bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charge reversal nano-systems for tumor therapy
Authors: Zhang Peng , Chen Daoyuan , Li Lin , Sun Kaoxiang 
Published: January 2022

AbstractSurface charge of biological and medical nanocarriers has been demonstrated to play an important role in cellular uptake. Owing to the unique physicochemical properties, charge-reversal delivery strategy has rapidly developed as a promising approach for drug delivery application, especially for cancer treatment. Charge-reversal nanocarriers are neutral/negatively charged at physiological conditions while could be triggered to positively charged by specific stimuli (i.e., pH, redox, ROS, enzyme, light or temperature) to achieve the prolonged blood circulation and enhanced tumor cellular uptake, thus to potentiate the antitumor effects of delivered therapeutic agents. In this review, we comprehensively summarized the recent advances of charge-reversal nanocarriers, including: (i) the effect of surface charge on cellular uptake; (ii) charge-conversion mechanisms responding to several specific stimuli; (iii) relation between the chemical structure and charge reversal activity; and (iv) polymeric materials that are commonly applied in the charge-reversal delivery systems.Graphical Abstract
Psychometric properties of self-reported measures of health-related quality of life in people living with HIV: a systematic review
Authors: Wen Huan , Yang Zhongfang , Zhu Zheng , Han Shuyu , Zhang Lin , Hu Yan 
Published: January 2022

Abstract
Objective
To identify and assess the psychometric properties of patient-reported outcome measures (PROMs) of health-related quality of life (HRQoL) in people living with HIV (PLWH).

Methods
Nine databases were searched from January 1996 to October 2020. Methodological quality was assessed by using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) Risk of Bias Checklist. We used the COSMIN criteria to summarize and rate the psychometric properties of each PROM. A modified Grading, Recommendations, Assessment, Development, and Evaluation (GRADE) system was used to assess the certainty of evidence.

Results
Sixty-nine studies reported on the psychometric properties of 30 identified instruments. All studies were considered to have adequate methodological quality in terms of content validity, construct validity, and internal consistency. Limited information was retrieved on cross-cultural validity, criterion validity, reliability, hypothesis testing, and responsiveness. High-quality evidence on psychometric properties was provided for the Medical Outcomes Study HIV Health Survey (MOS-HIV), the brief version of the World Health Organization's Quality of Life Instrument in HIV Infection (WHOQoL-HIV-BREF), 36-Item Short Form Survey (SF-36), Multidimensional Quality of Life Questionnaire for Persons with HIV/AIDS (MQoL-HIV), and WHOQoL-HIV.

Conclusions
The findings from the included studies highlighted that among HIV-specific and generic HRQoL PROMs, MOS-HIV, WHOQoL-HIV-BREF, SF-36, MQoL-HIV, and WHOQoL-HIV are strongly recommended to evaluate HRQoL in PLWH in research and clinics based on the specific aims of assessments and the response burden for participants.
Analysis of the psychometric properties of the Sense of Coherence scale (SOC-13) in patients with cardiovascular risk factors: a study of the method effects associated with negatively worded items
Authors: Domínguez-Salas Sara , Andrés-Villas Montserrat , Riera-Sampol Aina , Tauler Pedro , Bennasar-Veny Miquel , Aguilo Antoni , Rivera Francisco 
Published: January 2022

Abstract
Purpose
The objectives of this study were to analyze the psychometric properties of the Sense of Coherence scale (SOC-13), determine the role of the method effect in the performance of the instrument, and identify the relationship with health perception, quality of life, and sleep quality in patients at cardiovascular risk.

Methods
The final sample consisted of 293 patients at cardiovascular risk, with a mean age of 61.9 years (SD = 8.8), 49.8% of whom were women. The SOC-13, the Patient Health Questionnaire (PHQ-9), and the Medical Outcomes Study-Sleep Scale (MOS-Sleep) were administered. In addition, the participant's self-perceived health and quality of life were also evaluated. All analyses were carried out with SPSS 26.0 and EQS 6.1 statistical software.

Results
The results showed adequate reliability for the SOC-13, with a Cronbach's alpha of .789. The fit of the structures was not adequate in any of the cases (.26 to .62 for one factor, .26 to.73 for three factors, .20 to .54 for one second-order factor, and .25, .42, and .54 for three first-order factors). The three structure models showed an improved fit when adding a latent factor resulting from the method effect (.6 to .85 for one factor, .11 to.90 for three factors, and .11 to .96 for one second-order factor). Moreover, positive correlations were found with health perception, perceived quality of life, and perceived sleep quality.

Conclusion
The SOC-13 is a suitable instrument for patients with cardiovascular risk in Spain, and it is also an indicator of health perception, quality of life, and perceived quality of sleep. Control of the method effect improves the fit of the instrument’s structure. As a future direction, it is recommended to conduct new studies in this and other samples and using different versions of the SOC.

Trial registration

International Standard Randomized Controlled Trial Number: ISRCTN76069254, 08/04/2015 retrospectively registered.
Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis
Authors: Li Xiaoju , Su Shengtian , Ye Dan , Yu Zhigao , Lu Wenjing , Liu Liang 
Published: January 2022

Abstract
Background
Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown.

Methods
The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo.

Results
We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1.

Conclusion
Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.
A toolkit to rapidly modify root systems through single plant selection
Authors: Rambla Charlotte , Van Der Meer Sarah , Voss-Fels Kai P. , Makhoul Manar , Obermeier Christian , Snowdon Rod , Ober Eric S. , Watt Michelle , Alahmad Samir , Hickey Lee T. 
Published: January 2022

Abstract
Background
The incorporation of root traits into elite germplasm is typically a slow process. Thus, innovative approaches are required to accelerate research and pre-breeding programs targeting root traits to improve yield stability in different environments and soil types. Marker-assisted selection (MAS) can help to speed up the process by selecting key genes or quantitative trait loci (QTL) associated with root traits. However, this approach is limited due to the complex genetic control of root traits and the limited number of well-characterised large effect QTL. Coupling MAS with phenotyping could increase the reliability of selection. Here we present a useful framework to rapidly modify root traits in elite germplasm. In this wheat exemplar, a single plant selection (SPS) approach combined three main elements: phenotypic selection (in this case for seminal root angle); MAS using KASP markers (targeting a root biomass QTL); and speed breeding to accelerate each cycle.

Results
To develop a SPS approach that integrates non-destructive screening for seminal root angle and root biomass, two initial experiments were conducted. Firstly, we demonstrated that transplanting wheat seedlings from clear pots (for seminal root angle assessment) into sand pots (for root biomass assessment) did not impact the ability to differentiate genotypes with high and low root biomass. Secondly, we demonstrated that visual scores for root biomass were correlated with root dry weight (r = 0.72), indicating that single plants could be evaluated for root biomass in a non-destructive manner. To highlight the potential of the approach, we applied SPS in a backcrossing program which integrated MAS and speed breeding for the purpose of rapidly modifying the root system of elite bread wheat line Borlaug100. Bi-directional selection for root angle in segregating generations successfully shifted the mean root angle by 30° in the subsequent generation (P ≤ 0.05). Within 18 months, BC2F4:F5 introgression lines were developed that displayed a full range of root configurations, while retaining similar above-ground traits to the recurrent parent. Notably, the seminal root angle displayed by introgression lines varied more than 30° compared to the recurrent parent, resulting in lines with both narrow and wide root angles, and high and low root biomass phenotypes.

Conclusion
The SPS approach enables researchers and plant breeders to rapidly manipulate root traits of future crop varieties, which could help improve productivity in the face of increasing environmental fluctuations. The newly developed elite wheat lines with modified root traits provide valuable materials to study the value of different root systems to support yield in different environments and soil types.
Prognostic value of tumor measurement parameters and SCC-Ag changes in patients with locally-advanced cervical cancer
Authors: Chen Wenjuan , Xiu Siyi , Xie Xingyun , Guo Huiming , Xu Yuanji , Bai Penggang , Xia Xiaoyi 
Published: January 2022

Abstract
Objective
To investigate the prognostic relevance of specific measurement parameters such as tumor diameter, tumor volume, tumor volume reduction rate (TVRR), and changes in the squamous cell carcinoma antigen (SCC-Ag) level in patients with locally-advanced cervical cancer (LACC) undergoing concurrent radiotherapy and chemotherapy.

Methods
This was a retrospective study of 203 patients with stage IIA–IVA cervical squamous cell carcinoma who were newly diagnosed at our hospital between January 2011 and March 2015. Clinical data and pre-and post-treatment imaging information were collected and each parameter was calculated using 3DSlicer software. The pre/post-treatment tumor diameter (TDpre/post), tumor volume (TVpre/post), SCC-Ag (SCCpre/post), and TVRR, SCC-Ag reduction rate (SCCRR) were analyzed and their prognostic relevance evaluated.

Results
The median follow-up was 69 months. The 5-year overall survival (OS) and disease progression-free survival (PFS) rates were 69.5% and 64.5%, respectively. On univariate analysis, TDpre/post, TVpre/post, TVRR, SCCpre/post and SCCRR showed significant association with OS and PFS (P < 0.05). On multivariate analysis, TDpre [Hazard ratio (HR) = 0.373, P = 0.028], TDpost (HR = 0.376, P = 0.003) and SCCpost (HR = 0.374, P = 0.001) were independent predictors of OS. TVRR (HR = 2.998, P < 0.001), SCCpre (HR = 0.563, P = 0.041), and SCCpost (HR = 0.253, P < 0.001) were independent predictors of PFS. Tumor measurement parameters showed a positive correlation with SCC-Ag (P < 0.05).

Conclusion
TDpre/post, TVpre/post, TVRR, SCCpre/post, and SCCRR were prognostic factors in LACC. TDpre/post and SCCpost showed the most significant prognostic value. TVRR and SCCpre/post were closely related to disease progression. Further studies should investigate the correlation between measurement parameters of tumor and SCC-Ag.
Experienced fatigue in people with rare disorders: a scoping review on characteristics of existing research
Authors: Bathen Trine , Johansen Heidi , Strømme Hilde , Velvin Gry 
Published: January 2022

AbstractBackgroundExperienced fatigue is an under-recognized and under-researched feature in persons with many different rare diseases. A better overview of the characteristics of existing research on experienced fatigue in children and adults with rare diseases is needed. The purpose of this review was to map and describe characteristics of existing research on experienced fatigue in a selection of rare diseases in rare developmental defects or anomalies during embryogenesis and rare genetic diseases. Furthermore, to identify research gaps and point to research agendas.MethodsWe applied a scoping review methodology, and performed a systematic search in March 2020 in bibliographic databases. References were sorted and evaluated for inclusion using EndNote and Rayyan. Data were extracted on the main research questions concerning characteristics of research on experienced fatigue (definition and focus on fatigue, study populations, research questions investigated and methods used).ResultsThis review included 215 articles on ten different rare developmental defects/anomalies during embryogenesis and 35 rare genetic diseases. Of the 215 articles, 82 had investigation of experienced fatigue as primary aim or outcome. Included were 9 secondary research articles (reviews) and 206 primary research articles. A minority of articles included children. There were large differences in the number of studies in different diseases. Only 29 of 215 articles gave a description of how they defined the concept of experienced fatigue. The most common research-question reported on was prevalence and/ -or associations to fatigue. The least common was diagnostics (development or validation of fatigue assessment methods for a specific patient group). A large variety of methods were used to investigate experienced fatigue, impeding comparisons both within and across diagnoses.ConclusionThis scoping review on the characteristics of fatigue research in rare diseases found a large variety of research on experienced fatigue. However, the minority of studies had investigation of experienced fatigue as a primary aim. There was large variation in how experienced fatigue was defined and also in how it was measured, both within and across diagnoses. More research on experienced fatigue is needed, both in children and adults with rare diseases. This review offers a basis for further research.
A novel H129-based anterograde monosynaptic tracer exhibits features of strong labeling intensity, high tracing efficiency, and reduced retrograde labeling
Authors: Yang Hong , Xiong Feng , Qin Hai-Bin , Yu Qun-Tao , Sun Jin-Yan , Zhao Hai-Wen , Li Dong , Zhou Youtong , Zhang Fu-Kun , Zhu Xiao-Wen , Wu Tong , Jiang Man , Xu Xiangmin , Lu Youming , Shen Hong-Jie , Zeng Wen-Bo , Zhao Fei , Luo Min-Hua 
Published: January 2022

Abstract
Background
Viral tracers are important tools for mapping brain connectomes. The feature of predominant anterograde transneuronal transmission offers herpes simplex virus-1 (HSV-1) strain H129 (HSV1-H129) as a promising candidate to be developed as anterograde viral tracers. In our earlier studies, we developed H129-derived anterograde polysynaptic tracers and TK deficient (H129-dTK) monosynaptic tracers. However, their broad application is limited by some intrinsic drawbacks of the H129-dTK tracers, such as low labeling intensity due to TK deficiency and potential retrograde labeling caused by axon terminal invasion. The glycoprotein K (gK) of HSV-1 plays important roles in virus entry, egress, and virus-induced cell fusion. Its deficiency severely disables virus egress and spread, while only slightly limits viral genome replication and expression of viral proteins. Therefore, we created a novel H129-derived anterograde monosynaptic tracer (H129-dgK) by targeting gK, which overcomes the limitations of H129-dTK.

Methods
Using our established platform and pipeline for developing viral tracers, we generated a novel tracer by deleting the gK gene from the H129-G4. The gK-deleted virus (H129-dgK-G4) was reconstituted and propagated in the Vero cell expressing wildtype H129 gK (gKwt) or the mutant gK (gKmut, A40V, C82S, M223I, L224V, V309M), respectively. Then the obtained viral tracers of gKmut pseudotyped and gKwt coated H129-dgK-G4 were tested in vitro and in vivo to characterize their tracing properties.

Results
H129-dgK-G4 expresses high levels of fluorescent proteins, eliminating the requirement of immunostaining for imaging detection. Compared to the TK deficient monosynaptic tracer H129-dTK-G4, H129-dgK-G4 labeled neurons with 1.76-fold stronger fluorescence intensity, and visualized 2.00-fold more postsynaptic neurons in the downstream brain regions. gKmut pseudotyping leads to a 77% decrease in retrograde labeling by reducing axon terminal invasion, and thus dramatically improves the anterograde-specific tracing of H129-dgK-G4. In addition, assisted by the AAV helper trans-complementarily expressing gKwt, H129-dgK-G4 allows for mapping monosynaptic connections and quantifying the circuit connectivity difference in the Alzheimer’s disease and control mouse brains.

Conclusions
gKmut pseudotyped H129-dgK-G4, a novel anterograde monosynaptic tracer, overcomes the limitations of H129-dTK tracers, and demonstrates desirable features of strong labeling intensity, high tracing efficiency, and improved anterograde specificity.
Edaravone activates the GDNF/RET neurotrophic signaling pathway and protects mRNA-induced motor neurons from iPS cells
Authors: Li Qian , Feng Yi , Xue Yingchao , Zhan Xiping , Fu Yi , Gui Gege , Zhou Weiqiang , Richard Jean-Philippe , Taga Arens , Li Pan , Mao Xiaobo , Maragakis Nicholas J. , Ying Mingyao 
Published: January 2022

Abstract
Background
Spinal cord motor neurons (MNs) from human iPS cells (iPSCs) have wide applications in disease modeling and therapeutic development for amyotrophic lateral sclerosis (ALS) and other MN-associated neurodegenerative diseases. We need highly efficient MN differentiation strategies for generating iPSC-derived disease models that closely recapitulate the genetic and phenotypic complexity of ALS. An important application of these models is to understand molecular mechanisms of action of FDA-approved ALS drugs that only show modest clinical efficacy. Novel mechanistic insights will help us design optimal therapeutic strategies together with predictive biomarkers to achieve better efficacy.

Methods
We induce efficient MN differentiation from iPSCs in 4 days using synthetic mRNAs coding two transcription factors (Ngn2 and Olig2) with phosphosite modification. These MNs after extensive characterization were applied in electrophysiological and neurotoxicity assays as well as transcriptomic analysis, to study the neuroprotective effect and molecular mechanisms of edaravone, an FDA-approved drug for ALS, for improving its clinical efficacy.

Results
We generate highly pure and functional mRNA-induced MNs (miMNs) from control and ALS iPSCs, as well as embryonic stem cells. Edaravone alleviates H2O2-induced neurotoxicity and electrophysiological dysfunction in miMNs, demonstrating its neuroprotective effect that was also found in the glutamate-induced miMN neurotoxicity model. Guided by the transcriptomic analysis, we show a previously unrecognized effect of edaravone to induce the GDNF receptor RET and the GDNF/RET neurotrophic signaling in vitro and in vivo, suggesting a clinically translatable strategy to activate this key neuroprotective signaling. Notably, edaravone can replace required neurotrophic factors (BDNF and GDNF) to support long-term miMN survival and maturation, further supporting the neurotrophic function of edaravone-activated signaling. Furthermore, we show that edaravone and GDNF combined treatment more effectively protects miMNs from H2O2-induced neurotoxicity than single treatment, suggesting a potential combination strategy for ALS treatment.

Conclusions
This study provides methodology to facilitate iPSC differentiation and disease modeling. Our discoveries will facilitate the development of optimal edaravone-based therapies for ALS and potentially other neurodegenerative diseases.

Graphical abstract
Mammalian tumor-like organs. 1. The role of tumor-like normal organs and atypical tumor organs in the evolution of development (carcino-evo-devo)
Authors: Kozlov A. P. 
Published: January 2022

Abstract
Background
Earlier I hypothesized that hereditary tumors might participate in the evolution of multicellular organisms. I formulated the hypothesis of evolution by tumor neofunctionalization, which suggested that the evolutionary role of hereditary tumors might consist in supplying evolving multicellular organisms with extra cell masses for the expression of evolutionarily novel genes and the origin of new cell types, tissues, and organs. A new theory—the carcino-evo-devo theory—has been developed based on this hypothesis.

Main text
My lab has confirmed several non-trivial predictions of this theory. Another non-trivial prediction is that evolutionarily new organs if they originated from hereditary tumors or tumor-like structures, should recapitulate some tumor features in their development. This paper reviews the tumor-like features of evolutionarily novel organs. It turns out that evolutionarily new organs such as the eutherian placenta, mammary gland, prostate, the infantile human brain, and hoods of goldfishes indeed have many features of tumors. I suggested calling normal organs, which have many tumor features, the tumor-like organs.

Conclusion
Tumor-like organs might originate from hereditary atypical tumor organs and represent the part of carcino-evo-devo relationships, i.e., coevolution of normal and neoplastic development. During subsequent evolution, tumor-like organs may lose the features of tumors and the high incidence of cancer and become normal organs without (or with almost no) tumor features.