bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic role of tumor size in stage T1 gastric cancer
Authors: Chen Yan , Jia Yukun , Peng Zhan , Wang Guangye 
Published: April 2022

Abstract
Background
The purpose was to assess the contribution of tumor size to the prognosis of patients with gastric cancer.

Methods
Patient data were sourced from the Surveillance, Epidemiology, and End Results program (SEER) database. Cox proportional risk regression was performed to determine the prognostic role of tumor size. Kaplan-Meier curves were conducted to calculate survival curves. Consistency index (c-index) and subject exercise curve (ROC) were utilized to assess the predictive ability of each factor on the prognosis of gastric cancer.

Results
Tumor size is preferable to other widely accepted prognostic clinical features in forecasting the survival of patients with gastric cancer.

Conclusions
The discriminatory ability of tumor size at T1 stage is superior to many other clinical prognostic factors.
Promoting an active choice among physically inactive adults: a randomised web-based four-arm experiment
Authors: Landais Lorraine L. , Damman Olga C. , Jelsma Judith G. M. , Verhagen Evert A. L. M. , Timmermans Danielle R. M. 
Published: April 2022

Abstract
Background
Promoting active (i.e., conscious, autonomous, informed, and value-congruent) choices may improve the effectiveness of physical activity interventions. This web-based four-arm experimental study investigated the effect of promoting an active versus passive choice regarding physical activity on behavioural and psychological outcomes (e.g., physical activity intentions and behaviours, autonomy, commitment) among physically inactive adults.

Methods
Dutch inactive adults were randomized into four groups: physical activity guideline only (control group G), guideline & information (GI), guideline & active choice (GA), or guideline & active choice & action planning (GA +). GA and GA + participants were stimulated to make an active choice by weighing advantages and disadvantages of physical activity, considering personal values, and identifying barriers. GA + participants additionally completed action/coping planning exercises. Passive choice groups G and GI did not receive exercises. Self-reported behavioural outcomes were assessed by a questionnaire pre-intervention (T0, n = 564) and at 2–4 weeks follow-up (T2, n = 493). Psychological outcomes were assessed post-intervention (T1, n = 564) and at follow-up. Regression analyses compared the outcomes of groups GI, GA and GA + with group G. We also conducted sensitivity analyses and a process evaluation.

Results
Although promoting an active choice process (i.e., interventions GA and GA +) did not improve intention (T1) or physical activity (T2 versus T0), GA + participants reported higher commitment at T1 (β = 0.44;95%CI:0.04;0.84) and more frequently perceived an increase in physical activity between T0 and T2 (β = 2.61;95%CI:1.44;7.72). GA participants also made a more active choice at T1 (β = 0.16;95%CI:0.04;0.27). The GA and GA + intervention did not significantly increase the remaining outcomes. GI participants reported higher intention strength (β = 0.64;95%CI:0.15;1.12), autonomy (β = 0.50;95%CI:0.05;0.95), and commitment (β = 0.39;95%CI:0.04;0.74), and made a more active choice at T1 (β = 0.13;95%CI:0.02;0.24). Interestingly, gender and health condition modified the effect on several outcomes. The GA + intervention was somewhat more effective in women. The process evaluation showed that participants varied in how they perceived the intervention.

Conclusions
There is no convincing evidence of a beneficial effect of an active versus passive choice intervention on physical activity intentions and behaviours among inactive adults. Further research should determine whether and how active choice interventions that are gender-sensitized and consider health conditions can effectively increase physical activity.

Trial registration
ClinicalTrials.gov: NCT04973813. Retrospectively registered.
The informal healthcare providers and universal health coverage in low and middle-income countries
Authors: Kumah Emmanuel 
Published: April 2022

AbstractThe World Health Organization has indicated that achieving universal health coverage (UHC) through public sector service delivery alone would not be possible. This calls for corporation, collaboration and partnership between the public and the private sector actors. Informal providers represent a significant portion of the healthcare delivery systems in low-and-middle-income countries (LMCs). However, the presence of this group of private sector actors in national health systems presents both challenges and opportunities. Considering the limited resources in LMCs, ignoring the role of the informal sector in national health systems is not an option. This paper aims to discuss the role of informal health care providers in achieving universal health coverage in low-and-middle-income countries.
Super-critical fluid extract of Bryonopsis laciniosa (Shivlingi) seeds restores fertility in zebrafish models through revival of cytological and anatomical features
Authors: Balkrishna Acharya , Nain Pradeep , Joshi Monali , Kumar Brijesh , Varshney Anurag 
Published: April 2022

Abstract
Background
The Ayurvedic system of medicine mentions the use of seeds of Bryonopsis laciniosa (L.) Naud. (also known as Shivlingi due to their unique structure resembling a ‘Shivling’) for treating sexual dysfunction, impaired fertility, and as a general virility-booster in both males and females. To investigate the scientific basis for such claims, the current study was designed for the chemical characterization of the super critical fluid extracted Shivlingi seed oil (SLSO), and subsequent evaluation of its reproductive fecundity in the zebrafish model of N-ethyl-N-nitrosourea induced infertility.

Results
Linoleic and linolenic acids were the major fatty acids in the SLSO, with trace amounts of β-sitosterol and stigmasterol. Both male and female zebrafish, when fed orally with the SLSO infused pallets, showed a dose-dependent increase in fertility and fecundity rates. Microscopic observations revealed recovery in the gross ovarian anatomy and consequential improvement in egg production in infertile female zebrafish. Similarly, cytological studies exhibited increased sperm counts and motility in male zebrafish. SLSO exhibited effects similar to the human equivalent dose of Letrozole.

Conclusion
Taken together, these observations demonstrated the fertility-boosting potentials of SLSO comparable to the widely used infertility drugs. As a whole, this research work has provided scientific evidence for the rationale behind the use of Shivlingi seeds in Ayurvedic treatment for infertility in humans. Finally, but importantly, this study warrants further scientific investigations into different aspects of SLSO on human reproductive health.
Measuring aniseikonia and investigating neuroplasticity and image factors in amblyopia (MAGNIFY): study protocol for a randomised clinical trial
Authors: South Jayshree , Gao Tina , Calderwood Melinda , Turuwhenua Jason , Roberts Paul , Lee Arier , Collins Andrew , Black Joanna 
Published: April 2022

Abstract
Background
Aniseikonia represents a potential barrier to neuroplasticity which may limit visual outcomes in children with anisometropic amblyopia. Full correction of refractive error is the first step in standard amblyopia treatment, which corrects for image focus but neglects image size differences.

Methods
The MAGNIFY study is a double-masked, randomised clinical trial investigating the effectiveness of aniseikonia correcting lenses in children at first diagnosis of significant anisometropia. We hypothesis that aniseikonia correction lenses will improve image clarity and reduce the retinal size differences producing better visual acuity and stereoacuity improvements after 15 weeks of optical treatment for children with anisometropia. Eligible children will be randomly allocated to the treatment group (aniseikonia-correcting spectacle lenses) or control group (standard spectacle lenses). Visual acuity and binocular functions will be assessed every 5 weeks during the 15-week optical treatment phase according to standard amblyopia treatment protocol.

Discussion
It is possible that correcting aniseikonia along with anisometropia at first diagnosis will promote binocularity as well as increase spectacle adherence by reducing visual discomfort, improving optical treatment outcomes. This could then reduce the need for additional amblyopia treatment such as patching or atropine, reducing the burden on hospital eye departments and potentially improving visual outcomes for children with amblyopia.

Trial registration
Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000061932. Registered on 24 January 2020. Protocol 15th November 2019, version one.
Fleshy or dry: transcriptome analyses reveal the genetic mechanisms underlying bract development in Ephedra
Authors: Zumajo-Cardona Cecilia , Ambrose Barbara A. 
Published: April 2022

Abstract
Background
Gnetales have a key phylogenetic position in the evolution of seed plants. Among the Gnetales, there is an extraordinary morphological diversity of seeds, the genus Ephedra, in particular, exhibits fleshy, coriaceous or winged (dry) seeds. Despite this striking diversity, its underlying genetic mechanisms remain poorly understood due to the limited studies in gymnosperms. Expanding the genomic and developmental data from gymnosperms contributes to a better understanding of seed evolution and development.

Results
We performed transcriptome analyses on different plant tissues of two Ephedra species with different seed morphologies. Anatomical observations in early developing ovules, show that differences in the seed morphologies are established early in their development. The transcriptomic analyses in dry-seeded Ephedra californica and fleshy-seeded Ephedra antisyphilitica, allowed us to identify the major differences between the differentially expressed genes in these species. We detected several genes known to be involved in fruit ripening as upregulated in the fleshy seed of Ephedra antisyphilitica.

Conclusions
This study allowed us to determine the differentially expressed genes involved in seed development of two Ephedra species. Furthermore, the results of this study of seeds with the enigmatic morphology in Ephedra californica and Ephedra antisyphilitica, allowed us to corroborate the hypothesis which suggest that the extra envelopes covering the seeds of Gnetales are not genetically similar to integument. Our results highlight the importance of carrying out studies on less explored species such as gymnosperms, to gain a better understanding of the evolutionary history of plants.
MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against diabetic nephropathy in rats through facilitating M2 macrophage polarization
Authors: Zhang Yaqi , Le Xi , Zheng Shuo , Zhang Ke , He Jing , Liu Mengting , Tu Chengshu , Rao Wei , Du Hongyuan , Ouyang Yu , Li Changyong , Wu Dongcheng 
Published: April 2022

AbstractBackgroundDiabetic nephropathy (DN) is a severe complication of diabetes mellitus and a common cause of end-stage renal disease (ESRD). Mesenchymal stem cells (MSCs) possess potent anti-inflammatory and immunomodulatory properties, which render them an attractive therapeutic tool for tissue damage and inflammation.MethodsThis study was designed to determine the protective effects and underlying mechanisms of human umbilical cord-derived MSCs (UC-MSCs) on streptozotocin-induced DN. Renal function and histological staining were used to evaluate kidney damage. RNA high-throughput sequencing on rat kidney and UCMSC-derived exosomes was used to identify the critical miRNAs. Co-cultivation of macrophage cell lines and UC-MSCs-derived conditional medium were used to assess the involvement of macrophage polarization signaling.ResultsUC-MSC administration significantly improved renal function, reduced the local and systemic inflammatory cytokine levels, and attenuated inflammatory cell infiltration into the kidney tissue in DN rats. Moreover, UC-MSCs shifted macrophage polarization from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. Mechanistically, miR-146a-5p was significantly downregulated and negatively correlated with renal injury in DN rats as determined through high-throughput RNA sequencing. Importantly, UC-MSCs-derived miR-146a-5p promoted M2 macrophage polarization by inhibiting tumor necrosis factor receptor-associated factor-6 (TRAF6)/signal transducer and activator of transcription (STAT1) signaling pathway. Furthermore, miR-146a-5p modification in UC-MSCs enhanced the efficacy of anti-inflammation and renal function improvement.ConclusionsCollectively, our findings demonstrate that UC-MSCs-derived miR-146a-5p have the potential to restore renal function in DN rats through facilitating M2 macrophage polarization by targeting TRAF6. This would pave the way for the use of miRNA-modified cell therapy for kidney diseases.
PTEN mutant non-small cell lung cancer require ATM to suppress pro-apoptotic signalling and evade radiotherapy
Authors: Fischer Thomas , Hartmann Oliver , Reissland Michaela , Prieto-Garcia Cristian , Klann Kevin , Pahor Nikolett , Schülein-Völk Christina , Baluapuri Apoorva , Polat Bülent , Abazari Arya , Gerhard-Hartmann Elena , Kopp Hans-Georg , Essmann Frank , Rosenfeldt Mathias , Münch Christian , Flentje Michael , Diefenbacher Markus E. 
Published: April 2022

Abstract
Background
Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy.

Results
We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model.

Conclusion
PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.
Pharmacological activation of ATF6 remodels the proteostasis network to rescue pathogenic GABAA receptors
Authors: Wang Meng , Cotter Edmund , Wang Ya-Juan , Fu Xu , Whittsette Angela L. , Lynch Joseph W. , Wiseman R. Luke , Kelly Jeffery W. , Keramidas Angelo , Mu Ting-Wei 
Published: April 2022

Abstract
Background
Genetic variants in the subunits of the gamma-aminobutyric acid type A (GABAA) receptors are implicated in the onset of multiple pathologic conditions including genetic epilepsy. Previous work showed that pathogenic GABAA subunits promote misfolding and inefficient assembly of the GABAA receptors, limiting receptor expression and activity at the plasma membrane. However, GABAA receptors containing variant subunits can retain activity, indicating that enhancing the folding, assembly, and trafficking of these variant receptors offers a potential opportunity to mitigate pathology associated with genetic epilepsy.

Results
Here, we demonstrate that pharmacologically enhancing endoplasmic reticulum (ER) proteostasis using small molecule activators of the ATF6 (Activating Transcription Factor 6) signaling arm of the unfolded protein response (UPR) increases the assembly, trafficking, and surface expression of variant GABAA receptors. These improvements are attributed to ATF6-dependent remodeling of the ER proteostasis environment, which increases protein levels of pro-folding ER proteostasis factors including the ER chaperone BiP (Immunoglobulin Binding Protein) and trafficking receptors, such as LMAN1 (Lectin Mannose-Binding 1) and enhances their interactions with GABAA receptors. Importantly, we further show that pharmacologic ATF6 activators increase the activity of GABAA receptors at the cell surface, revealing the potential for this strategy to restore receptor activity to levels that could mitigate disease pathogenesis.

Conclusions
These results indicate that pharmacologic ATF6 activators offer an opportunity to restore GABAA receptor activity in diseases including genetic epilepsy and point to the potential for similar pharmacologic enhancement of ER proteostasis to improve trafficking of other disease-associated variant ion channels implicated in etiologically-diverse diseases.
Effectiveness of mindfulness-based interventions on well-being and work-related stress in the financial sector: a systematic review and meta-analysis protocol
Authors: Dinesh Tantri Keerthi , Shetty Ankitha , Dhyani Vijay Shree , T.S Shwetha , Dsouza Komal Jenifer 
Published: April 2022

Abstract
Background
Work-related stress is a common phenomenon, often noticed in the employees of the finance sector. It mirrors counter effects on the wellness of employees, their mental well-being, and physical health. Mindfulness-based interventions (MBIs) raise awareness and attention to the present moment experiences by adopting coping skills. It is necessary to promote employee well-being and reduce work-related stress; hence, the need arises to associate between the level of mindfulness, employee well-being, and work-related stress. A systematic review on the effectiveness of MBIs in the finance sector is necessary to facilitate evidence for the future utility to reduce work-related stress and promote employee well-being.

Methods
In this review, randomized controlled trials, non-randomized control trials, cohort, and cross-sectional and case-control studies that assess the effectiveness of MBIs on the employees in the finance sector will be considered. We propose to perform a literature search which will be conducted from the years 2000 to 2021 on CINAHL, Cochrane Library, ProQuest, PubMed, Scopus, and Web of Science. The search terms will include controlled and accessible terms such as mindfulness-based interventions, mindfulness training, workplace, employees, workers, well-being, employee wellness, occupational health, and finance sector. The outcomes will include the effect on employee well-being and reduction in work-related stress. Two researchers will independently conduct the screening and data extraction and assess the risk of bias. Based on the availability of data, a meta-analysis will also be performed. This protocol follows the Preferred Reporting Items for Systematic reviews and Meta-Analysis-Protocol (PRISMA-P) guidelines. “Assessing the Methodological Quality of Systematic Reviews” will be used to assess the quality of this review.

Discussion
The review attempts to methodically analyse the effectiveness of MBIs among finance sector employees. It will foster to facilitate a detailed description and evidence-based overview of the effectiveness of MBIs on improving work-related stress, mindful awareness, and employee wellness and well-being in employees in the finance sector. The current study will provide an evidence base to researchers, academicians, and practitioners in the selection of mindfulness-based therapies for employees in the finance sector.

Systematic review registration
PROSPERO 2021 CRD42021249782
The multivariate analysis of variance as a powerful approach for circular data
Authors: Landler Lukas , Ruxton Graeme D. , Malkemper E. Pascal 
Published: April 2022

AbstractBackgroundA broad range of scientific studies involve taking measurements on a circular, rather than linear, scale (often variables related to times or orientations). For linear measures there is a well-established statistical toolkit based on linear modelling to explore the associations between this focal variable and potentially several explanatory factors and covariates. In contrast, statistical testing of circular data is much simpler, often involving either testing whether variation in the focal measurements departs from circular uniformity, or whether a single explanatory factor with two levels is supported.MethodsWe use simulations and example data sets to investigate the usefulness of a MANOVA approach for circular data in comparison to commonly used statistical tests.ResultsHere we demonstrate that a MANOVA approach based on the sines and cosines of the circular data is as powerful as the most-commonly used tests when testing deviation from a uniform distribution, while additionally offering extension to multi-factorial modelling that these conventional circular statistical tests do not.ConclusionsThe herein presented MANOVA approach offers a substantial broadening of the scientific questions that can be addressed statistically using circular data.
Space-to-space very low frequency radio transmission in the magnetosphere using the DSX and Arase satellites
Authors: McCollough James P. , Miyoshi Yoshizumi , Ginet Gregory P. , Johnston William R. , Su Yi-Jiun , Starks Michael J. , Kasahara Yoshiya , Kojima Hirotsugu , Matsuda Shoya , Shinohara Iku , Song Paul , Reinisch Bodo W. , Galkin Ivan A. , Inan Umran S. , Lauben David S. , Linscott Ivan , Ling Alan G. , Allgeier Shawn , Lambour Richard , Schoenberg Jon , Gillespie William , Stelmash Stephen , Roche Kevin , Sinclair Andrew J. , Sanchez Jenny C. , Pedinotti Gregory F. , Langhals Jarred T. 
Published: April 2022

AbstractVery low frequency (VLF) waves (about 3–30 kHz) in the Earth’s magnetosphere interact strongly with energetic electrons and are a key element in controlling dynamics of the Van Allen radiation belts. Bistatic very low frequency (VLF) transmission experiments have recently been conducted in the magnetosphere using the high-power VLF transmitter on the Air Force Research Laboratory’s Demonstration and Science Experiments (DSX) spacecraft and an electric field receiver onboard the Japan Aerospace Exploration Agency’s Arase (ERG) spacecraft. On 4 September 2019, the spacecraft came within 410 km of each other and were in geomagnetic alignment. During this time, VLF signals were successfully transmitted from DSX to Arase, marking the first successful reception of a space-to-space VLF signal. Arase measurements were consistent with field-aligned propagation as expected from linear cold plasma theory. Details of the transmission event and comparison to VLF propagation model predictions are presented. The capability to directly inject VLF waves into near-Earth space provides a new way to study the dynamics of the radiation belts, ushering in a new era of space experimentation.
Graphical Abstract