bluuebunny/crossref_metadata_2025 huggingface dataset:
A systems approach to scale-up for population health improvement
Authors: Koorts Harriet , Rutter Harry
Published: March 2021

Despite a number of important global public health successes, for many health behaviours there is a continued lack of interventions that have been sufficiently scaled up to achieve system-wide integration. This has limited sustainable and equitable population health improvement. Systems change plays a major role in the relation between implementation processes and at-scale institutionalisation of public health interventions. However, in research, systems approaches remain underutilised in scaling up. Public health scale-up models have typically centred on intervention replication through linear expansion. In this paper, we discuss current conceptualisations and approaches used when scaling up in public health, and propose a new perspective on scaling that shifts attention away from the intervention to focus instead on achieving the desired population-level health outcomes. In our view, ‘scaling up’ exists on a continuum. At one end, effective scaling can involve a linear, intervention-orientated expansive approach that prioritises the spread of evidence-based interventions into existing systems in order to drive expansion in the application of that intervention. At the other end, we contend that scale-up can sit within a complex systems paradigm in which interventions are conceptualised as events in systems. In this case, implementation and scale-up activities should focus on generating changes within the system itself to achieve the desired outcome. This we refer to as ‘systems-orientated scale-up’ to achieving population health improvement, which can complement traditional approaches in relevant situations. We argue that for some health behaviours, our proposed approach towards scaling up could enhance intervention implementation, sustainability and population health impact.
Recombinant CCL17-dependent CCR4 activation alleviates neuroinflammation and neuronal apoptosis through the PI3K/AKT/Foxo1 signaling pathway after ICH in mice
Authors: Deng Shuixiang , Jin Peng , Sherchan Prativa , Liu Shengpeng , Cui Yuhui , Huang Lei , Zhang John H. , Gong Ye , Tang Jiping
Published: March 2021

Background

Intracerebral hemorrhage (ICH), a devastating subtype of stroke, is associated with high mortality and morbidity. Neuroinflammation is an important factor leading to ICH-induced neurological injuries. C-C Chemokine Receptor 4 (CCR4) plays an important role in enhancing hematoma clearance after ICH. However, it is unclear whether CCR4 activation can ameliorate neuroinflammation and apoptosis of neurons following ICH. The aim of the present study was to examine the effects of recombinant CCL17 (rCCL17)-dependent CCR4 activation on neuroinflammation and neuronal apoptosis in an intrastriatal autologous blood injection ICH model, and to determine whether the PI3K/AKT/Foxo1 signaling pathway was involved.

Methods

Two hundred twenty-six adult (8-week-old) male CD1 mice were randomly assigned to sham and ICH surgery groups. An intrastriatal autologous blood injection ICH model was used. rCCL17, a CCR4 ligand, was delivered by intranasal administration at 1 h, 3 h, and 6 h post-ICH. CCL17 antibody was administrated by intraventricular injection at 1 h post-ICH. C021, a specific inhibitor of CCR4 and GDC0068, an AKT inhibitor were delivered intraperitoneally 1 h prior to ICH induction. Brain edema, neurobehavioral assessments, western blotting, Fluoro-Jade C staining, terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunofluorescence staining were conducted.

Results

Endogenous expression of CCL17 and CCR4 were increased following ICH, peaking at 5 days post-induction. CCR4 was found to co-localize with microglia, neurons, and astrocytes. rCCL17 treatment decreased brain water content, attenuated short- and long-term neurological deficits, deceased activation of microglia/macrophages and infiltration of neutrophils, and inhibited neuronal apoptosis in the perihematomal region post-ICH. Moreover, rCCL17 treatment post-ICH significantly increased the expression of CCR4, PI3K, phosphorylated AKT, and Bcl-2, while Foxo1, IL-1β, TNF-α, and Bax expression were decreased. The neuroprotective effects of rCCL17 were reversed with the administration of C021 or GDC0068.

Conclusions

rCCL17-dependent CCR4 activation ameliorated neurological deficits, reduced brain edema, and ameliorated neuroinflammation and neuronal apoptosis, at least in part, through the PI3K/AKT/Foxo1 signaling pathway after ICH. Thus, activation of CCR4 may provide a promising therapeutic approach for the early management of ICH.
Women’s sleep position during pregnancy in low- and middle-income countries: a systematic review
Authors: Rossiter Shania K. , Aziz Samia , Wilson Alyce N. , Comrie-Thomson Liz , Stacey Tomasina , Homer Caroline S. E. , Vogel Joshua P.
Published: March 2021

Background

Approximately 2.6 million babies are stillborn each year globally, of which 98% occur in low- and middle-income countries (LMICs). A 2019 individual participant data meta-analysis of 6 studies from high-income countries found that maternal supine going-to-sleep position increased the risk of stillbirth. It is not clear whether this impact would be the same in LMICs, and the normal sleep behaviour of pregnant women in LMICs is not well understood.

Objective

Determine the prevalence of different sleeping positions among pregnant women in LMICs, and what (if any) positions were associated with stillbirth using a systematic review.

Search strategy

We systematically searched the databases Medline, Embase, Emcare, CINAHL and Global Index Medicus for relevant studies, with no date or language restrictions on 4 April 2020. Reference lists of included studies were also screened.

Selection criteria

Observational studies of maternal sleep position during pregnancy in LMICs

Data collection and analysis

Recovered citations were screened and eligible studies were included for extraction. These steps were performed by two independent reviewers. Risk of bias was assessed using the Newcastle–Ottawa Scale.

Main results

A total of 3480 citations were screened but only two studies met the inclusion criteria. The studies were conducted in Ghana and India and reported on different maternal sleep positions: supine and left lateral. In Ghana, a prevalence of 9.7% for supine sleeping position amongst 220 women was found. The primary outcome could not be extracted from the Indian study as sleep position information was only reported for women who had a stillbirth (100 of the 300 participants).

Conclusion

There is limited information on maternal sleeping position in LMICs. Since sleep position may be a modifiable risk factor for stillbirth, there is a need for further research to understand the sleep practices and behaviours of pregnant women in LMICs.

PROSPERO registration: CRD42020173314
HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7
Authors: Zhou Xiaohong , Monnie Christina , DeLucia Maria , Ahn Jinwoo
Published: March 2021

Background

Vpr is a virion-associated protein that is encoded by lentiviruses and serves to counteract intrinsic immunity factors that restrict infection. HIV-1 Vpr mediates proteasome-dependent degradation of several DNA repair/modification proteins. Mechanistically, Vpr directly recruits cellular targets onto DCAF1, a substrate receptor of Cullin 4 RING E3 ubiquitin ligase (CRL4) for poly-ubiquitination. Further, Vpr can mediate poly-ubiquitination of DCAF1-interacting proteins by the CRL4. Because Vpr-mediated degradation of its known targets can not explain the primary cell-cycle arrest phenotype that Vpr expression induces, we surveyed the literature for DNA-repair-associated proteins that interact with the CRL4-DCAF1. One such protein is SIRT7, a deacetylase of histone 3 that belongs to the Sirtuin family and regulates a wide range of cellular processes. We wondered whether Vpr can mediate degradation of SIRT7 via the CRL4-DCAF1.

Methods

HEK293T cells were transfected with cocktails of plasmids expressing DCAF1, DDB1, SIRT7 and Vpr. Ectopic and endogeneous levels of SIRT7 were monitered by immunoblotting and protein–protein interactions were assessed by immunoprecipitation. For in vitro reconstitution assays, recombinant CRL4-DCAF1-Vpr complexes and SIRT7 were prepared and poly-ubiqutination of SIRT7 was monitored with immunoblotting.

Results

We demonstrate SIRT7 polyubiquitination and degradation upon Vpr expression. Specifically, SIRT7 is shown to interact with the CRL4-DCAF1 complex, and expression of Vpr in HEK293T cells results in SIRT7 degradation, which is partially rescued by CRL inhibitor MNL4924 and proteasome inhibitor MG132. Further, in vitro reconstitution assays show that Vpr induces poly-ubiquitination of SIRT7 by the CRL4-DCAF1. Importantly, we find that Vpr from several different HIV-1 strains, but not HIV-2 strains, mediates SIRT7 poly-ubiquitination in the reconstitution assay and degradation in cells. Finally, we show that SIRT7 degradation by Vpr is independent of the known, distinctive phenotype of Vpr-induced cell cycle arrest at the G2 phase,

Conclusions

Targeting histone deacetylase SIRT7 for degradation is a conserved feature of HIV-1 Vpr. Altogether,our findings reveal that HIV-1 Vpr mediates down-regulation of SIRT7 by a mechanism that does not involve novel target recruitment to the CRL4-DCAF1 but instead involves regulation of the E3 ligase activity.
Dramatic increase in water use efficiency with cumulative forest disturbance at the large forested watershed scale
Authors: Giles-Hansen Krysta , Wei Xiaohua , Hou Yiping
Published: March 2021

Background

Forest disturbance induced changes in the coupling of forest carbon and water have important implications for ecosystem functioning and sustainable forest management. However, this is rarely investigated at the large watershed scale with cumulative forest disturbance. We used a combination of techniques including modeling, statistical analysis, and machine learning to investigate the effects of cumulative forest disturbance on water use efficiency (WUE, a proxy for carbon and water coupling) in the 19,200 km2Chilcotin watershed situated in the central interior of British Columbia, Canada. Harvesting, wildfire, and a severe Mountain Pine Beetle (MPB) infestation have gradually cumulated over the 45-year study period, and the watershed reached a cumulative equivalent clear-cut area of 10% in 1999 and then 40% in 2016.

Results

Surprisingly, with the dramatic forest disturbance increase from 2000 to 2016 which was mainly due to MPB, watershed-level carbon stocks and sequestration showed an insignificant reduction. This resilience was mainly due to landscape-level carbon dynamics that saw a balance between a variety of disturbance rates and types, an accumulation of older stand types, and fast growing young regenerated forests. Watershed-level carbon sequestration capacity was sustained, measured by Net Primary Production (NPP). A concurrent significant decrease in annual evapotranspiration (ET), led to a 19% increase in WUE (defined as the ratio of NPP to ET), which is contrary to common findings after disturbance at the forest stand-level. During this period of high disturbance, ET was the dominant driver of the WUE increase.

Conclusions

We conclude that disturbance-driven forest dynamics and the appropriate scale must be considered when investigating carbon and water relationship. In contrast to the stand-level trade-off relationship between carbon and water, forested watersheds may be managed to maintain timber, carbon and water resources across large landscapes.
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

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

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

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

Single-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

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

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

Background

The 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.

Methods

The 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.

Discussion

To 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 registration

ClinicalTrials.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

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

Background

The 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.

Methods

Three 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.

Results

Forty-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.

Conclusions

This 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 registration

PROSPEROCRD42020141011
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

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

The 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.
Life cycle greenhouse gas emissions of ethanol produced via fermentation of sugars derived from shrub willow (Salix ssp.) hot water extraction in the Northeast United States
Authors: Therasme Obste , Volk Timothy A. , Eisenbies Mark H. , Amidon Thomas E. , Fortier Marie-Odile
Published: March 2021

Background

The amount of carbon dioxide in the atmosphere has been on the rise for more than a century. Bioenergy crops are seen by the Intergovernmental Panel on Climate Change as an essential part of the solution to addressing climate change. To understand the potential impact of shrub willow (Salix spp.) crop in the northeast United States, effective and transparent life cycle assessment of these systems needs to occur.

Results

Here we show, ethanol produced from the fermentation of sugars from hot water extract of willow grown on cropland can sequester 0.012 ± 0.003 kg CO2eq MJ−1 for a supply system incorporating summer harvest and storage. Despite decreases in soil organic carbon when willow is instead grown on grassland, the produced fuel still can provide significant climate benefits compared to gasoline.

Conclusions

Shrub willow converted to ethanol can be a carbon negative source of transportation fuel when the electricity and heat required for the conversion process are generated from renewable biomass. The sequestration of carbon in the belowground portion of the plants is essential for the negative GHG balance for cropland and low GHG emissions in grassland.
Time-resolved transcriptional profiling of Trichinella-infected murine myocytes helps to elucidate host–pathogen interactions in the muscle stage
Authors: Hu Xiaoxiang , Liu Xiaolei , Li Chen , Zhang Yulu , Li Chengyao , Li Yanfeng , Chen Yingxi , Guo Heng , Bai Xue , Liu Mingyuan
Published: March 2021

Background

Parasites of the genus Trichinella are the pathogenic agents of trichinellosis, which is a widespread and severe foodborne parasitic disease. Trichinella spiralis resides primarily in mammalian skeletal muscle cells. After invading the cells of the host organism, T. spiralis must elude or invalidate the host’s innate and adaptive immune responses to survive. It is necessary to characterize the pathogenesis of trichinellosis to help to prevent the occurrence and further progression of this disease. The aims of this study were to elucidate the mechanisms of nurse cell formation, pathogenesis and immune evasion of T. spiralis, to provide valuable information for further research investigating the basic cell biology of Trichinella-infected muscle cells and the interaction between T. spiralis and its host.

Methods

We performed transcriptome profiling by RNA sequencing to identify global changes at 1, 3, 7, 10 and 15 days post-infection (dpi) in gene expression in the diaphragm after the parasite entered and persisted within the murine myocytes; the mice were infected by intravenous injection of newborn larvae. Gene expression analysis was based on the alignment results. Differentially expressed genes (DEGs) were identified based on their expression levels in various samples, and functional annotation and enrichment analysis were performed.

Results

The most extensive and dynamic gene expression responses in host diaphragms were observed during early infection (1 dpi). The number of DEGs and genes annotated in the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases decreased significantly in the infected mice compared to the uninfected mice at 3 and 7 dpi, suddenly increased sharply at 10 dpi, and then decreased to a lower level at 15 dpi, similar to that observed at 3 and 7 dpi. The massive initial reaction of the murine muscle cells to Trichinella infection steadied in the later stages of infection, with little additional changes detected for the remaining duration of the studied process. Although there were hundreds of DEGs at each time point, only 11 genes were consistently up- or downregulated at all 5 time points.

Conclusions

The gene expression patterns identified in this study can be employed to characterize the coordinated response of T. spiralis-infected myocytes in a time-resolved manner. This comprehensive dataset presents a distinct and sensitive picture of the interaction between host and parasite during intracellular infection, which can help to elucidate how pathogens evade host defenses and coordinate the biological functions of host cells to survive in the mammalian environment.

Graphical Abstract
Genetic diversity analysis of Dermacentor nuttalli within Inner Mongolia, China
Authors: Gui Zheng , Wu Lin , Cai Hao , Mu Lan , Yu Jing-Feng , Fu Shao-Yin , Si Xiao-Yan
Published: March 2021

Background

Ticks (Arthropoda, Ixodida), after mosquitoes, are the second most prevalent vector of infectious diseases. They are responsible for spreading a multitude of pathogens and threatening the health and welfare of animals and human beings. However, given the history of tick-borne pathogen infections in the Inner Mongolia Autonomous Region of China, surprisingly, neither the genetic diversity nor the spatial distribution of haplotypes within ticks has been studied.

Methods

We characterized the haplotype distribution ofDermacentor nuttalliin four main pastoral areas of the Inner Mongolia Autonomous Region, by sampling 109 individuals (recovered from sheep) in April–August 2019. The 16S rRNA gene, cytochrome c oxidase subunit I (COI), and the internal transcribed spacer 2 region (ITS2) were amplified and sequenced from extracted DNA.

Results

Twenty-six haplotypes were identified using 16S rRNA sequences, 57 haplotypes were identified with COI sequences, and 75 haplotypes were identified with ITS2 sequences. Among the three genes, total haplotype diversity was greater than 0.7, while total nucleotide diversity was greater than 0.06. Neutrality tests revealed a significantly negative Tajima’s D result, while Fu's Fs was not significantly positive. Fixation index values (FST) indicated that the degree of genetic differentiation among some sampled populations was small, while for others it was moderate. Analysis of molecular variance (AMOVA) revealed that the variation within populations was greater than that among populations. The mismatch analysis ofD. nuttalliexhibited double peaks.

Conclusion

The genetic diversity ofD. nuttallipopulations in our region can likely adapt to different geographical environments, thereby leading to genetic diversity, and creating genetic differentiation among different populations. However, genetic differentiation is cryptic and does not form a pedigree geographical structure.

Graphical Abstract
The reproducibility of measuring maximum abdominal aortic aneurysm diameter from ultrasound images
Authors: Matthews Evan O. , Pinchbeck Jenna , Elmore Kylie , Jones Rhondda E. , Moxon Joseph V. , Golledge Jonathan
Published: March 2021

Background

Accurate repeat assessment of the diameter of an abdominal aortic aneurysm (AAA) is important. This study investigated the reproducibility of different methods of measuring AAA diameter from ultrasound images.

Methods

Fifty AAA patients were assessed by ultrasound. Maximum AAA diameter was measured independently by three trained observers on two separate occasions using a standardised protocol. Five diameters were measured from each scan, three in the anterior–posterior (AP) and two in the transverse (TV) plane, including inner-to-inner (ITI), outer-to-outer (OTO) and leading edge-to-leading edge (LETLE). Intra- and inter-observer reproducibility were reported as reproducibility coefficients. Statistical comparison of methods was performed using linear mixed effects models.

Results

Intra-observer reproducibility coefficients (AP LETLE 2.2 mm; AP ITI 2.4 mm; AP OTO 2.6 mm) were smaller than inter-observer reproducibility coefficients (AP LETLE 4.6 mm: AP ITI 4.5; and AP OTO 4.8 mm). There was no statistically significant difference in intra-observer reproducibility of three types of measurements performed in the AP plane. Measurements obtained in the TV plane had statistically significant worse intra-observer reproducibility than those performed in the AP plane.

Conclusions

This study suggests that the comparison of maximum AAA diameter between repeat images is most reproducibly performed by a single trained observer measuring diameters in the AP plane.
Diagnostic accuracy of lung ultrasound for SARS-CoV-2: a retrospective cohort study
Authors: Brenner Daniel S. , Liu Gigi Y. , Omron Rodney , Tang Olive , Garibaldi Brian T. , Fong Tiffany C.
Published: March 2021

Background

As medical infrastructures are strained by SARS-CoV-2, rapid and accurate screening tools are essential. In portions of the world, reverse transcription polymerase chain reaction (RT-PCR) testing remains slow and in limited supply, and computed tomography is expensive, inefficient, and involves exposure to ionizing radiation. Multiple studies evaluating the efficiency of lung point-of-care ultrasound (POCUS) have been published recently, but include relatively small cohorts and often focus on characteristics associated with severe illness rather than screening efficacy. This study utilizes a retrospective cohort to evaluate the test characteristics (sensitivity, specificity, likelihood ratios, predictive values) of lung POCUS in the diagnosis of SARS-CoV-2, and to determine lung score cutoffs that maximize performance for use as a screening tool.

Results

Lung POCUS examinations had sensitivity 86%, specificity 71.6%, NPV 81.7%, and PPV 77.7%. The Lung Ultrasound Score had an area under the curve of 0.84 (95% CI 0.78, 0.90). When including only complete examinations visualizing 12 lung fields, lung POCUS had sensitivity 90.9% and specificity 75.6%, with NPV 87.2% and PPV 82.0% and an area under the curve of 0.89 (95% CI 0.83, 0.96). Lung POCUS was less accurate in patients with a history of interstitial lung disease, severe emphysema, and heart failure.

Conclusions

When applied in the appropriate patient population, lung POCUS is an inexpensive and reliable tool for rapid screening and diagnosis of SARS-CoV-2 in symptomatic patients with influenza-like illness. Adoption of lung POCUS screening for SARS-CoV-2 may identify patients who do not require additional testing and reduce the need for RT-PCR testing in resource-limited environments and during surge periods.
A COVID-19 pregnant patient with thrombotic thrombocytopenic purpura: a case report
Authors: Aminimoghaddam Soheila , Afrooz Narjes , Nasiri Setare , Motaghi Nejad Ozra , Mahmoudzadeh Fatemeh
Published: March 2021

Background

Pregnancy seems to increase the risk of thrombotic thrombocytopenic purpura (TTP) relapses and make the TTP more severe in any of the pregnancy trimesters, or even during the postpartum period.

Case presentation

This study highlights details of treating a COVID-19 pregnant patient who survived. This 21-year addicted White woman was admitted at her 29th week and delivered a stillbirth. She was transferred to another hospital after showing signs of TTP, which was caused by a viral infection.

Conclusion

This viral infection caused fever and dyspnea, and the patient was tested positive for COVID-19 infection. A chest computed tomography scan showed diffuse multiple bilateral consolidations and interlobar septal thickening. She stayed at the Intensive Care Unit for 20 days and treated with plasmapheresis. As far as we know, this is the first report of a TTP pregnant patient with COVID-19 infection.
Hemophagocytic lymphohistiocytosis and myelodysplastic syndrome: a case report and review of the literature
Authors: Sun Y. , Blieden C. , Merritt B. Y. , Sosa R. , Rivero Gustavo
Published: March 2021

Background

Hemophagocytic lymphohistiocytosis (HLH) is characterized by hyperinflammation and life-threatening cytopenias. Survival is poor, and management is pivotal on rapid identification of the disease. HLH is associated with hematologic malignancies, however correlation with myelodysplastic syndromes (MDS) is exceedingly unusual. Although minimizing overwhelming hyperinflammation by treating hemophagocytosis are central for HLH outcome, there is urgent necessity to identify potential initiating mechanisms that could assist in therapy design.

Case description

Here, we describe an elderly African American patient who developed rapid onset of cytopenias and coagulopathy associated with hepatic and bone marrow hemophagocytosis. We analyze four additional similar cases to isolate clinical, laboratory and cytogenetic findings expected in patients exhibiting concurrent HLH and MDS. HLH linked with MDS retains common HLH features associated with systemic hyperinflammation such as fever, hypotension, hepatosplenomegaly, hyperferritinemia, coagulopathy and rapidly evolving cytopenias. Typical MDS chromosomic abnormality such as trisomy 8 was frequently observed in our studied cases.

Conclusion

Our case describes difficulties while managing HLH in MDS patients. Diagnosis should be based on identifying HLH appropriate criteria and if possible karyotypic abnormalities normally observed in MDS.