bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Long Noncoding RNANXTARin Prostate Cancer Augments Androgen Receptor Expression and Enzalutamide Resistance
Authors: Ghildiyal Ruchi , Sawant Mithila , Renganathan Arun , Mahajan Kiran , Kim Eric H. , Luo Jingqin , Dang Ha X. , Maher Christopher A. , Feng Felix Y. , Mahajan Nupam P. 
Published: November 2021

AbstractAndrogen receptor (AR) signaling continues to play a dominant role in all stages of prostate cancer, including castration-resistant prostate cancers (CRPC) that have developed resistance to second generation AR antagonists such as enzalutamide. In this study, we identified a long noncoding RNA (lncRNA), NXTAR (LOC105373241) that is located convergent with the AR gene and is repressed in human prostate tumors and cell lines. NXTAR bound upstream of the AR promoter and promoted EZH2 recruitment, causing significant loss of AR (and AR-V7) expression. Paradoxically, AR bound the NXTAR promoter, and inhibition of AR by the ACK1/TNK2 small molecule inhibitor (R)-9b excluded AR from the NXTAR promoter. The histone acetyltransferase GCN5 bound and deposited H3K14 acetylation marks, enhancing NXTAR expression. Application of an oligonucleotide derived from NXTAR exon 5 (NXTAR-N5) suppressed AR/AR-V7 expression and prostate cancer cell proliferation, indicating the translational relevance of the negative regulation of AR. In addition, pharmacologic restoration of NXTAR using (R)-9b abrogated enzalutamide-resistant prostate xenograft tumor growth. Overall, this study uncovers a positive feedback loop, wherein NXTAR acts as a novel prostate tumor-suppressing lncRNA by inhibiting AR/AR-V7 expression, which in turn upregulates NXTAR levels, compromising enzalutamide-resistant prostate cancer. The restoration of NXTAR could serve as a new therapeutic modality for patients who have acquired resistance to second generation AR antagonists.Significance:This study identifies NXTAR as a tumor suppressive lncRNA that can epigenetically downregulate AR/AR-V7 expression and provides a therapeutic strategy to reinstate NXTAR expression for treating recurrent CRPC.
Single-Cell Analysis Reveals EP4 as a Target for Restoring T-Cell Infiltration and Sensitizing Prostate Cancer to Immunotherapy
Authors: Peng Shihong , Hu Pan , Xiao Yu-Tian , Lu Weiqiang , Guo Dandan , Hu Shixiu , Xie Jiayi , Wang Minna , Yu Weiwei , Yang Junjie , Chen Huang , Zhang Xiaomin , Zhu Yasheng , Wang Ye , Yang Yue , Zhu Guanghui , Chen Sujun , Wang Jian , Zhang Bo , Chen Weidong , Wu Huangan , Sun Zhenliang , Ding Tao , Zhang Hankun , Yi Zhengfang , Liu Mingyao , Ren Shancheng 
Published: November 2021

AbstractPurpose:Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many “cold” tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy.Experimental Design:Analysis of transcriptomic profiles at single-cell resolution was performed in clinical patients' samples, along with integrated analysis of multiple RNA-sequencing datasets. The antitumor activity of YY001, a novel EP4 antagonist, combined with anti–programmed cell death protein 1 (PD-1) antibody was evaluated both in vitro and in vivo.Results:We identified EP4 (PTGER4) as expressed in epithelial cells and various immune cells and involved in modulating the prostate cancer immune microenvironment. YY001, a novel EP4 antagonist, inhibited the differentiation, maturation, and immunosuppressive function of myeloid-derived suppressor cells (MDSC) while enhancing the proliferation and anticancer functions of T cells. Furthermore, it reversed the infiltration levels of MDSCs and T cells in the tumor microenvironment by overturning the chemokine profile of tumor cells in vitro and in vivo. The combined immunotherapy demonstrated a robust antitumor immune response as indicated by the robust accumulation and activation of CD8+ cytotoxic T cells, with a significantly decreased MDSC ratio and reduced MDSC immunosuppression function.Conclusions:Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti–PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory.
Transfer Learning Based Co-Surrogate Assisted Evolutionary Bi-Objective Optimization for Objectives with Non-Uniform Evaluation Times
Authors: Wang Xilu , Jin Yaochu , Schmitt Sebastian , Olhofer Markus 
Published: November 2021

Abstract
Most existing multiobjective evolutionary algorithms (MOEAs) implicitly assume that each objective function can be evaluated within the same period of time. Typically. this is untenable in many real-world optimization scenarios where evaluation of different objectives involves different computer simulations or physical experiments with distinct time complexity. To address this issue, a transfer learning scheme based on surrogate-assisted evolutionary algorithms (SAEAs) is proposed, in which a co-surrogate is adopted to model the functional relationship between the fast and slow objective functions and a transferable instance selection method is introduced to acquire useful knowledge from the search process of the fast objective. Our experimental results on DTLZ and UF test suites demonstrate that the proposed algorithm is competitive for solving bi-objective optimization where objectives have non-uniform evaluation times.
What Helps Transformers Recognize Conversational Structure? Importance of Context, Punctuation, and Labels in Dialog Act Recognition
Authors: Żelasko Piotr , Pappagari Raghavendra , Dehak Najim 
Published: November 2021

AbstractDialog acts can be interpreted as the atomic units of a conversation, more fine-grained than utterances, characterized by a specific communicative function. The ability to structure a conversational transcript as a sequence of dialog acts—dialog act recognition, including the segmentation—is critical for understanding dialog. We apply two pre-trained transformer models, XLNet and Longformer, to this task in English and achieve strong results on Switchboard Dialog Act and Meeting Recorder Dialog Act corpora with dialog act segmentation error rates (DSER) of 8.4% and 14.2%. To understand the key factors affecting dialog act recognition, we perform a comparative analysis of models trained under different conditions. We find that the inclusion of a broader conversational context helps disambiguate many dialog act classes, especially those infrequent in the training data. The presence of punctuation in the transcripts has a massive effect on the models’ performance, and a detailed analysis reveals specific segmentation patterns observed in its absence. Finally, we find that the label set specificity does not affect dialog act segmentation performance. These findings have significant practical implications for spoken language understanding applications that depend heavily on a good-quality segmentation being available.
From Atmospheric Waves to Heatwaves: A Waveguide Perspective for Understanding and Predicting Concurrent, Persistent, and Extreme Extratropical Weather
Authors: White Rachel H. , Kornhuber Kai , Martius Olivia , Wirth Volkmar 
Published: November 2021

Abstract
A notable number of high-impact weather extremes have occurred in recent years, often associated with persistent, strongly meandering atmospheric circulation patterns known as Rossby waves. Because of the high societal and ecosystem impacts, it is of great interest to be able to accurately project how such extreme events will change with climate change, and to predict these events on seasonal-to-subseasonal (S2S) time scales. There are multiple physical links connecting upper-atmosphere circulation patterns to surface weather extremes, and it is asking a lot of our dynamical models to accurately simulate all of these. Subsequently, our confidence in future projections and S2S forecasts of extreme events connected to Rossby waves remains relatively low. We also lack full fundamental theories for the growth and propagation of Rossby waves on the spatial and temporal scales relevant to extreme events, particularly under strongly nonlinear conditions. By focusing on one of the first links in the chain from upper-atmospheric conditions to surface extremes—the Rossby waveguide—it may be possible to circumvent some model biases in later links. To further our understanding of the nature of waveguides, links to persistent surface weather events and their representation in models, we recommend exploring these links in model hierarchies of increasing complexity, developing fundamental theory, exploiting novel large ensemble datasets, harnessing deep learning, and increased community collaboration. This would help increase understanding and confidence in both S2S predictions of extremes and of projections of the impact of climate change on extreme weather events.
A Note on the Depth of Sidelobe Contamination in Acoustic Doppler Current Profiles
Authors: Lentz S. J. , Kirincich A. , Plueddemann A. J. 
Published: November 2021

Abstract
Acoustic Doppler current profilers (ADCP) do not provide reliable water velocity measurements near the sea surface or bottom because acoustic sidelobe reflections from the boundary contaminate the Doppler velocity measurements. The apparent depth of the center of the sidelobe reflection is zsl = ha[1 − cos(θ)], where ha is the distance from the ADCP acoustic head to the sea surface and θ is the ADCP beam angle. However, sidelobe contamination extends one and a half ADCP bins below zsl as the range gating of the acoustic return causes overlap between adjacent ADCP bins. Consequently, the contaminated region z < zsl + 3Δz/2 is deeper than traditionally suggested, with a dependence on bin size Δz. Direct observations confirming both the center depth of the sidelobe reflection and the depth of contamination are presented for six bottom-mounted, upward-looking ADCPs. The sidelobe reflection is isolated by considering periods of weak wind stresses when the sea surface is smooth and there is nearly perfect reflection of the main beams away from the ADCP and hence little acoustic return from the main beams to the ADCP.
Intravenous Metoprolol Versus Diltiazem for Rate Control in Atrial Fibrillation
Authors: Xiao Sheng Qi , Ibarra Francisco , Cruz Mallory 
Published: November 2021

Background Currently, it remains unclear whether β-blockers or nondihydropyridine calcium channel blockers are preferred for the acute management of atrial fibrillation (AF). Objective The objective of this study was to compare the efficacy and safety of intravenous (IV) metoprolol and diltiazem for rate control. Methods This was a single-center, retrospective cohort study of patients who presented to the emergency department between 2015 and 2019 with AF with rapid ventricular rate (RVR) and received IV metoprolol or diltiazem. The primary outcome was the percentage of patients who achieved rate control (defined as heart rate < 100 beats per minute). Secondary outcomes included time to rate control, percentage of patients requiring additional agents for rate control, and incidence of cardioversion, bradycardia, and hypotension. Results A total of 200 patients were included in this study. Rate control was achieved in 35% and 41% of the metoprolol and diltiazem groups, respectively ( P = 0.38). Mean time to rate control was not significantly different between the metoprolol and diltiazem groups (35 vs 21 minutes, P = 0.23). One patient developed hypotension, no patient developed bradycardia, and 4 patients required electric cardioversion. No adverse events were observed in patients with ejection fraction ≤40%. Conclusion and Relevance There was no difference in the achievement of rate control between IV metoprolol and diltiazem. This is the largest study to date comparing the two classes of agents for acute rate control in AF. No patient-specific factors were identified that would influence the preferential use of one medication over the other.
Evaluating the effects of duloxetine on prophylaxis of oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancer: A randomized double-blind placebo controlled clinical trial
Authors: Rokhsareh Soufi , Haghighi Shirin , Tavakoli-Ardakani Maria 
Published: November 2021

Background Oxaliplatin is a key drug in treatment of gastrointestinal (GI) cancer. Peripheral neuropathy (PN) is a troublesome and dose-dependent adverse effect of oxaliplatin. It can occur in two distinct forms: acute and chronic. Its incidence is estimated about 65-98%, of which 22% of cases need to stop chemotherapy. In some cases, PN has a long-lasting effect on patient's quality of life (QOL). Therefore, this study was done to evaluate efficacy of duloxetine on prevention of oxaliplatin- induced peripheral neuropathy (OIPN) in patients with GI cancer. Methodology In this randomized and double -blind clinical trial study conducted in a tertiary teaching hospital, eligible patients were divided into two groups. Treatment group received duloxetine the day before initiation of chemotherapy regimen at a dose of 30 mg/day for one week and then, the dose was titrated up to 60 mg/day until 12 weeks. For placebo group, one placebo capsule was prescribed daily for one week followed by 2 capsules daily until 12 weeks. In each of chemotherapy courses, PN was assessed using national cancer institute-common terminology criteria for adverse effects (NCI-CTCAE v4.03). Also, chemotherapy -related QOL at the baseline and 12 weeks was assessed by functional assessment of cancer treatment gynecologic oncology group - neurotoxicity (FACT/GOG-NTX). Results Forty patients were randomly assigned to treatment and placebo groups which were similar to each other in terms of chemotherapy regimen, type, and stage of cancer. Analysis of results obtained from the NCI-CTCAE (v4.03) showed that duloxetine could prevent worsening of paresthesia more than placebo ( P = 0.025) and patients in duloxetine group experienced less peripheral sensory neuropathy ( P = 0.001) than placebo group. Analysis of results obtained from the FACT/GOG-NTX demonstrated a significant worsening of tingling and discomfort in hands ( P = 0.002, 0.001, respectively) and feet ( P = 0.017, 0.019, respectively) in placebo group compared to duloxetine group. Also, patients experienced more cold temperature -induced pain in extremities ( P = 0.001) in placebo group compared to duloxetine group. On the other hand, duloxetine could not improve QOL ( P = 0.06) and had not significant effects on trouble feeling the shape of small objects in hand ( P = 0.420) or trouble buttoning buttons ( P = 0.086). The P-value < 0.05 was considered to be statistically significant.
Self-Managed Music-Guided Exercise Intervention Improved Upper and Lower Extremity Muscle Strength for ICU Survivors—A Pilot Randomized Controlled Study
Authors: Liang Zhan , Yip Hilary , Sena Moore Kimberly , Ferreira Tanira , Ji Ming , Signorile Joseph F. , Munro Cindy 
Published: November 2021

Objective The objective of this study was to evaluate effects of a self-managed music-guided exercise intervention on muscle strength among intensive care unit (ICU) survivors. Methods We used a two-arm randomized-controlled trial. Following ICU discharge, eligible participants were assigned to one of two groups: music group ( n = 13) or active control group ( n = 13). The music group was taught to self-manage upper and lower extremity exercise movements by listening to an individualized music-guided playlist twice daily for 5 days. The active control group was provided an exercise brochure and advised to perform the same exercises at the same intervals. Dynamometers were used to measure muscle strength. T-tests and Weighted GEE models were used for testing the intervention effect between groups. Results Twenty-six subjects were enrolled. The mean age was 62.8 ( SD = 13.8), 53.8% were male, 65.4% were Caucasian, and the mean APACHE severity of illness score was 59 ( SD = 23.4). Reasons for ICU admission were mainly cardiac and medical. The music group showed significant improvements in handgrip, plantar flexion, leg extension, elbow flexion, and shoulder adduction strengths on left and right sides. Additionally, left and right leg extensor and left plantar flexor strengths showed significant post-differences, and small to moderately large effect sizes, between the music group and control group. Conclusion These findings suggest that a music-guided exercise intervention has the potential to improve muscle strength in ICU survivors and prevent further post-ICU deterioration in ICU survivors. Future trials should build upon these preliminary findings.
Increased Anti-Allergic Effects of Secretome of Low-Level Light Treated Tonsil-Derived Mesenchymal Stem Cells in Allergic Rhinitis Mouse Model
Authors: Park In-Su , Kim Dong-Kyu , Kim Ji Hye , Bae Jun-Sang , Kim Eun Hee , Yoo Shin Hyuk , Chung Young-Jun , Lyu Lele , Mo Ji-Hun 
Published: November 2021

Background Low-level light therapy (LLLT) is widely used for the photobiomodulation of cell behavior. Recent studies have shown that LLLT affects the proliferation and migration of various types of mesenchymal stem cells (MSCs). However, there is a lack of studies investigating the effect of LLT on enhancing the immunomodulatory properties of tonsil-derived MSCs (T-MSCs). Objective The aim of this study was to investigate the immunomodulatory effects of conditioned media from T-MSCs (T-MSCs-CM) treated with LLLT in allergic inflammation. Methods We isolated T-MSCs from human palatine tonsils and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM treated with LLLT was evaluated in a mouse model of allergic rhinitis (AR). We randomly divided the mice into four groups (negative control, positive control, T-MSCs-CM alone, and T-MSCs-CM treated with LLLT). To elucidate the therapeutic effect, we assessed rhinitis symptoms, serum immunoglobulin (Ig), the number of inflammatory cells, and cytokine expression. Results We identified increased expression of immunomodulatory factors, such as HGF, TGF-β, and PGE, in T-MSCs-CM treated with LLLT, compared to T-MSCs-CM without LLLT. Our animal study demonstrated reduced allergic symptoms and lower expression of total IgE and OVA-specific IgE in the LLLT-treated T-MSCs-CM group compared to the AR group and T-MSCs-CM alone. Moreover, we found that T-MSCs-CM treated with LLLT showed significantly decreased infiltration of eosinophils, neutrophils, and IL-17 cells in the nasal mucosa and reduced IL-4, IL-17, and IFN-γ expression in OVA-incubated splenocytes compared to the AR group. Conclusions The present study suggests that T-MSCs-CM treated with LLLT may provide an improved therapeutic effect against nasal allergic inflammation than T-MSCs-CM alone.
Biofeedback as an intervention for persistent post-concussive symptoms: A randomized feasibility trial
Authors: Bonn Marquise M , Alvarez Liliana , Graham Laura , Thompson James W , Dickey James P 
Published: November 2021

Background Case reports indicate that low-resolution electromagnetic tomography neurofeedback and heart rate variability biofeedback may improve physiological functioning in individuals with persistent post-concussive symptoms. However, it is unclear whether larger-scale studies are feasible. Purpose To evaluate the feasibility of a combined low-resolution electromagnetic tomography neurofeedback and heart rate variability biofeedback intervention for individuals with persistent post-concussive symptoms. Methods Individuals with persistent post-concussive symptoms were randomized into intervention and control groups, and their baseline and post-test assessments were compared to a healthy control group. Outcomes included self-report questionnaires, resting electroencephalograph and electrocardiograph recordings, and a driving simulation task. Participants in the intervention group completed three 20 min low-resolution electromagnetic tomography neurofeedback sessions per week and at-home heart rate variability biofeedback training every morning and night for 8 weeks. Feasibility was evaluated according to recruitment capability and sample characteristics, data collection procedures, suitability of the intervention and study procedures, management and implementation of the study intervention, and preliminary participant responses to the intervention. Results Thirty-three individuals were recruited and 24 completed this study (seven intervention participants, nine persistent post-concussive symptoms control participants, and eight healthy control participants). One-quarter of participants (four intervention participants and three persistent post-concussive symptoms control participants) experienced simulator sickness during the driving simulator task and had to withdraw from the study. Intervention participants had an 88% and 86% compliance rate for the low-resolution electromagnetic tomography neurofeedback and heart rate variability biofeedback sessions, respectively. Low-resolution electromagnetic tomography neurofeedback sessions took approximately 1 h to complete per participant. Preliminary analysis indicated that the intervention reduced electroencephalograph z-score deviation with a very large effect size ( d = 1.36) compared to the other study groups. Conclusions Pilot studies evaluating the efficacy of low-resolution electromagnetic tomography neurofeedback and heart rate variability biofeedback should be performed to confirm these preliminary findings. However, the protocol should be modified to reduce participant fatigue and withdrawal. This trial was registered with Clinicialtrials.gov (NCT03338036; https://clinicaltrials.gov/ct2/show/NCT03338036?term=03338036&draw=2&rank=1 ).
Postgraduate Students’ Experience of Using a Learning Management System to Support Their Learning: A Qualitative Descriptive Study
Authors: Steindal Simen A. , Ohnstad Mari O. , Landfald Ørjan Flygt , Solberg Marianne T. , Sørensen Anne Lene , Kaldheim Hege , Mathisen Cathrine , Christensen Vivi L. 
Published: November 2021

Introduction Educational institutions worldwide have implemented learning management systems (LMSs) to centralise and manage learning resources, educational services, learning activities and institutional information. LMS has mainly been used by teachers as storage and transfer of course material. To effectively utilise digital technologies in education, there is a need for more knowledge of student experiences with digital technology, such as LMSs and especially regarding how LMSs can contribute to student engagement and learning. Objective This study aimed to gain knowledge about postgraduate nursing students’ experiences with the use of LMS in a subject in an advanced practice nursing master's programme. Methods A qualitative method with a descriptive design was employed. Two focus group interviews were performed with eight postgraduate nursing students from an advanced practice nursing programme at a university college in Norway. Data were analysed using qualitative content analysis. Results Three themes emerged from the data material: 1) A course structure that supports learning; 2) LMS tools facilitate preparation, repetition and flexibility; and 3) own responsibility for using the LMS for preparation before on-campus activities. Conclusion The course structure within the LMS seemed to be important to enhance postgraduate students’ ability to prepare before on-campus activities. Implementation and use of LMS tools can facilitate preparation, repetition and flexibility, especially when postgraduate students study difficult topics. Postgraduate students seem to have different views regarding their own responsibility for using the LMS to prepare before on-campus activities.