bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immersive virtual reality health games: a narrative review of game design
Authors: Tao Gordon , Garrett Bernie , Taverner Tarnia , Cordingley Elliott , Sun Crystal 
Published: February 2021

Abstract
Background
High quality head-mounted display based virtual reality (HMD-VR) has become widely available, spurring greater development of HMD-VR health games. As a behavior change approach, these applications use HMD-VR and game-based formats to support long-term engagement with therapeutic interventions. While the bulk of research to date has primarily focused on the therapeutic efficacy of particular HMD-VR health games, how developers and researchers incorporate best-practices in game design to achieve engaging experiences remains underexplored. This paper presents the findings of a narrative review exploring the trends and future directions of game design for HMD-VR health games.

Methods
We searched the literature on the intersection between HMD-VR, games, and health in databases including MEDLINE, Embase, CINAHL, PsycINFO, and Compendex. We identified articles describing HMD-VR games designed specifically as health applications from 2015 onwards in English. HMD-VR health games were charted and tabulated according to technology, health context, outcomes, and user engagement in game design.

Findings
We identified 29 HMD-VR health games from 2015 to 2020, with the majority addressing health contexts related to physical exercise, motor rehabilitation, and pain. These games typically involved obstacle-based challenges and extrinsic reward systems to engage clients in interventions related to physical functioning and pain. Less common were games emphasizing narrative experiences and non-physical exercise interventions. However, discourse regarding game design was diverse and often lacked sufficient detail. Game experience was evaluated using primarily ad-hoc questionnaires. User engagement in the development of HMD-VR health games primarily manifested as user studies.

Conclusion
HMD-VR health games are promising tools for engaging clients in highly immersive experiences designed to address diverse health contexts. However, more in-depth and structured attention to how HMD-VR health games are designed as game experiences is needed. Future development of HMD-VR health games may also benefit from greater involvement of end-users in participatory approaches.
A micro costing analysis of the development of a primary care intervention to improve the uptake of diabetic retinopathy screening
Authors: Ahern Susan , Riordan Fiona , Murphy Aileen , Browne John , Kearney Patricia M. , Smith Susan M. , McHugh Sheena M. 
Published: February 2021

Abstract
Background
The application of economic analysis within implementation science is still developing and the cost of intervention development, which differs markedly from the costs of initial implementation and maintenance, is often overlooked. Our aim was to retrospectively cost the development of a multifaceted intervention in primary care to improve attendance at diabetic retinopathy screening.

Methods
A retrospective micro costing of developing the intervention from the research funder perspective was conducted. It was based on a systematic intervention development process involving analysis of existing audit data and interviews with patients and healthcare professionals (HCPs), conducting consensus meetings with patients and HCPs, and using these data together with a rapid review of the effectiveness of interventions, to inform the final intervention. Both direct (non-personnel, e.g. travel, stationary, room hire) and indirect (personnel) costs were included. Data sources included researcher time logs, payroll data, salary scales, an online financial management system, invoices and purchase orders. Personnel involved in the intervention development were consulted to determine the activities they conducted and the duration of their involvement. Sensitivity and scenario analyses were conducted to estimate uncertainty around parameters and scope.

Results
The total cost of intervention development (July 2014–January 2019) was €40,485 of which 78% were indirect (personnel) costs (€31,451). In total, personnel contributed 1368 h to intervention development. Highest cost activities were the patient interviews, and consensus process, contributing 23% and 34% of the total cost. Varying estimated time spent on intervention development activities by + 10% increased total intervention development cost by 6% to €42,982.

Conclusions
Our results highlight that intervention development requires a significant amount of human capital input, combining research experience, patient and public experience, and expert knowledge in relevant fields. The time committed to intervention development is critical but has a significant opportunity cost. With limited resources for research on developing and implementing interventions, capturing intervention development costs and incorporating them as part of assessment of cost-effective interventions, could inform research priority and resource allocation decisions.
Integrated traditional Chinese medicine alleviates sciatica while regulating gene expression in peripheral blood
Authors: Wang Yi , Dai Guogang , Xu Yan , Jiang Ling , Fu Zhibin , Xia Jiao , Tian Guogang , Du Wanli 
Published: February 2021

AbstractBackgroundAlthough integrated traditional Chinese medicine (TCM) has long been indicated to be effective in the treatment of sciatica and is widely used in the management of this condition, the mechanism by which integrated TCM alleviates sciatica has not yet been fully defined, and the effect of integrated TCM on gene expression in the peripheral blood of patients with sciatica is still unknown. We performed this study to investigate the effect of integrated TCM on peripheral blood gene expression in patients with sciatica and to explore new clues for studying the mechanism of integrated TCM in alleviating sciatica.MethodsWe used a microarray to identify differentially expressed genes (DEGs) in the peripheral blood of patients with sciatica and healthy controls (DEGs-baseline), bioinformatic analysis to reveal the characteristics of DEGs-baseline, and the key genes that contribute to the gene dysregulation. A microarray was also used to identify DEGs in the peripheral blood of patients with sciatica after integrated TCM treatment compared with those at baseline, and the expression levels of DEGs were validated by qRT-PCR.ResultsWe identified 153 DEGs-baseline, which included 131 upregulated genes and 22 downregulated genes. Bioinformatic analysis revealed that most of the DEGs-baseline were related to immunity and the inflammatory response and that TLR4, MMP9, MPO, CAMP, RETN, TLR5, and IL1RN were key genes involved in the dysregulation of genes in the peripheral blood of patients with sciatica. The expression levels of TLR5, IL1RN, SLC8A1, RBM20, GPER1, IL27, SOCS1, and GRTP1-AS1 were decreased in the peripheral blood of patients after integrated TCM treatment compared with that at baseline, which was accompanied by relief of pain.ConclusionIntegrated TCM treatment relieved pain while regulating the gene expression of TLR5, IL1RN, SLC8A1, RBM20, GPER1, IL27, SOCS1, and GRTP1-AS1 in the peripheral blood of patients with sciatica. Our study provides new clues for studying the mechanism of TCM in treating sciatica.
Low level of knowledge about cervical cancer among Ethiopian women: a systematic review and meta-analysis
Authors: Derbie Awoke , Mekonnen Daniel , Misgan Eyaya , Alemu Yihun Mulugeta , Woldeamanuel Yimtubezinash , Abebe Tamrat 
Published: February 2021

AbstractIntroductionCervical cancer is one of the leading causes of malignancies among women in Ethiopia. Knowing the disease could empower women to make an informed decision regarding participation with cervical cancer prevention strategies. There is scarcity of compiled data in the field. Therefore, this systematic review aimed to provide an overview of knowledge about cervical cancer among Ethiopian women.MethodsWe conducted a systematic review of peer-reviewed articles on the knowledge of cervical cancer. Articles were systematically searched using comprehensive search strings from PubMed/Medline, SCOPUS, and grey literature from Google Scholar. Two reviewers assessed study eligibility, extracted data, and the risk of bias independently. Meta-analysis was performed using STATA v 14 to pool the overall knowledge of the women about cervical cancer.ResultsWe included 26 articles published between 2013 and 2020 covering a total of 14,549 participants. All the included articles had good methodological quality. The proportion of participants who had heard of cervical cancer varied from 4.6 to 87.7% with the pooled estimate at 56% (95% CI: 47–66). Similarly, the proportion of participants who knew that HPV is the main cause of cervical cancer lied between 0 and 49.7% with the pooled result at 21% (95% CI: 13–30). Likewise, the pooled prevalence to identify at least one risk factor, one symptom of cervical cancer and ever heard of cervical cancer screening was gauged at 52% (95% CI: 39–64), 43% (95% CI: 26–60), and 39% (95% CI: 24–55), respectively. The overall pooled prevalence of good knowledge about cervical cancer was at 43% (95% CI: 33–53). On top of this, the prevalence of previous screening practice among the participants was at 14% (95% CI: 9–20).ConclusionsKnowledge about cervical cancer among Ethiopian women is quite poor. Therefore, health education to provide sufficient and unbiased information about HPV and cervical cancer in general is required to the public.
Parent- and teacher-reported long-term effects of parent training on child conduct problems in families with child protection and other support services: a randomized controlled trial
Authors: Karjalainen Piia , Santalahti Päivi , Aronen Eeva T. , Kiviruusu Olli 
Published: February 2021

Abstract
Background
This randomized controlled trial (RCT) evaluated the long-term effectiveness of the Incredible Years® (IY) Parenting Program in modifying children’s externalizing problems among families in Child Protection Services (CPS) and using other special support services. We also examined whether parent-reported effects of the IY® generalize to the daycare/school setting as reported by teachers.

Methods
Participants in the study were 3–7-year-old children with behavioural problems (N = 102 at baseline, N = 89 at one-year follow-up). Participants were randomized to intervention (N = 50) and control groups (N = 52) after the baseline assessment. The intervention group received 19-week IY® Parenting Program. The effectiveness of the intervention was analyzed using linear mixed model.

Results
Our previously reported pre-post intervention effects on CBCL (Child Behavior Checklist) and ECBI (Eyberg Child Behavior Inventory) were not sustained to the one-year follow-up. Child conduct problems decreased from baseline to follow-up in both intervention and control groups. The positive changes were not observed at daycare/school from baseline to post-intervention or to the one-year follow-up, and there were no significant differences in changes between the groups.

Conclusions
Evidence-based parenting program IY® seems to be an effective intervention for child conduct problems in the short term in families in the CPS context, but sustaining the positive effects and generalizing them to the daycare/school context are challenging.
Trial registration: The trial is registered in the ClinicalTrials.gov registry (NCT03239990), Registered August 4th, 2017; https://clinicaltrials.gov/ct2/results?cond=&term=NCT03239990&cntry=&state=&city=&dist=
Acceptability and feasibility of a community-based strength, balance, and Tai Chi rehabilitation program in improving physical function and balance of patients after total knee arthroplasty: study protocol for a pilot randomized controlled trial
Authors: Lo Cathy W. T. , Brodie Matthew A. , Tsang William W. N. , Yan Chun-Hoi , Lam Priscillia L. , Chan Chun-Ming , Lord Stephen R. , Wong Arnold Y. L. 
Published: February 2021

Abstract
Background
The rate of falls in patients after total knee arthroplasty (TKA) is high and related to lower limb muscle weakness and poor balance control. However, since routine post-TKA rehabilitation is uncommon, it is paramount to explore alternative strategies to enhance balance and physical functioning in post-TKA patients. As Tai Chi is a proven strategy for improving balance in older people, the proposed study aims to determine the feasibility and acceptability of a 12-week community-based post-TKA multimodal Tai Chi program and to collect preliminary data with respect to the efficacy of such a program in improving balance and physical functioning in post-TKA patients as compared to usual postoperative care.

Methods
A single-blinded 2-arm pilot randomized controlled trial will recruit 52 community-dwelling post-TKA patients (aged > 60 years) in Hong Kong. In addition, 26 untreated asymptomatic controls will be recruited for comparison purposes. The TKA patients will be randomized into either a 12-week multimodal Tai Chi rehabilitation group or a postoperative usual care group (26 each). Participants will perform the outcome assessments at baseline, 6, 12, 24, and 52 weeks after TKA, while asymptomatic controls will have the same assessments at baseline, 12, and 52 weeks after baseline. The rate of recruitment, retention, and attrition, as well as adherence to the intervention, will be measured and used to determine the feasibility of the study and whether a full-scale effectiveness trial is warranted. Further, qualitative interviews will be conducted to explore the acceptability and possible barriers to the implementation of the intervention. Primary and secondary outcomes including both patient-reported surveys and performance-based tests will be compared within and between groups.

Discussion
The study will determine the feasibility and acceptability/potential efficacy of community-based rehabilitation for post-TKA patients and assess whether the intervention has the potential to be assessed in a future fully powered effectiveness trial. The findings will also be used to refine the study design and guide the conduction of a future definitive randomized controlled trial.

Trial registration
ClinicalTrials.gov NCT03615638. Registered on 30 May 2018. https://clinicaltrials.gov/ct2/show/NCT03565380
Mitigation of deleterious phenotypes in chloroplast-engineered plants accumulating high levels of foreign proteins
Authors: Schmidt Jennifer A. , Richter Lubna V. , Condoluci Lisa A. , Ahner Beth A. 
Published: February 2021

Abstract
Background
The global demand for functional proteins is extensive, diverse, and constantly increasing. Medicine, agriculture, and industrial manufacturing all rely on high-quality proteins as major active components or process additives. Historically, these demands have been met by microbial bioreactors that are expensive to operate and maintain, prone to contamination, and relatively inflexible to changing market demands. Well-established crop cultivation techniques coupled with new advancements in genetic engineering may offer a cheaper and more versatile protein production platform. Chloroplast-engineered plants, like tobacco, have the potential to produce large quantities of high-value proteins, but often result in engineered plants with mutant phenotypes. This technology needs to be fine-tuned for commercial applications to maximize target protein yield while maintaining robust plant growth.

Results
Here, we show that a previously developed Nicotiana tabacum line, TetC-cel6A, can produce an industrial cellulase at levels of up to 28% of total soluble protein (TSP) with a slight dwarf phenotype but no loss in biomass. In seedlings, the dwarf phenotype is recovered by exogenous application of gibberellic acid. We also demonstrate that accumulating foreign protein represents an added burden to the plants’ metabolism that can make them more sensitive to limiting growth conditions such as low nitrogen. The biomass of nitrogen-limited TetC-cel6A plants was found to be as much as 40% lower than wildtype (WT) tobacco, although heterologous cellulase production was not greatly reduced compared to well-fertilized TetC-cel6A plants. Furthermore, cultivation at elevated carbon dioxide (1600 ppm CO2) restored biomass accumulation in TetC-cel6A plants to that of WT, while also increasing total heterologous protein yield (mg Cel6A plant−1) by 50–70%.

Conclusions
The work reported here demonstrates that well-fertilized tobacco plants have a substantial degree of flexibility in protein metabolism and can accommodate considerable levels of some recombinant proteins without exhibiting deleterious mutant phenotypes. Furthermore, we show that the alterations to protein expression triggered by growth at elevated CO2 can help rebalance endogenous protein expression and/or increase foreign protein production in chloroplast-engineered tobacco.
A 23-year-old man with acute lung injury after using a tetrahydrocannabinol-containing vaping device: a case report
Authors: Lucero Anthony , Eriksson Niklas , Nichta Carli , Sokol Kimberly 
Published: February 2021

Abstract
Background
Vaping-associated lung injury is a newly emerging disease process with the potential for serious health implications and high mortality, even despite the lack of underlying lung disease. We present a case of a young, otherwise healthy patient with tetrahydrocannabinol vaping-associated lung injury.

Case presentation
A 23-year-old Caucasian man with a past history of tetrahydrocannabinol vaping and benzodiazepine and methamphetamine abuse presented to the emergency department of our institution with a complaint of “feeling malnourished” over the past 5 days, along with associated fevers, cough, and vomiting. His past medical, surgical, family, and social histories were significant only for the recent use of marijuana vaping pens. Upon initial presentation, the patient appeared to be in significant respiratory distress. A computed tomographic scan of his chest demonstrated diffuse central predominant interstitial opacities, and he was admitted to the medical intensive care unit, where he was eventually intubated for hypoxic respiratory failure. No other cause of his respiratory failure was found, and it was ultimately believed that the patient had sustained a vaping-associated lung injury.

Conclusion
Tetrahydrocannabinol-containing vaping-associated lung injury is still poorly understood overall and is currently being investigated by the Centers for Disease Control and Prevention. In the meantime, physicians should consider vaping to be a public health emergency. We summarize the appropriate history, physical examination, appropriate workup, and therapies that physicians should be aware of in order to appropriately manage and treat patients presenting with suspected vaping-associated lung injury.
Transient complete atrioventricular block and ST-segment elevation induced by coronary vasospasm due to iatrogenic hyperkalemia: a case report
Authors: Cao Miaomiao , Chen Li , Sun Chaofeng , Li Guoliang 
Published: February 2021

Abstract
Background
Hyperkalemia and acute coronary syndrome are not only all responsible for syncope related to complete atrioventricular block, but also share parts of electrocardiogram manifestations. Additionally, they influence each other.

Case presentation
A 32-year-old Chinese man presented with severe hypokalemia (1.63 mmol/l) at midnight in the emergency room. He developed unexpected rebound hyperkalemia (7.76 mmol/l) after 18 hours of oral and intravenous potassium chloride supplementation at a concentration of about 10 g/day and a rate of 10 mmol/hour. Subsequently, the patient complained of chest discomfort and dyspnea, followed by syncope for several minutes, approximately 2 hours after potassium reduction treatment had been started. The instant electrocardiogram showed complete atrioventricular block and elevated ST segment in the inferolateral leads, which resolved 15 minutes later, before hyperkalemia was corrected. Combined with mild coronary stenosis and negative myocardial injury markers, transient complete atrioventricular block induced by coronary vasospasm due to iatrogenic hyperkalemia was diagnosed. Normal urine potassium excretion, acid–base state, and other examinations made the diagnosis of hypokalemic periodic paralysis possible.

Conclusions
Hyperkalemia may provoke acute coronary syndrome, and early coronary angiography is an effective strategy for identifying the direct cause of acute complete atrioventricular block.
Poor outcome associated with mucormycosis in critically ill hematological patients: results of a multicenter study
Authors: Jestin Matthieu , Azoulay Elie , Pène Frédéric , Bruneel Fabrice , Mayaux Julien , Murgier Martin , Darmon Michael , Valade Sandrine 
Published: February 2021

AbstractBackgroundMucormycosis is an emerging fungal infection that may lead to multi-organ failure, especially in patients with hematological malignancies (HM). We performed a retrospective, cohort study, in five intensive care units (ICU) to assess the outcome of critically ill patients with HM and mucormycosis between 2002 and 2018. The secondary objective was to identify prognostic factors in this setting.ResultsTwenty-six patients were included with a median age of 38 years [IQR, 26–57]). Acute leukemia was the most frequent underlying disease (50%). Nine patients (35%) underwent allogeneic stem cell transplantation (SCT). Nineteen patients (73%) had neutropenia and 16 (62%) had received steroids. The main reason for admission was acute respiratory failure (n = 14, 54%) followed by shock (n = 5 19%). The median SOFA score at admission was 7 [5–8].According to EORTC/MSG criteria, mucormycosis was "proven" in 14 patients (54%), "probable" in 5 (19%) and “possible” in 7 (27%) in whom diagnosis was made by qPCR.RhizopusandMucorwere the most frequent documented species. Seven patients (27%) had concurrentAspergillusinfection. Mucormycosis was diagnosed 1 day [−4 to + 6] after ICU admission. Sixteen patients (62%) had pulmonary involvement and ten (38%) rhino-cerebral involvement. Infection was disseminated in eight patients (31%). Twenty-two patients (85%) were treated with liposomal amphotericin B; 12 (46%) received antifungal combination including posaconazole in 7. Eight patients (31%) underwent curative surgery. Twenty-one patients (81%) required invasive mechanical ventilation (IMV), 18 (69%) vasopressors, and 9 (35%) renal replacement therapy. ICU and hospital mortality rates were 77% and 88%, respectively. The median overall survival was 9 days [3–22]. IMV was strongly associated with ICU mortality (p < 0.001) Three variables were associated with day 90 mortality in a Cox model including allogeneic SCT (HR 4.84 [95% CI 1.64–14.32]), SOFA score (1.19 [1.02–1.39]) and dual therapy (3.02 [1.18–7.72]).ConclusionsMucormycosis is associated with a high mortality rate in patients with HM, especially in allogeneic SCT recipients. Benefit of ICU management in these patients should be assessed before admission and strategies aiming to improve these patients’ outcome are urgently needed.