bluuebunny/crossref_metadata_2025 huggingface dataset:
A model six-month workshop for developing systematic review protocols at teaching hospitals: action research and scholarly productivity
Authors: Tsujimoto Hiraku , Kataoka Yuki , Sato Yukihito , Banno Masahiro , Tsujino-Tsujimoto Emi , Sumi Yukiyoshi , Sada Ryuichi , Fujiwara Takashi , Ohtake Yoichi , Kumasawa Junji , Imura Haruki , Matsuda Yoshinobu , So Ryuhei , Kagawa Tomoko , Yoshioka Takashi , Uneno Yu , Nagano Hiroyuki , Akazawa Mai , Hozumi Takunori , Tsujimoto Yasushi
Published: February 2021

Background

Research engagement contributes to the improvement of patient care. A systematic review is a suitable first scholarly activity because it entails summarization of publicly available data and usually requires neither rigorous ethical review nor research funding.

Methods

This study aimed to develop a model workshop for healthcare staff to acquire skills in creating systematic review protocols based on their own clinical questions at teaching hospitals. We used an action research method to create a model workshop at four hospitals in Japan from April 2015 to March 2017. To improve the program, we solicited reflections using participant questionnaires for each lecture and examined the quality of homework submitted by participants after each lecture. We administered a revised final version of the workshop at five hospitals from April 2016 to March 2017. We evaluated the participants’ scholarly productivity related to these workshops. The observation period was a minimum of 2 years following the workshops.

Results

Most participants had never developed a formal clinical research protocol and voluntarily participated in the workshop. The action research was developed and implemented at nine teaching hospitals in Japan, including one university hospital. The study developed a model nine-step workshop curriculum: 1) Research question development, 2) Search strategy development, 3) Search strategy brush-up, 4) Exclusion and inclusion criteria development, 5) Risk of bias assessment planning, 6) Meta-analysis planning, 7) Subgroup and sensitivity analysis planning, 8) Planning the presentation of results, and 9) Presentation protocols. A total of 233 participants, including medical doctors and other health professionals, produced 414 research questions. Seventy-nine participants (34%) completed the workshop, and 47 review teams accomplished systematic review protocols. The participants published 13 peer-reviewed articles as a result of the workshop.

Conclusions

We developed a structured scholarly productive model workshop for healthcare staff working at hospitals. We found healthcare staff with clinical subspecialties were able to develop an unexpectedly high number of research questions through this workshop. Medical teachers at hospitals with prior systematic review experience could teach how to develop systematic review protocols using this model. Further research is needed to increase the academic productivity of such workshops.

Trial registration

UMIN (https://www.umin.ac.jp/ctr/), UMIN000017107 (4/15/2015), UMIN000025580 (1/10/2017).
Performance evaluation of case definitions of type 1 diabetes for health insurance claims data in Japan
Authors: Okui Tasuku , Nojiri Chinatsu , Kimura Shinichiro , Abe Kentaro , Maeno Sayaka , Minami Masae , Maeda Yasutaka , Tajima Naoko , Kawamura Tomoyuki , Nakashima Naoki
Published: February 2021

Background

No case definition of Type 1 diabetes (T1D) for the claims data has been proposed in Japan yet. This study aimed to evaluate the performance of candidate case definitions for T1D using Electronic health care records (EHR) and claims data in a University Hospital in Japan.

Methods

The EHR and claims data for all the visiting patients in a University Hospital were used. As the candidate case definitions for claims data, we constructed 11 definitions by combinations of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. (ICD 10) code of T1D, the claims code of insulin needles for T1D patients, basal insulin, and syringe pump for continuous subcutaneous insulin infusion (CSII). We constructed a predictive model for T1D patients using disease names, medical practices, and medications as explanatory variables. The predictive model was applied to patients of test group (validation data), and performances of candidate case definitions were evaluated.

Results

As a result of performance evaluation, the sensitivity of the confirmed disease name of T1D was 32.9 (95% CI: 28.4, 37.2), and positive predictive value (PPV) was 33.3 (95% CI: 38.0, 38.4). By using the case definition of both the confirmed diagnosis of T1D and either of the claims code of the two insulin treatment methods (i.e., syringe pump for CSII and insulin needles), PPV improved to 90.2 (95% CI: 85.2, 94.4).

Conclusions

We have established a case definition with high PPV, and the case definition can be used for precisely detecting T1D patients from claims data in Japan.
The CRK2-CYC13 complex functions as an S-phase cyclin-dependent kinase to promote DNA replication in Trypanosoma brucei
Authors: Lee Kyu Joon , Li Ziyin
Published: February 2021

Background

Faithful DNA replication is essential to maintain genomic stability in all living organisms, and the regulatory pathway for DNA replication initiation is conserved from yeast to humans. The evolutionarily ancient human parasiteTrypanosoma brucei, however, lacks many of the conserved DNA replication factors and may employ unusual mechanisms for DNA replication. Neither the S-phase cyclin-dependent kinase (CDK) nor the regulatory pathway governing DNA replication has been previously identified inT. brucei.

Results

Here we report that CRK2 (Cdc2-related kinase 2) complexes with CYC13 (Cyclin13) and functions as an S-phase CDK to promote DNA replication inT. brucei. We further show that CRK2 phosphorylates Mcm3, a subunit of the Mcm2–7 sub-complex of the Cdc45-Mcm2–7-GINS complex, and demonstrate that Mcm3 phosphorylation by CRK2 facilitates interaction with Sld5, a subunit of the GINS sub-complex of the Cdc45-Mcm2–7-GINS complex.

Conclusions

These results identify the CRK2-CYC13 complex as an S-phase regulator inT. bruceiand reveal its role in regulating DNA replication through promoting the assembly of the Cdc45-Mcm2–7-GINS complex.
Cardiovascular surrogate markers and cardiometabolic therapeutics: a viewpoint learned from clinical trials on dipeptidyl peptidase-4 inhibitors
Authors: Tanaka Atsushi , Node Koichi
Published: February 2021

Clinical trials are often performed to investigate the effects of various types of cardiometabolic therapies on cardiovascular surrogate markers, including vascular function and biomarkers. This study platform has the potential to provide information on the suspected actions of drugs and mechanistic insights into their prognostic impact. However, despite using the same class of drugs and similar study designs we are often faced with inconsistent and even conflicting results, possibly leading to some confusion in the clinical setting. When interpreting these results, it is important to investigate what caused the differences and carefully assess the information, taking into account the research situation and the patient population investigated. Using this approach, assessment of the impact on cardiovascular surrogate markers observed in clinical studies from multiple perspectives should help to better understand the potential cardiovascular effects. In this commentary we discuss how we should interpret the effects of cardiometabolic therapeutics on vascular surrogate markers, based on viewpoints learned from the results of clinical trials on dipeptidyl peptidase-4 inhibitors. This learning strategy could also be helpful for appropriate selection of drugs for evidence-based, patient-centric, tailored medication.
SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system
Authors: Bonora Benedetta Maria , Raschi Emanuel , Avogaro Angelo , Fadini Gian Paolo
Published: February 2021

Background

Sodium glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of heart failure and new data show they can prevent atrial fibrillation (AF). We examined the association between SGLT2i and AF in the Food and Drug Administration adverse event reporting system (FAERS).

Methods

We mined the FAERS from 2014q1 to 2019q4 to compare AF reporting for SGLT-2 i versus reports for other glucose lowering medications (ATC10 class). Several exclusions were sequentially applied for: concomitant medications; diabetes, cardiovascular or renal disease indication; reports for competing adverse events (genitourinary tract infections, ketoacidosis, Fournier’s gangrene, amputation). We provide descriptive statistics and calculated proportional reporting ratios (PRR).

Results

There were 62,098 adverse event reports for SGLT2i and 642,031 reports for other ATC10 drugs. The reporting of AF was significantly lower with SGLT2i than with other ATC10 drugs (4.8 versus 8.7/1000; p < 0.001) with a PRR of 0.55 (0.49–0.62). Results did not change substantially after excluding reports listing insulin (PRR 0.49) or anti-arrhythmics (PRR 0.59) as suspect or concomitant drugs, excluding reports with indications for cardiovascular disease (PRR 0.49) or renal disease (PRR 0.55), and those filed for competing adverse events (PRR 0.63). Results were always statistically significant whether the diabetes indication was specified. Negative and positive controls confirmed internal validity of the database.

Conclusions

In a large pharmacovigilance database, AF was robustly and consistently reported more frequently for diabetes medications other than SGLT2i. This finding complements available evidence from trials supporting a protective role of SGLT2i against the occurrence of AF.
Exposure to traffic-related air pollution and changes in exhaled nitric oxide and DNA methylation in arginase and nitric oxide synthase in children with asthma
Authors: Ji N. , Fang M. , Baptista A. , Cepeda C. , Greenberg M. , Mincey I. Colon , Ohman-Strickland P. , Haynes F. , Fiedler N. , Kipen H. M. , Laumbach R. J.
Published: February 2021

Background

Traffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma.

Methods

We measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level.

Results

Exposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0–6 h while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13–24 h and lag 0–24 h, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed.

Conclusions

Exposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.
The association of parameters of body composition and laboratory markers with the severity of hypertriglyceridemia-induced pancreatitis
Authors: Chen Lifang , Huang Yingbao , Yu Huajun , Pan Kehua , Zhang Zhao , Man Yi , Hu Dingyuan
Published: February 2021

Background

Hypertriglyceridemia has arisen as the third leading cause of acute pancreatitis. This study aimed at exploring the association between the severity of hypertriglyceridemia-induced pancreatitis (HTGP) and computed tomography (CT)-based body composition parameters and laboratory markers.

Methods

Laboratory and clinical parameters were collected from 242 patients with HTGP between 2017 and 2020. Severity of HTGP was evaluated by original or modified CT severity index. Body composition parameters such as area and radiodensity of muscle, subcutaneous adipose tissue and visceral adipose tissue were calculated by CT at the level of third lumbar vertebra. Parameters were compared between mild and moderately severe to severe HTGP. Uni-variate and multi-variate Logistic regression analyses were employed to assess the risk factors of the severity of HTGP.

Results

Seventy patients (28.9%) presented with mild HTGP. Body mass index, waist circumference and all CT-based body composition parameters differed between male and female patients. None was associated with the severity of HTGP, neither in males nor in females. Receiver operating characteristic curves showed that areas under the curves of apolipoprotein A-I and albumin to predict the severity of HTGP were 0.786 and 0.759, respectively (allP < 0.001). Uni-variate and further multi-variate Logistic regression analysis confirmed that low serum albumin (< 35 g/L,P = 0.004, OR = 3.362, 95%CI = 1.492–8.823) and apolipoprotein A-I (< 1.1 g/L,P < 0.001, OR = 5.126, 95%CI = 2.348–11.195), as well as high C-reactive protein (> 90 mg/L,P = 0.005, OR = 3.061, 95%CI = 1.407–6.659) and lipase (P = 0.033, OR = 2.283, 95%CI = 1.070–4.873) were risk factors of moderately severe to severe HTGP. Levels of albumin, apolipoprotein A-I, C-reactive protein and lipase were also associated with the length of hospital stay (allP < 0.05). Besides, low serum albumin, low-density lipoprotein cholesterol and high radiodensity of subcutaneous adipose tissue were significant risk factors of pancreatic necrosis in patients with HTGP (allP < 0.05).

Conclusions

Low serum albumin and apolipoprotein A-I, and high C-reactive protein and lipase upon admission were associated with a more severe type of HTGP and longer hospital stay for these patients. Albumin and apolipoprotein A-I may serve as novel biomarkers for the severity of HTGP. However, none of the body composition parameters was associated with the severity of HTGP.
The impact of thrombocytopenia on prognosis of HBV-related small hepatocellular carcinoma: a propensity score matching analysis
Authors: Peng Wei , Li Chuan , Zhang Xiaoyun , Wen Tianfu , Chen Zheyu
Published: February 2021

Background

Thrombocytopenia was reported both detrimental and advantageous to hepatocellular carcinoma (HCC). However, there is little evidence showing clearly the clinical value of preoperative thrombocytopenia on the surgical outcome of patients with small HCC. This retrospective study aimed at elucidating the correlation between preoperative thrombocytopenia and surgical outcome of small HCC patients within Milan criteria treated with liver resection.

Methods

Data of hepatitis B virus (HBV)-related small HCC patients were retrospectively analyzed, and we performed the propensity score matching (PSM) analysis to overcome the imbalance of clinicopathological features. Patients enrolled were subsequently categorized into two groups according to preoperative platelet counts: thrombocytopenia group and non-thrombocytopenia group. Survival outcomes of the patients in both groups were described with the Kaplan-Meier method, and the difference was compared with a log-rank test. Cox regression analysis was applied to identify the risk factors of surgical outcome.

Results

After PSM, the estimated 1-, 3-, and 5-year overall survival (OS) rates for small HCC patients in the thrombocytopenia group were 94.5%, 77.0%, and 57.6%, and 95.0%, 79.6%, and 68.0%, respectively, for small HCC patients in the non-thrombocytopenia group (P= 0.042). And the 1-, 3-, and 5-year estimated recurrence-free survival (RFS) rates for small HCC patients in the thrombocytopenia group were 70.4%, 51.0%, and 42.1%, and 83.8%, 63.7%, and 46.7%, respectively, for small HCC patients in the non-thrombocytopenia group (P= 0.035). Multivariate analysis indicated preoperative thrombocytopenia was a significant prognosticator of poor RFS (hazard ratio (HR) = 1.388, 95% confidence interval (CI) 1.028~1.874,P= 0.033).

Conclusion

Preoperative thrombocytopenia had an undesirable impact on the recurrence of small HCC patients treated with liver resection.
Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity
Authors: Gao Yuan , Xu Guang , Ma Li , Shi Wei , Wang Zhilei , Zhan Xiaoyan , Qin Nan , He Tingting , Guo Yuming , Niu Ming , Wang Jiabo , Bai Zhaofang , Xiao Xiaohe
Published: February 2021

Background

Epimedii Folium (EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI.

Methods

Bone-marrow-derived macrophages (BMDMs) were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo.

Results

Icariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mouse model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation.

Conclusions

Our study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI.
PSF functions as a repressor of hypoxia-induced angiogenesis by promoting mitochondrial function
Authors: Dong Lijie , Li Wenbo , Lin Tingting , Liu Boshi , Hong Yaru , Zhang Xiaomin , Li Xiaorong
Published: February 2021

Background

Abnormal neovascularization is the most common cause of blindness, and hypoxia alters tissue metabolism, function, and morphology. HIF-1α, the transcriptional activator of VEGF, has intricate mechanisms of nuclear translocation and activation, but its signal termination mechanisms remain unclear.

Methods

We investigated the role of polypyrimidine tract-binding protein-associated splicing factor (PSF) in cellular energy production, migration, and proliferation by targeting HIF-1α in vivo and in vitro PSF plasmids were transfected with liposome 2000 transfection reagent. Young C57/BL6J mice were kept in a hyperoxia environment, followed by indoor air, resulting in oxygen-induced retinopathy. Oxygen-induced retinopathy (OIR) animals were randomly divided into three groups: OIR group, OIR + vector group (OIR cubs treated with rAAV vector) and OIR + PSF group (OIR cubs treated with rAAV-PSF). Age-matched C57/BL6J mice were used as controls and exposed to constant normoxic conditions. The animals were executed and their pupils were subjected to subsequent experiments. The metabolic spectrum was analyzed by Seahorse XFe96 flux analyzer, and OCR and extracellular acidification rate were quantified at the same time.

Results

PSF ameliorated retinal neovascularization and corrected abnormal VEGF expression in mice with oxygen-induced retinopathy and reduced intra-retinal neovascularization in Vldlr − / − mice. PSF reprogrammed mitochondrial bioenergetics and inhibited the transition of endothelial cells after hypoxia, suggesting its involvement in pathological angiogenesis.Ectopic PSF expression inhibited hypoxia-induced HIF-1α activation in the nucleus by recruiting Hakai to the PSF/HIF-1α complex, causing HIF-1α inhibition. PSF knockdown increased hypoxia-stimulated HIF-1α reactions. These hypoxia-dependent processes may play a vital role in cell metabolism, migration, and proliferation. Thus, PSF is a potential treatment target in neovascularization-associated ophthalmopathy.

Conclusion

This is the first study showing that PSF inhibits HIF-1α via recruitment of Hakai, modulates mitochondrial oxidation and glycolysis, and downregulates VEGF expression under hypoxia. We propose a new HIF-1 α/Hakai regulatory mechanism that may play a vital role in the pathogenesis of neovascularization in ophthalmopathy.

PSF-Hakai–HIF-1α signaling pathway under hypoxia condition. Schematic diagram showing that the PSF-Hakai–HIF-1α signaling pathway. Under hypoxia condition, PSF-Hakai complex regulate HIF-1α signaling, thus inhibiting downstream target gene VEGF, cell metabolism and angiogenesis eventually.
Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities
Authors: Zhang Xinxin , Qin Yating , Wan Xiaoning , Liu Hao , Lv Chao , Ruan Weibin , He Lin , Lu Li , Guo Xiaomei
Published: February 2021

Background

Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions.

Methods

All male Apolipoprotein E-deficient (ApoE−/−) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages.

Results

Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE−/− mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively.

Conclusions

Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.
Macrophage activation syndrome in a newborn: report of a case associated with neonatal lupus erythematosus and a summary of the literature
Authors: Heijstek Veerle , Habib Meelad , van der Palen Roel , van Doorn Remco , Muller Petra Hissink
Published: February 2021

Background

Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome and is caused by a severely dysregulated immune response. It has rarely been associated with neonatal lupus.

Case presentation

We present a female neonate with MAS born to a mother who had cutaneous lupus erythematosus with circulating anti-nuclear antibodies (ANA), anti-SSA, anti-SSB and anti-extractable nuclear antigen (anti-ENA) antibodies.

Because of neonatal lupus (NLE) with a total atrioventricular block, epicardial pacemaker implantation was required on the sixth day of life. Following surgery she developed non-remitting fever and disseminated erythematous skin lesions. A diagnosis of MAS was made based on these symptoms, with hyperferritinemia, elevated transaminases, hypertriglyceridemia, and a skin biopsy that showed hemophagocytosis. Our patient was treated with steroids for 3 months with good effect. No relapse has occurred.

Conclusions

MAS is a rare complication of neonatal lupus that may be difficult to diagnose, but needs to be treated promptly. In this article, pathogenesis and overlap of MAS and hemophagocytic lymphohistiocytosis (HLH) has been described.

Diagnosis of MAS can be difficult. Different diagnostic criteria are used in both diagnosing MAS and HLH. Validated criteria for diagnosis of MAS in other disease than systemic onset JIA have not been validated yet. In NLE, diagnosing MAS is even more difficult, since skin lesions are already common in NLE. We show the potential additional value of skin biopsy in diagnosing MAS.
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

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

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

Background

Although 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.

Methods

We 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.

Results

We 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.

Conclusion

Integrated 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

Introduction

Cervical 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.

Methods

We 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.

Results

We 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).

Conclusions

Knowledge 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

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

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

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.
Correction to: FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
Authors: Sun Cheng-Cao , Zhu Wei , Li Shu-Jun , Hu Wei , Zhang Jian , Zhuo Yue , Zhang Han , Wang Juan , Zhang Yu , Huang Shao-Xin , He Qi-Qiang , Li De-Jia
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
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

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

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.