predictive ability in this study. Support: U10CA180868, -180822, U24CA196067; Novartis; Biotheranostics. Clinical trial information: NCT00382070. [Table: see text]
Translational CNS Steady-State Drug Disposition Model in Rats, Monkeys, and Humans for Quantitative Prediction of Brain-to-Plasma and Cerebrospinal Fluid-to-Plasma Unbound Concentration Ratios
Authors: Sato Sho , Matsumiya Kota , Tohyama Kimio , Kosugi Yohei 
Published: June 2021

AbstractCapturing unbound drug exposure in the brain is crucial to evaluate pharmacological effects for drugs acting on the central nervous system. However, to date, there are no reports of validated prediction models to determine the brain-to-plasma unbound concentration ratio (Kp,uu,brain) as well as the cerebrospinal fluid (CSF)-to-plasma unbound concentration ratio (Kp,uu,CSF) between humans and other species. Here, we developed a translational CNS steady-state drug disposition model to predict Kp,uu,brain and Kp,uu,CSF across rats, monkeys, and humans by estimating the relative activity factors (RAF) for MDR1 and BCRP in addition to scaling factors (γ and σ) using the molecular weight, logD, CSF bulk flow, and in vitro transport activities of these transporters. In this study, 68, 26, and 28 compounds were tested in the rat, monkey, and human models, respectively. Both the predicted Kp,uu,brain and Kp,uu,CSF values were within the 3-fold range of the observed values (71, 73, and 79%; 79, 88, and 78% of the compounds, respectively), indicating successful prediction of Kp,uu,brain and Kp,uu,CSF in the three species. The overall predictivity of the RAF approach is consistent with that of the relative expression factor (REF) approach. As the established model can predict Kp,uu,brain and Kp,uu,CSF using only in vitro and physicochemical data, this model would help avoid ethical issues related to animal use and improve CNS drug discovery workflow.
Effects of Including Sprints in LIT Sessions during a 14-d Camp on Muscle Biology and Performance Measures in Elite Cyclists
Authors: ALMQUIST NICKI WINFIELD , WILHELMSEN MALENE , ELLEFSEN STIAN , SANDBAKK ØYVIND , RØNNESTAD BENT R. 
Published: June 2021

ABSTRACT

Purpose
This study investigated the effects of including sprints within low-intensity training (LIT) sessions during a 14-d training camp focusing on LIT, followed by 10-d recovery (Rec), on performance and performance-related measures in elite cyclists.

Methods
During the camp, a sprint training group (SPR; n = 9) included 12 × 30-s maximal sprints during five LIT sessions, whereas a control group (CON; n = 9) performed distance-matched LIT only. Training load was equally increased in both groups by 48% ± 27% during the training camp and subsequently decreased by −56% ± 23% during the recovery period compared with habitual training. Performance tests were conducted before the training camp (Pre) and after Rec. Muscle biopsies, hematological measures, and stress/recovery questionnaires were collected Pre and after the camp (Post).

Results
Thirty-second sprint (SPR vs CON: 4% ± 4%, P < 0.01) and 5-min mean power (SPR vs CON: 4% ± 8%, P = 0.04) changed differently between groups. In muscle, Na+-K+ β1 protein content changed differently between groups, decreasing in CON compared with SPR (−8% ± 14%, P = 0.04), whereas other proteins showed similar changes. SPR and CON displayed similar increases in red blood cell volume (SPR: 2.6% ± 4.7%, P = 0.07; CON: 3.9% ± 4.5%, P = 0.02) and V˙O2 at 4 mmol·L−1 [BLa−] (SPR: 2.5% ± 3.3%, P = 0.03; CON: 2.2% ± 3.0%, P = 0.04). No changes were seen for V˙O2max, W
max, hematological measures, muscle enzyme activity, and stress/recovery measures.

Conclusions
Inclusion of 30-s sprints within LIT sessions during a high-volume training camp affected competition-relevant performance measures and Na+-K+ β1 protein content differently from LIT only, without affecting sport-specific stress/recovery or any other physiological measure in elite cyclists.
Association of COA1 with Patellar Tendonitis: A Genome-wide Association Analysis
Authors: KIM STUART K. , NGUYEN CONDOR , HORTON BRANDON H. , AVINS ANDREW L. , ABRAMS GEOFFREY D. 
Published: June 2021

ABSTRACT

Purpose
It is unknown why some athletes develop patellar tendinopathy and others do not, even when accounting for similar workloads between individuals. Genetic differences between these two populations may be a contributing factor. The purpose of this work was to screen the entire genome for genetic markers associated with patellar tendinopathy.

Methods
Genome-wide association (GWA) analyses were performed utilizing data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. Patellar tendinopathy cases were identified based on electronic health records from KPRB and UK Biobank. GWA analyses from both cohorts were tested for patellar tendinopathy using a logistic regression model adjusting for sex, height, weight, age, and race/ethnicity using allele counts for single nucleotide polymorphisms. The data from the two GWA studies (KPRB and UK Biobank) were combined in a meta-analysis.

Results
There were a total of 1670 cases of patellar tendinopathy and 293,866 controls within the two cohorts. Two single nucleotide polymorphisms located in the intron of the cytochrome c oxidase assembly factor 1 (COA1) gene showed a genome-wide significant association in the meta-analysis.

Conclusions
Genetic markers in COA1 seem to be associated with patellar tendinopathy and are potential risk factors for patellar tendinopathy that deserve further validation regarding molecular mechanisms.
Objectively Measured Physical Activity and Body Fatness: Associations with Total Body Fat, Visceral Fat, and Liver Fat
Authors: WINTERS-VAN EEKELEN ESTHER , VAN DER VELDE JEROEN H. P. M. , BOONE SEBASTIAAN C. , WESTGATE KATE , BRAGE SØREN , LAMB HILDO J. , ROSENDAAL FRITS R. , DE MUTSERT RENÉE 
Published: June 2021

ABSTRACT

Purpose
It remains unclear to what extent habitual physical activity and sedentary time (ST) are associated with visceral fat and liver fat. We studied the substitution of ST with time spent physically active and total body fat (TBF), visceral adipose tissue (VAT), and hepatic triglyceride content (HTGC) in middle-age men and women.

Design
In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, physical activity was assessed in 228 participants using a combined accelerometer and heart rate monitor. TBF was assessed by the Tanita bioelectrical impedance, VAT by magnetic resonance imaging, and HTGC by proton-MR spectroscopy. Behavioral intensity distribution was categorized as ST, time spent in light physical activity (LPA), and moderate to vigorous physical activity (MVPA). To estimate the effect of replacing 30 min·d−1 of ST with 30 min·d−1 LPA or MVPA, we performed isotemporal substitution analyses, adjusted for sex, age, ethnicity, education, the Dutch Healthy Diet index, and smoking.

Results
Included participants (41% men) had a mean ± SD age of 56 ± 6 yr and spent 88 ± 56 min in MVPA and 9.0 ± 2.1 h of ST. Replacing 30 min·d−1 of ST with 30 min of MVPA was associated with 1.3% less TBF (95% confidence interval = −2.0 to −0.7), 7.8 cm2 less VAT (−11.6 to −4.0), and 0.89 times HTGC (0.82–0.97). Replacement with LPA was not associated with TBF (−0.03%; −0.5 to 0.4), VAT (−1.7 cm2; −4.4 to 0.9), or HTGC (0.98 times; 0.92–1.04).

Conclusions
Reallocation of time spent sedentary with time spent in MVPA, but not LPA, was associated with less TBF, visceral fat, and liver fat. These findings contribute to the development of more specified guidelines on ST and physical activity.
Measuring the Impact of Crowdsourcing Features on Mobile App User Engagement and Retention: A Randomized Field Experiment
Authors: Gu Zhuojun , Bapna Ravi , Chan Jason , Gupta Alok 
Published: June 2021

The most commonly cited issues with mobile apps are low user engagement and retention levels. In this paper, we use a randomized control trial to test the efficacy of crowdsourcing on enhancing user engagement and retention in the context of mobile gaming apps. We examine two specific crowdsourcing features: the ability to submit content and the ability to access crowdsourced content. We find that the content submission significantly increases engagement and retention by reducing users’ hazard of ending a session by approximately 11% relative to the baseline and reducing the hazard of abandoning the game app by 14%. In contrast, giving users the ability to access crowdsourced content has no significant effect on engagement but has a positive effect on retention by reducing the hazard of abandoning the game app by 13%. Surprisingly, we find that the interaction effect of these two crowdsourced features is negative on user engagement. Individually, the submission feature manifests itself via empowering users to control their product use experience, whereas the access feature’s positive effect on retention is mediated by diversity and novelty of content. However, the two effects are not complementary. It turns out when these two features are given together, the empowerment enabled by one’s own submission is crowded out by others’ submissions, and this dominates the diversity benefit. Crowdsourcing features have heterogeneous impact on different user segments, with heavy users and users of longer tenure being more affected by the crowdsourcing features. This paper was accepted by Anandhi Bharadwaj, information systems.
Combating the COVID-19 Pandemic: The Role of the SARS Imprint
Authors: Ru Hong , Yang Endong , Zou Kunru 
Published: June 2021

We provide evidence of delayed attention and inaction in response to COVID-19 in countries that did not experience SARS in 2003. Using cross-country data, we find that individuals in countries that had SARS infections in 2003 searched more intensively for COVID-19-related information on Google in late January 2020, the time of the first known outbreak in Wuhan, China. Early attention to the novel virus, as measured by Google searches, is associated with deeper stock market drops in countries with SARS experience. In contrast, people in countries without SARS experience started to pay more attention much later, in March. Moreover, governments in these countries responded significantly more slowly in implementing social distancing policies to combat domestic COVID-19 outbreaks than governments in countries with SARS experience. Moreover, such early responses of individuals and governments in countries with SARS experience are prevalent within continent, even in non-Asian countries. Furthermore, people in countries with SARS experience are more compliant with social distancing rules. These timely attention and proactive responses of individuals and governments are more pronounced in countries that reported deaths caused by SARS, which left deeper imprints. Our findings suggest that the imprint of similar viruses’ experience is a fundamental mechanism underlying timely responses to COVID-19. This paper was accepted by Haoxiang Zhu, finance.
Optimized Layout of Tea Plantation Sensors Based on Improved Ant Colony Optimization
Authors: Manman Zhang , Wu Zhang , Benben Miao , Jinlei Feng , Yuan Rao , Xiu Jin 
Published: June 2021

HighlightsIn this article, an improved ant colony algorithm is proposed for optimizing the sensor placement path.The experimental data derived from field measurements.The method in this article reduces the number of sensors and the investment cost.The test results show that data redundancy, data transmission distance, and network energy consumption are reduced.Abstract. In the optimized layout of tea plantation sensors, the number and location of sensors, energy consumption of sensors, and data redundancy are all important factors that affect the layout. To reduce data redundancy, network energy loss, and the cost of sensors, an improved ant colony is proposed. The algorithm optimizes the sensor layout of the tea plantation. Introduce data redundancy and network energy consumption models into the heuristic function to guide the ants to choose the path with less data redundancy and less energy loss; add the path trend guide G to the probability transfer formula to guide the ants from the source node to the sink node Search the path, reduce the path length and the number of sensors. A tea plantation in the National High-tech Agricultural Park of Anhui Agricultural University was selected as the test area, and 25 sensor nodes were randomly arranged to collect soil moisture data for the experiment. The improved ant colony algorithm optimized the path data with less redundancy, less network energy consumption and short distance. Only 6 sensors are needed, reducing the sensor from the initial 25 to 6, which reduces the cost. In order to eliminate the accidental problem of the research results, the soil moisture data collected on 29 August 2019 was selected for the verification test, and the test results were good. Keywords: Data redundancy, Energy consumption, Improved ant colony algorithm, Soil moisture, Tea plantation.