bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of carbon footprint and net ecosystem carbon budget under organic material retention combined with reduced mineral fertilizer
Authors: Liu Ying , Tang Haiying , Smith Pete , Zhong Chuan , Huang Guoqin 
Published: March 2021

Abstract
Background
Excessive application of chemical fertilizer has resulted in lower nitrogen uptake and utilization efficiency of crops, decreasing soil fertility, increasing greenhouse gas emissions, and worse environmental pollution. Organic material retention is regard as the key to solve these problems. The objective of this study is to conduct an assessment of carbon budget under Astragalus sinicus L. and rice straw retention combined with reduced mineral fertilizer based on the 2-year field experiment in a paddy field in the south of China. The experiment was randomized complete block design including four treatments with triplicates: control CK (winter follow, 120 kg ha−1 N fertilizer for each rice season) and three treatments with Astragalus sinicus L. and rice straw retention named RA, RB, and RC (reduced N fertilizer by 15%, 27.5%, and 40% in each rice season).

Results
Treatments RA, RB, and RC increased greenhouse gas emissions by 9.30–101.25%, among which CH4 accounted for more than 60%; Carbon input of crops from treatments RA, RB, and RC increased by 2.25–12.10% compared with control CK over the 2 years. Though treatments RA, RB, and RC enhanced CO2 emissions, treatment RB decreased carbon footprint and became carbon sink.

Conclusions
The results of this study reveal that treatment RB (Astragalus sinicus L. and rice straw retention with reduced N fertilizer by 27.5%) is better in reducing chemical fertilizer amount, increasing crop yield and carbon input, which is more conductive to sustainable development of agriculture.
Clinical and molecular characterization of patients with adenylosuccinate lyase deficiency
Authors: Mastrogiorgio Gerarda , Macchiaiolo Marina , Buonuomo Paola Sabrina , Bellacchio Emanuele , Bordi Matteo , Vecchio Davide , Brown Kari Payne , Watson Natalie Karen , Contardi Benedetta , Cecconi Francesco , Tartaglia Marco , Bartuli Andrea 
Published: March 2021

Abstract
Background
Adenylosuccinate lyase deficiency (ADSLD) is an ultrarare neurometabolic recessive disorder caused by loss-of-function mutations in the ADSL gene. The disease is characterized by wide clinical variability. Here we provide an updated clinical profiling of the disorder and discuss genotype–phenotype correlations.

Results
Data were collected through "Our Journey with ADSL deficiency Association" by using a dedicated web survey filled-in by parents.

Clinical and molecular data were collected from 18 patients (12 males, median age 10.9 years ± 7.3), from 13 unrelated families. The age at onset ranged from birth to the first three years (median age 0.63 years ± 0.84 SD), and age at diagnosis varied from 2 months to 17 years, (median age 6.4 years ± 6.1 SD). The first sign was a psychomotor delay in 8/18 patients, epilepsy in 3/18, psychomotor delay and epilepsy in 3/18, and apneas, hypotonia, nystagmus in single cases. One patient (sibling of a previously diagnosed child) had a presymptomatic diagnosis. The diagnosis was made by exome sequencing in 7/18 patients. All patients were definitively diagnosed with ADSL deficiency based on pathogenic variants and/or biochemical assessment. One patient had a fatal neonatal form of ADSL deficiency, seven showed features fitting type I, and nine were characterized by a milder condition (type II), with two showing a very mild phenotype. Eighteen different variants were distributed along the entire ADSL coding sequence and were predicted to have a variable structural impact by impairing proper homotetramerization or catalytic activity of the enzyme. Six variants had not previously been reported. All but two variants were missense.

Conclusions
The study adds more details on the spectrum of ADSLD patients’ phenotypes and molecular data.
TMEM52B suppression promotes cancer cell survival and invasion through modulating E-cadherin stability and EGFR activity
Authors: Lee Yunhee , Ko Dongjoon , Yoon Junghwa , Lee Younghoon , Kim Semi 
Published: March 2021

Abstract
Background
TMEM52B is a novel gene broadly expressed in a variety of normal human tissues. However, the biological function of TMEM52B expression in cancer is largely unknown.

Methods
The effects of TMEM52B on tumor growth and metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated. Clinical datasets from KmPlotter and The Cancer Genome Atlas (TCGA) were analyzed in relation to TMEM52B expression and function.

Results
Suppression of TMEM52B in colon cancer cells promoted cancer cell epithelial-mesenchymal transition (EMT), invasion, and survival in vitro. Similarly, in vivo studies showed increased tumor growth and circulating tumor cell survival (early metastasis). ERK1/2, JNK, and AKT signaling pathways were involved in TMEM52B suppression-induced invasiveness and cell survival. TMEM52B suppression promoted activation and internalization of epidermal growth factor receptor (EGFR) with enhanced downstream signaling activity, leading to enhanced cell survival and invasion. In addition, TMEM52B suppression reduced E-cadherin stability, likely due to a reduced association between it and E-cadherin, which led to enhanced β-catenin transcriptional activity. Concomitantly, TMEM52B suppression promoted generation of soluble E-cadherin fragments, contributing to the activation of EGFR. Clinical data showed that high TMEM52B expression correlated with increased patient survival in multiple types of cancer, including breast, lung, kidney, and rectal cancers, and suggested a correlation between TMEM52B and E-cadherin.

Conclusions
These findings suggest that TMEM52B is a novel modulator of the interplay between E-cadherin and EGFR. It is possible that TMEM52B functions as a tumor-suppressor that could potentially be used as a novel prognostic marker for cancer.
Single‐cell RNA sequencing in cancer research
Authors: Zhang Yijie , Wang Dan , Peng Miao , Tang Le , Ouyang Jiawei , Xiong Fang , Guo Can , Tang Yanyan , Zhou Yujuan , Liao Qianjin , Wu Xu , Wang Hui , Yu Jianjun , Li Yong , Li Xiaoling , Li Guiyuan , Zeng Zhaoyang , Tan Yixin , Xiong Wei 
Published: March 2021

AbstractSingle-cell RNA sequencing (scRNA-seq), a technology that analyzes transcriptomes of complex tissues at single-cell levels, can identify differential gene expression and epigenetic factors caused by mutations in unicellular genomes, as well as new cell-specific markers and cell types. scRNA-seq plays an important role in various aspects of tumor research. It reveals the heterogeneity of tumor cells and monitors the progress of tumor development, thereby preventing further cellular deterioration. Furthermore, the transcriptome analysis of immune cells in tumor tissue can be used to classify immune cells, their immune escape mechanisms and drug resistance mechanisms, and to develop effective clinical targeted therapies combined with immunotherapy. Moreover, this method enables the study of intercellular communication and the interaction of tumor cells and non-malignant cells to reveal their role in carcinogenesis. scRNA-seq provides new technical means for further development of tumor research and is expected to make significant breakthroughs in this field. This review focuses on the principles of scRNA-seq, with an emphasis on the application of scRNA-seq in tumor heterogeneity, pathogenesis, and treatment.
Overexpressed WDR3 induces the activation of Hippo pathway by interacting with GATA4 in pancreatic cancer
Authors: Su Wenjie , Zhu Shikai , Chen Kai , Yang Hongji , Tian Mingwu , Fu Qiang , Shi Ganggang , Feng Shijian , Ren Dianyun , Jin Xin , Yang Chong 
Published: March 2021

Abstract
Background
WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer.

Methods
The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions.

Results
Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion, and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, which interaction induced the nuclear translocation of GATA4 in pancreatic cancer cells.

Conclusions
We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through the interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.
Selinexor versus doxorubicin in dedifferentiated liposarcoma PDXs: evidence of greater activity and apoptotic response dependent on p53 nuclear accumulation and survivin down‐regulation
Authors: Zuco Valentina , Pasquali Sandro , Tortoreto Monica , Brich Silvia , Percio Stefano , Dagrada Gian Paolo , Colombo Chiara , Sanfilippo Roberta , Lauricella Calogero , Gounder Mrinal , El Bezawy Rihan , Barisella Marta , Dei Tos Angelo Paolo , Casali Paolo Giovanni , Gronchi Alessandro , Stacchiotti Silvia , Zaffaroni Nadia 
Published: March 2021

Abstract
Background
Dedifferentiated liposarcoma (DDLPS), a tumor that lacks effective treatment strategies and is associated with poor outcomes, expresses amplified MDM2 in the presence of wild-type p53. MDM2 ubiquitination of p53 facilitates its XPO1-mediated nuclear export, thus limiting p53 tumor suppressor functions. Consequently, nuclear export is a rational target in DDLPS. We directly compared the antitumor activity of the first-in class XPO1 inhibitor selinexor and doxorubicin, the standard front-line therapy in sarcomas, in DDLPS patient-derived xenografts (PDXs) and primary cell lines.

Methods
Drug activity was assessed in three PDXs (and two corresponding cell lines) established from the dedifferentiated component of primary untreated retroperitoneal DDLPS with myogenic (N = 2) and rhabdomyoblastic (N = 1) differentiation from patients who underwent surgery. These models were marked by amplification of MDM2, CDK4 and HMGA2 genes.

Results
Selinexor was moderately active in the three PDXs but achieved greater tumor response compared to doxorubicin (maximum tumor volume inhibition: 46–80 % vs. 37–60 %). The PDX harboring rhabdomyoblastic dedifferentiation showed the highest sensitivity to both agents. PDX response to selinexor and doxorubicin was not associated with the extent of MDM2 and CDK4 gene amplification. Interestingly, the most chemosensitive PDX model showed the lowest extent of HMGA2 amplification. Selinexor was also more efficient than doxorubicinin in inducing an apoptotic response in PDXs and cell lines. Consistently, an increased nuclear accumulation of p53 was seen in all selinexor-treated models. In addition, a time-dependent decrease of survivin expression, with an almost complete abrogation of the cytoplasmic anti-apoptotic pool of this protein, was observed as a consequence of the decreased acetylation/activation of STAT3 and the increased ubiquitination of nuclear survivin.

Conclusions
Selinexor showed a moderate antitumor activity in three DDLPS PDXs, which was, however, consistently higher than doxorubicin across all different models regardless the extent of MDM2 amplification and the histological differentiation. The depletion of survivin protein seems to significantly contribute to the induction of apoptosis through which selinexor exerts its antitumor activity.
An internet-based self-help intervention for people with psychological distress due to COVID-19: study protocol for a randomized controlled trial
Authors: Brog Noemi Anja , Hegy Julia Katharina , Berger Thomas , Znoj Hansjörg 
Published: March 2021

AbstractBackgroundThe coronavirus-19 (COVID-19) has reached pandemic status and is affecting countries all over the world. The COVID-19 pandemic is accompanied by various stressors that require adjustment in everyday life and possibly changes in personal future prospects. While some individuals cope well with these challenges, some develop psychological distress including depressive symptoms, anxiety, or stress. Internet-based self-help interventions have proven to be effective in the treatment of various mental disorders such as depression and anxiety. Based on that, we developed an internet-based self-help program for individuals with psychological distress due to the situation surrounding the COVID-19 pandemic. The 3-week self-help program consists of 6 modules comprising texts, videos, figures, and exercises. Participants can request guidance within the self-help program (guidance on demand). The primary aim of this study is to evaluate the efficacy and feasibility of the self-help program compared to a waiting control condition.MethodsThe design is a parallel group randomized controlled trial. Participants are allocated to a 3-week self-help intervention plus care as usual or a 3-week waiting period with only care as usual. There are follow-ups after 6 weeks and 18 weeks. At least 80 participants with COVID-19 pandemic related psychological distress will be recruited. Primary outcome are depressive symptoms. Secondary outcomes include anxiety and chronic stress, suicidal experiences and behavior, health-related quality of life, generalized optimism and pessimism, embitterment, optimistic self-beliefs, emotion regulation skills, loneliness, resilience, and the satisfaction with and usability of the self-help program.DiscussionTo the best of our knowledge, this is one of the first studies investigating the efficacy of an internet-based self-help program for psychological distress due to the situation surrounding the COVID-19 pandemic. Thus, the results of this study may give further insight into the use of internet-based self-help programs in pandemic-related psychological distress.Trial registrationClinicalTrials.govNCT04380909. Retrospectively registered on 8 May 2020.
Virtual reality stimulation to reduce the incidence of delirium in critically ill patients: study protocol for a randomized clinical trial
Authors: Naef Aileen C. , Jeitziner Marie-Madlen , Gerber Stephan M. , Jenni-Moser Béatrice , Müri René M. , Jakob Stephan M. , Nef Tobias , Hänggi Matthias 
Published: March 2021

Abstract
Background
Delirium has been long considered as a major contributor to cognitive impairments and increased mortality following a critical illness. Pharmacologic and non-pharmacologic strategies are used against delirium in the intensive care unit (ICU), despite these strategies remaining controversial. Previous studies have shown the feasibility of using virtual reality within the ICU setting, and we propose to use this technology to investigate the effect of immersive virtual reality stimulation on the incidence of delirium in the ICU. Moreover, we propose to use motion sensors to determine if patient movement patterns can lead to early prediction of delirium onset.

Methods
This study is conducted as a randomized clinical trial. A total of 920 critically ill patients in the ICU will participate. The control group will receive standard ICU care, whereas the intervention group will, in addition to the standard ICU care, receive relaxing 360-degree immersive virtual reality content played inside a head-mounted display with noise-cancelling headphones, three times a day. The first 100 patients, regardless of their group, will additionally have their movement patterns recorded using wearable and ambient sensors. Follow-up measurements will take place 6 months after discharge from the ICU.

Discussion
Delirium is widely present within the ICU setting but lacks validated prevention and treatment strategies. By providing patients with virtual reality stimulation presented inside a head-mounted display and noise-cancelling headphones, participants may be isolated from disturbances on an ICU. It is believed that by doing so, the incidence of delirium will be decrease among these patients. Moreover, identifying movement patterns associated with delirium would allow for early detection and intervention, which may further improve long-term negative outcomes associated with delirium during critical care.

Trial registration
ClinicalTrials.gov NCT04498585. Registered on August 3, 2020
Dropouts in randomized clinical trials of Korean medicine interventions: a systematic review and meta-analysis
Authors: Jeon Sae-rom , Nam Dongwoo , Kim Tae-Hun 
Published: March 2021

AbstractBackgroundThe dropout rate is an important determinant of outcomes in randomized controlled trials (RCTs) and should be carefully controlled. This study explored the current dropout rate in studies of Korean medicine (KM) interventions by systematic evaluation of RCTs conducted in the past 10 years.MethodsThree clinical trial registries (Clinical Research Information Service, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform) were searched to identify RCT protocols for KM interventions, such as acupuncture, herbal medicine, moxibustion, or cupping, and studies of mixed interventions, registered in Korea from 2009 to 2019. The PubMed, Embase, and OASIS databases were searched for the full reports of these RCTs, including published journal articles and theses. Dropout rates and the reasons for dropping out were analyzed in each report. The risk of bias in each of the included studies was assessed using the Cochrane risk of bias tool. The risk difference for dropping out between the treatment and control groups was calculated with the 95% confidence interval in a random effects model.ResultsForty-nine published studies were included in the review. The median dropout rate was 10% in the treatment group (interquartile range 6.7%, 17.0%) and 14% in the control group (interquartile range 5.4%, 16.3%) and was highest in acupuncture studies (12%), followed by herbal medicine (10%), moxibustion (8%), and cupping (7%). Loss to follow-up was the most common reason for dropping out. The risk difference for dropping out between the intervention and control groups was estimated to be 0.01 (95% confidence interval − 0.02, 0.03) in KM intervention studies.ConclusionsThis review found no significant difference in the dropout rate between studies according to the type of KM intervention. We recommend allowance for a minimum dropout rate of 15% in future RCTs of KM interventions.Review protocol registrationPROSPEROCRD42020141011
Blended cognitive behaviour therapy for children and adolescents with mitochondrial disease targeting fatigue (PowerMe): study protocol for a multiple baseline single case experiment
Authors: Klein I. L. , van de Loo K. F. E. , Hoogeboom T. J. , Janssen M. C. H. , Smeitink J. A. M. , van der Veer E. , Verhaak C. M. , Custers J. A. E. 
Published: March 2021

Abstract
Background
Mitochondrial disease is a rare, hereditary disease with a heterogeneous clinical presentation. However, fatigue is a common and burdensome complaint in children and adolescents with mitochondrial disease. No psychological intervention targeting fatigue exists for paediatric patients with a mitochondrial disease. We designed the PowerMe intervention, a blended cognitive behaviour therapy targeting fatigue in children and adolescents with mitochondrial disease. The aim of the intervention is to reduce perceived fatigue by targeting fatigue-related cognitions and behaviours.

Methods
A multiple baseline single case experiment will be conducted in five children (8–12 years old) and 5 adolescents (12–18 years old) with mitochondrial disease and severe fatigue. Patients will be included in the study for 33 weeks, answering weekly questions about the fatigue. Patients will be randomly assigned a baseline period of 5 to 9 weeks before starting the PowerMe intervention. The intervention consists of face-to-face and online sessions with a therapist and a website with information and assignments. The treatment will be tailored to the individual. Each patient will work on their personalized treatment plan focusing on personally relevant goals. The primary outcome is perceived fatigue. Secondary outcomes are quality of life, school presence and physical functioning.

Discussion
The results of the PowerMe study will provide information on the efficacy of a blended cognitive behaviour therapy on reducing perceived fatigue and its impact on daily life in children and adolescents with mitochondrial disease. Strengths and limitations of the study design are discussed.

Trial registration
Dutch Trial Register NTR 7675. Registered on 17 December 2018. Identifier https://www.trialregister.nl/trial/7433
Phenolics and related in vitro functional activities of different varieties of fresh waxy corn: a whole grain
Authors: Chen Lirong , Guo Yuqiu , Li Xiaoyue , Gong Kuijie , Liu Kaichang 
Published: March 2021

AbstractThe polyphenol distribution in fresh waxy corns of different color varieties and their functional activities, which may be useful for treating various chronic diseases, were investigated. The in vitro antioxidant activity, and hypoglycemic and hypocholesterolemic effects of the free and bound corn phenolics were determined to evaluate the edible value of fresh waxy corn. The colored varieties contained more phenols than the common varieties (white and/or yellow). The total free phenolic acid content of the six varieties was 6637.73 µg/g DW (dry weight), which was slightly higher (P > 0.05) than that of the total bound form (6276.65 µg/g DW). The total free flavonoid content was 5850.09 µg/g DW, which was higher (P < 0.05) than that of the total bound form (4874.51µg/g DW). No bound anthocyanin was detected in the methanol extracts of the tested varieties. For all the varieties, free polyphenols contributed 86−100 % and 70−78 % of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging abilities, respectively, and 100 % of the ferric reducing capacity. The free phenolics in fresh waxy corn showed better (P < 0.05) hypoglycemic effect than the bound form in terms of inhibition of α-amylase activity, whereas the bound phenolics of most varieties showed higher α-glucosidase inhibitory activity than the free forms. The free phenolics showed better (P < 0.05) glycocholesterol binding than the bound form for all varieties. The bound polyphenols showed better sodium cholate and taurocholate binding than the free form for most varieties. In conclusion, the difference between free and bound polyphenol content and functional activities indicates that fresh waxy corn can be potentially used for the development of functional food.