bluuebunny/crossref_metadata_2025_split huggingface dataset:
BZW2 Inhibition Reduces Colorectal Cancer Growth and Metastasis
Authors: Agarwal Sumit , Afaq Farrukh , Bajpai Prachi , Behring Michael , Kim Hyung-Gyoon , Varambally Amith , Chandrashekar Darshan S. , Peter Shajan , Diffalha Sameer Al , Khushman Moh'd , Seeber Andreas , Varambally Sooryanarayana , Manne Upender 
Published: April 2023

Abstract

Because survival of patients with metastatic colorectal cancer remain poor, there is an urgent need to identify potential novel druggable targets that are associated with colorectal cancer progression. One such target, basic leucine zipper and W2 domains 2 (BZW2), is involved in regulation of protein translation, and its overexpression is associated with human malignancy. Thus, we investigated the expression and regulation of BZW2, assessed its role in activation of WNT/β-catenin signaling, identified its downstream molecules, and demonstrated its involvement in metastasis of colorectal cancer. In human colorectal cancers, high mRNA and protein expression levels of BZW2 were associated with tumor progression. BZW2-knockdown reduced malignant phenotypes, including cell proliferation, invasion, and spheroid and colony formation. BZW2-knockdown also reduced tumor growth and metastasis; conversely, transfection of BZW2 into BZW2 low-expressing colorectal cancer cells promoted malignant features, including tumor growth and metastasis. BZW2 expression was coordinately regulated by microRNA-98, c-Myc, and histone methyltransferase enhancer of zeste homolog 2 (EZH2). RNA sequencing analyses of colorectal cancer cells modulated for BZW2 identified P4HA1 and the long noncoding RNAs, MALAT1 and NEAT1, as its downstream targets. Further, BZW2 activated the Wnt/β-catenin signaling pathway in colorectal cancers expressing wild-type β-catenin. In sum, our study suggests the possibility of targeting BZW2 expression by inhibiting EZH2 and/or c-Myc.

Implications:
FDA-approved small-molecule inhibitors of EZH2 can indirectly target BZW2 and because BZW2 functions as an oncogene, these inhibitors could serve as therapeutic agents for colorectal cancer.
METTL3-Mediated m6A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL
Authors: Wu Yiming , Jin Meiling , Fernandez Mike , Hart Kevyn L. , Liao Aijun , Ge Xinzhou , Fernandes Stacey M. , McDonald Tinisha , Chen Zhenhua , Röth Daniel , Ghoda Lucy Y. , Marcucci Guido , Kalkum Markus , Pillai Raju K. , Danilov Alexey V. , Li Jingyi Jessica , Chen Jianjun , Brown Jennifer R. , Rosen Steven T. , Siddiqi Tanya , Wang Lili 
Published: April 2023

Abstract

RNA splicing dysregulation underlies the onset and progression of cancers. In chronic lymphocytic leukemia (CLL), spliceosome mutations leading to aberrant splicing occur in ∼20% of patients. However, the mechanism for splicing defects in spliceosome-unmutated CLL cases remains elusive. Through an integrative transcriptomic and proteomic analysis, we discover that proteins involved in RNA splicing are posttranscriptionally upregulated in CLL cells, resulting in splicing dysregulation. The abundance of splicing complexes is an independent risk factor for poor prognosis. Moreover, increased splicing factor expression is highly correlated with the abundance of METTL3, an RNA methyltransferase that deposits N6-methyladenosine (m6A) on mRNA. METTL3 is essential for cell growth in vitro and in vivo and controls splicing factor protein expression in a methyltransferase-dependent manner through m6A modification-mediated ribosome recycling and decoding. Our results uncover METTL3-mediated m6A modification as a novel regulatory axis in driving splicing dysregulation and contributing to aggressive CLL.

Significance:
METTL3 controls widespread splicing factor abundance via translational control of m6A-modified mRNA, contributes to RNA splicing dysregulation and disease progression in CLL, and serves as a potential therapeutic target in aggressive CLL.
See related commentary by Janin and Esteller, p. 176.
This article is highlighted in the In This Issue feature, p. 171
Conhecimento fast track e orientação terapêutica: explorando as evidências relativas ao uso de inibidores do SRAA em pacientes hipertensos com COVID-19
Authors: Silva Filho Alberto Costa e , Silva Gabriel Oscar Santos da , Gouveia Luiz Fernando Fagundes , Vianna Paula Vilhena Carnevale 
Published: April 2023

Desde março de 2020, mais de 467 milhões de pessoas se contaminaram e 6,0 milhões faleceram em decorrência da Covid-19, até 17 de março de 2022. O conhecimento acerca da etiopatogenia do vírus, das medidas de prevenção da doença e de medidas terapêuticas evoluíram rapidamente. A comprovação de hipóteses experimentou novas formas de produção e divulgação de conhecimento, que incluíram as avaliações rápidas (fast track) de artigos científicos e plataformas de acesso aberto, divulgando produções não revistas por pares, o que contribuiu para a popularização da ciência. Neste cenário, circulam informações sem fundamentação científica, que tendem a gerar insegurança. Este ensaio, conduzido na forma de revisão narrativa, investiga um processo específico de geração e teste de hipótese, tendo como objeto a evolução do conhecimento acerca papel do sistema renina angiotensina aldosterona (SRAA), mais especificamente sobre a enzima conversora de angiotensina 2 (ECA2) e dos medicamentos que atuam sobre o SRAA, os inibidores da enzima conversora de angiotensina (IECA) e os bloqueadores dos receptores de angiotensina (BRA), na evolução clínica dos pacientes com COVID-19 e hipertensão. O sistema cardiovascular, em especial o SRAA, logo se mostrou relevante na Covid-19. Hipertensão é um fator de risco para gravidade e óbito por SARS-CoV-2 e a ECA2 é a porta de entrada para a invasão viral celular. Esses achados iniciais levaram à orientação de suspensão de medicamentos que atuam sobre o SRA, decisão questionada por especialistas e revista após a condução de estudos consistentes. Reafirma-se, diante de uma condição clínica nova e desafiadora, a importância da análise crítica da literatura científica e da clareza na comunicação pública dos achados, papel a ser desempenhado por um sistema de regulação ágil e fundamentado na ciência, em parceria com as sociedades de especialistas
Adherence to the EAT‐Lancet Healthy Reference Diet in Relation to Risk of Cardiovascular Events and Environmental Impact: Results From the EPIC‐NL Cohort
Authors: Colizzi Chiara , Harbers Marjolein C. , Vellinga Reina E. , Verschuren W. M. Monique , Boer Jolanda M. A. , Biesbroek Sander , Temme Elisabeth H. M. , van der Schouw Yvonne T. 
Published: April 2023

Background
The Healthy Reference Diet (HRD) was created to formulate dietary guidelines that would be healthy and sustainable. We aimed to construct a diet score measuring adherence to the HRD and to explore its association with cardiovascular events and environmental impact.

Methods and Results

We included 35 496 participants from the population‐based EPIC‐NL (European Prospective Investigation into Cancer and Nutrition‐Netherlands) study. HRD scores were calculated using data from food frequency questionnaires (0–140). Data on morbidity and mortality were retrieved through linkage with national and death registries. Data on environmental impact indicators were obtained from life cycle assessments. Associations between adherence to the HRD and cardiovascular events were estimated with Cox proportional hazard models. Linear regression analysis was conducted for the adherence to the HRD and each environmental indicator. High adherence to the HRD was associated with 14%, 12%, and 11% lower risks of cardiovascular disease (hazard ratio [HR]
Q4vsQ1
, 0.86 [95% CI, 0.78–0.94]), coronary heart disease (HR
Q4vsQ1
, 0.88 [95% CI, 0.78–1.00]), and total stroke (HR
Q4vsQ1
, 0.89 [95% CI, 0.72–1.10]), respectively. High HRD adherence was associated with 2.4% (95% CI, −5.0 to 0.2) lower greenhouse gas emissions, 3.9% (95% CI, −5.2 to −2.6) less land use, 0.5% (95% CI, −2.6 to 1.6), less freshwater eutrophication, 3.3% (95% CI, −5.8 to −0.8), less marine eutrophication, 7.7% (95% CI, −10.8 to −4.6), less terrestrial acidification, and 32.1 % (95% CI, 28.5–35.7) higher blue water use.

Conclusions
High adherence to the HRD was associated with lower risk of cardiovascular disease, coronary heart disease, and modestly lower levels of most environmental indicators but a higher level of blue water use.
Investigating the Applicability of a Global Average Calibration Line for Ambient Size-Resolved Cloud Condensation Nuclei (CCN) Measurements: A Technical Note
Authors: Salim Rizana , Singh Aishwarya , S Swetha , Kalkura Kavyashree N. , Gopinath Amar Krishna , Raj Subha S. , K. A. Rameshchand , Krishna R. Ravi , Gunthe Sachin S. 
Published: April 2023

Abstract
Aerosol–cloud–precipitation interaction represents the largest uncertainty in climate change’s current and future understanding. Therefore, aerosol properties affecting the cloud and precipitation formation and their accurate estimation is a first step in developing improved parameterizations for the prognostic climate models. Over the last couple of decades, a commercially available Cloud Condensation Nuclei Counter (CCNC) has been deployed in the field and laboratory for characterizing CCN properties of ambient or atmospherically relevant laboratory-generated aerosols. However, most of the CCN measurements performed in the field are often compounded with the erroneous estimation of CCN concentration and other parameters due to a lack of robust and accurate CCNC calibration. CCNC is not a plug-and-play instrument and requires prudent calibration and operation, to avoid erroneous data and added parameterization uncertainties. In this work, we propose and demonstrate the usability of a global calibration equation derived from CCNC calibration experiments from 8 contrasting global environments. Significant correlation was observed between the global calibration and each of the 16 individual experiments. A significant improvement in the correlation was observed when the calibration experiments were separated for high-altitude measurements. Using these equations, we further derived the effective hygroscopicity parameter and found lower relative uncertainty in the hygroscopicity parameter at higher effective supersaturation. Our results signify that altitude-based pressure change could be of importance for accurate calibration at high-altitude locations. Our results are consistent with previous studies emphasizing the criticality of the accurate CCN calibration for the lower supersaturations.
Lives Saved versus Time Lost: Direct Societal Benefits of Probabilistic Tornado Warnings
Authors: Ugarov Alexander 
Published: April 2023

Abstract
The National Weather Service is planning to implement the system of probabilistic tornado warnings. In this paper, I estimate and compare the full societal costs of tornadoes with existing deterministic and potential probabilistic warnings. These full costs include the value of statistical lives lost as well as the value of the time spent sheltering. I find that probabilistic tornado warnings would decrease total expected fatalities. The improvement in decision-making would also decrease the total opportunity cost of time spent sheltering, even though the total sheltering time is likely to increase. In total, probabilistic warnings should lower the societal costs of tornadoes relative to deterministic warnings by approximately $76–139 million per year, with a large portion of this improvement coming from fewer casualties.

Significance Statement
I measure societal benefits of probabilistic and deterministic tornado warnings in the United States by evaluating their effects on expected casualties and sheltering costs. I find that probabilistic warnings deliver almost twice as much net societal benefit as deterministic ones. These gains happen as a result of fewer casualties and making protective behavior more responsive to risks and sheltering costs. This paper provides additional evidence of the need to implement probabilistic extreme weather warnings.
Use of accelerometers in determining risk of falls in individuals post-stroke: A systematic review
Authors: Clark Elizabeth , Podschun Laura , Church Kelsie , Fleagle Aaron , Hull Paige , Ohree Samantha , Springfield Merebeth , Wood Shelby 
Published: April 2023

Objective The aim of this systematic review was to determine if the diagnostic capabilities of wearable accelerometers enhanced, provided earlier detection, or improved fall risk assessment when evaluating individuals with chronic stroke. Data sources CINAHL and PubMed databases were searched for articles from 2015 to 2023 utilizing key terms. Review methods A team of researchers reviewed articles for bias via the Quality in Prognostic Studies tool, and further analyzed the data to answer the research question. Results Four studies were included in the systematic review. When utilizing an accelerometer, the vertical axis was most predictive of falls, followed by the medio-lateral axis and the anterior-posterior axis. L2-3 was the most common accelerometer placement for fall risk assessment, however no uniformity existed in the literature on placement, number of accelerometers, or type. It was determined that gait symmetry, the Timed Up and Go, Berg Balance Scale, and Longitudinal Aging Study Amsterdam best predicted falls risk. Conclusion Based on limited available evidence, clinicians should continue to perform a comprehensive examination and evaluation for fall risk, that includes the use of a combination of evidence-based outcome measures and gait characteristics to develop an individualized plan of care for individuals post-stroke. However, further research is necessary to determine the added value of accelerometers as well as type, applicability of data, and placement.
Are 4D Motion Sensors Valid and Reliable for Studying Baseball Pitching?
Authors: Loushin Stacy R. , Verhoeven Martijn , Christoffer Daniel J. , Camp Christopher L. , Kaufman Kenton R. 
Published: April 2023

Background: Baseball pitching injuries are on the rise. Inertial measurement units (IMUs) provide immediate feedback to players and coaches, allowing for collection outside of the traditional laboratory setting with real-world application. The 4D Motion system provides kinematics throughout the pitching motion and may be beneficial for individualized programs in the throwing athlete. A systematic analysis of these sensors has not been completed. Purpose: To evaluate the validity of the 4D Motion IMU system for analyzing the baseball pitching motion compared with marker-based motion capture, and evaluate the internal reliability and consistency of the device. Study Design: Controlled laboratory study. Methods: Ten high school pitchers participated in this study (10 male; 9 right-hand dominant; mean age, 16.6 ± 1.3 years; mean body mass index, 24.1 ± 3.9). Participants were simultaneously outfitted with six 4D Motion IMU sensors and retroreflective markers. The pitchers threw fastballs at maximum effort off a mound at the standard height and distance. A comparison was made between the IMUs and corresponding motion capture values for shoulder external rotation, elbow flexion, chest extension, pelvis and chest rotation velocity, and rotation acceleration. Results: Significant differences were found for 5 of 7 metrics analyzed. The IMU overreported most metrics, except for elbow flexion and pelvis rotation angular acceleration, where both positive and negative errors were observed. The root mean square error and percentage errors indicated smaller discrepancies for chest extension (4°± 5°) and pelvis (38 ± 19 deg/s) and chest (96 ± 42 deg/s) rotation velocity, with elbow flexion having the largest variance (21°± 9°). Conclusion: The values of the 4D Motion IMU system should not be considered equivalent when compared with marker-based motion capture studies. The system lacked internal consistency and reliability, with angular velocities being the most consistent. Caution should be used when using the metrics provided by an IMU-based system for individualized monitoring. Clinical Relevance: If found valid and reliable, IMUs could be used for longitudinal workload monitoring, individualized throwing and rehabilitation programs, and ultimately injury prevention. This study demonstrates that the data obtained from a 4D Motion system using Gen 3 sensors are not equivalent to the data obtained from a marker-based motion capture system.
Psychological Distress and Anxiety among Nursing Professionals with Fear of Infection of COVID-19 Omicron Variant: A Cross Sectional E-survey Study
Authors: Pandey Ujjwal Kumar , Sharma Abhishek 
Published: April 2023

Background Contagious diseases are recognized as the most serious risks to population health. Even with the breakthroughs in medicine, there are still substantial causes of mortality and illness. During the early aftermath of the virus outbreak, the mental health of healthcare workers was severely impacted. Stress and anxiety appeared in the early stages of the pandemic, while symptoms of sadness, psychophysiological, and post-traumatic stress appeared later and remained for a long period, resulting in substantial repercussions. Aim To observe the psychological distress and anxiety among nursing professionals with fear of infection from COVID-19 omicron variant. Methods In this online cross-sectional survey study a self-made questionnaire was distributed to 246 nurses across the country using a snowball sampling method. Among 246 participants 210 were males and 36 were females between 18 and 38 years of age. Results The results of the study support the notion that the nursing professionals face psychological distress and anxiety due to the COVID-19 omicron variant. Conclusions The study was conducted on nursing professionals who were working in the COVID-19 ward and suffering from more psychological distress and anxiety.
Clinical Study of a Physician Modified Y-Type Iliac Branch Device (PMYIBD) in the Endovascular Repair of Abdominal Aortic Aneurysms to Preserve the Internal Iliac Artery
Authors: Zhao Zihe , Jin Yi , Fu Dongsheng , Liu Chen , Qiao Tong , Li Xiaoqiang , Gao Xia , Liu Zhao 
Published: April 2023

Objectives: To report the method and curative effect of using a physician modified Y-type iliac branch device (PMYIBD) to preserve the internal iliac artery during the endovascular repair of abdominal aortic aneurysms. Methods: From September 2018 to April 2022, 24 patients with abdominal aortic aneurysms or dissecting aneurysms, including 19 true aneurysms and 5 dissecting aneurysms involving the common iliac artery were treated in our department. The average age was (65.3 ± 7.6) years. All patients underwent preoperative evaluation by enhanced computed tomography. Combined with intraoperative angiography, a Y-type stent graft was prepared during surgery to perform endovascular repair of abdominal aortic aneurysms. Results: All operations were successfully completed. The average operative duration was (224.8 ± 44.1) minutes. A total of 24 internal iliac arteries were reconstructed. The average follow-up time was (27.1 ± 13.5) months. During the follow-up, there was no expansion of aneurysm cavity, no endoleak or stent displacement, and no death occurred in all patients. Discussion: The physician-modified Y-type iliac branched device (PMYIBD) provides an effective method for full-cavity repair. It has a wide range of indications and convenience. According to follow-up results, the early and mid-term had good curative effects; however, the long-term effects require further follow-up. Conclusion: The modified Y-type IBD technique is safe and effective for aortic diseases involving internal iliac artery especially with complex anatomy. Clinical Impact It is meaningful to preserve the IIA during EVAR. The use of PMYIBD provides a simple and effective method for the total endovascular repair of aortic diseases involving the IIA. Several advantages such as minimal trauma, low mortality, low complication rates and perfect short- and medium-term effects emerge in clinical practice. PMYIBDs are good choices for clinicians before suitable commercial stents are available in markets.
The Participation Experiences of Chinese Teacher Trainees and Their Finnish Teacher Trainer on an In-Service Teacher Training Program Exported From Finland to China
Authors: Peng (彭素豪) Suhao , Kantelinen Ritva , Räihä Pekka 
Published: April 2023

Purpose This paper aims to examine the participation experiences of a sample of Chinese teacher trainees and their Finnish teacher trainer on an in-service teacher training program exported from Finland to Beijing, China. Design/Approach/Methods Six science teachers from Beijing and their Finnish teacher trainer participated in semi-structured interviews. From the ideological perspective of international education, a total of eight semi-structured interviews were analyzed through qualitative content analysis. Findings The results show that all interviewees were highly motivated to learn from the Other's education system and culture. Some participants benefited from a broader understanding of the Self's and the Other's education systems, while others did not. The interviewees also described some participation challenges, such as language barriers and practices that adapted learner-centered teaching approaches in Beijing schools. Furthermore, the interviewees mentioned future expectations of more in-depth communication between Finland and China. Originality/Value Some recommendations for better training outcomes, improving the quality of participation experiences, and reaching more mutual understandings were discussed at the end of this study.
Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain
Authors: Breitinger Ulrike , Breitinger Hans-Georg 
Published: April 2023

AbstractPain, although unpleasant, is an essential warning mechanism against injury and damage of the organism. An intricate network of specialised sensors and transmission systems contributes to reception, transmission and central sensitization of pain. Here, we briefly introduce some of the main aspects of pain signal transmission, including nociceptors and nociceptive signals, mechanisms of inflammatory and neuropathic pain, and the situation of diabetes-associated neuropathic pain. The role of glia—astrocytes, microglia, satellite glia cells—and their specific channels, transporters and signaling pathways is described. A focus is on the contribution of inhibitory synaptic signaling to nociception and a possible role of glycine receptors in glucose-mediated analgesia and treatment-induced diabetic neuropathy. Inhibitory receptors such as GABAA- and glycine receptors are important contributors to nociceptive signaling; their contribution to altered pain sensation in diabetes may be of clinical relevance, and they could be promising therapeutic targets towards the development of novel analgesics.