bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual inverted classroom to replace in-person radiology lectures at the time of the COVID-19 pandemic - a prospective evaluation and historic comparison
Authors: Teichgräber Ulf , Mensel Birger , Franiel Tobias , Herzog Aimée , Cho-Nöth Chie-Hee , Mentzel Hans-Joachim , Ingwersen Maja , Aschenbach René
Published: December 2021

Background

In the time of the coronavirus disease 2019 (COVID-19) pandemic, in-person lectures had to be shifted to online learning. This study aimed to evaluate students’ and lecturers’ perception and effectiveness of a virtual inverted classroom (VIC) concept on clinical radiology in comparison to a historic control.

Methods

In the winter semester 2020/21, 136 fourth year medical students who completed the clinical radiology VIC during the pandemic, were included in the single centre, prospective study. Results were compared with a historic control that had finished the physical inverted classroom (PIC) in the immediately preceding year. The VIC consisted of an initial phase of self-determined preparation with learning videos and a second interactive phase of clinical case studies alternating between the virtual lecture hall and virtual buzz groups. At the end of the lecture series, students rated the lecture on a scale of 1 (most positive assessment) to 6 (most negative assessment) through an online survey platform. Additionally, they reported their impressions in free-form text. Lecturers were invited to comment on the VIC in a group interview. Main outcomes were final grades and student perception of the VIC.

Results

Students’ general impression of VIC was lower than that of PIC (median value of 3 [IQR 4, 2] and 1 [IQR 0, 0], p < 0.001), respectively, p < 0.001). The highest rating was achieved concerning use of the audience response system (median 1 [IQR 1, 0]), and the lowest concerning the buzz groups (median 4 [IQR 5, 3]). Students stated that they would have appreciated more details on reading images, greater focus on plenary case studies, and provision of exam related scripts. Lecturers would have liked better preparation by students, more activity of students, and stronger assistance for group support. Exam grades after VIC were better than after PIC (median 1 [IQR 2, 1] and 2 [IQR 2,1], respectively, p < 0.001).

Conclusions

Students’ overall perception of VIC was satisfactory, although worse than PIC. Final grades improved compared to PIC. Provided an adapted buzz group size and support, VIC may serve as complement in medical education once the pandemic is over.
The impact of implementing a person-centred pain management intervention on resistance to change and organizational culture
Authors: Angelini Eva , Wolf Axel , Wijk Helle , Brisby Helena , Baranto Adad
Published: December 2021

Background

Resistance to change and organizational culture are essential factors to consider in change management in health care settings. Implementation of structural change remains a challenge. There is a lack of studies providing information on the impact of implementation processes on the organization. The aim of this study was to describe the impact of implementing a systematic change process concerning postoperative person-centred pain management on resistance to change and organizational culture in an orthopaedic spine surgery unit.

Methods

The study was set in an orthopaedic spine surgery unit at a university hospital. Person-centred bundles of care for postoperative pain management of spine surgery patients were developed in co-creation by a multi-professional expert group and implemented throughout the care pathway. The intervention was underpinned by theories on organizational culture and inspired by principles of person-centred care. Quantitative data were collected using the Resistance to Change Scale and the Organizational Culture Assessment Instrument and analysed using descriptive statistics.

Results

The findings showed a low resistance to change decreasing during the study. The organizational culture shifted from a result-oriented to a formalized and structured culture after the implementation. The culture preferred by the staff was team-oriented and participation-focused throughout the study. The discrepancy between the current and preferred cultures remained extensive over time.

Conclusion

It is challenging to describe the influence of the development and implementation of a postoperative pain management program on organizational culture as well as in terms of resistance to change, in a complex health care setting. In the current study the unit was under organizational strain during the implementation. Albeit, the important discrepancy between the current and preferred organizational culture could imply that structural changes aren’t enough when implementing person-centred pain management structures and needs to be combined with relational aspects of change.
Clinical incident reporting behaviors and associated factors among health professionals in Dessie comprehensive specialized hospital, Amhara Region, Ethiopia: a mixed method study
Authors: Yalew Zemen Mengesha , Yitayew Yibeltal Asmamaw
Published: December 2021

Background

Understanding the type and causes of errors are necessary for the prevention of occurrence or reoccurrence. Therefore addressing the behavior of health professionals on reporting clinical incidents is crucial to create spontaneous knowledge from mistakes and enhance patient safety.

Method

A mixed type institution-based cross-sectional study design was conducted from March 1 - 30, 2020 in Dessie comprehensive specialized hospital among 319 and 18 participants for the quantitative and qualitative study, respectively. The professions and participants with their assigned proportions were selected using a simple random sampling technique. For quantitative and qualitative data, semi structured questionnaires and interviewer-guided questions were used to collect data, respectively. Finally, qualitative findings were used to supplement the quantitative result.

Result

The finding showed that the proportion of clinical incident reporting behavior among health professionals was 12.4%. Having training (AOR=3.6, 95% CI, 1.15-11.45), incident reporting help to minimize errors (AOR=2.8, 95% CI, 1.29-6.02), fear of legal penalty (AOR= 0.3, 95% CI, 0.13-0.82), and lack of feedback (AOR=0.3, 95% CI, 0.11-0.90) were identified as significant factors for clinical incident reporting behavior of the health professionals.

Conclusions

This study showed that the clinical incident reporting behavior of the health professionals was very low. Therefore health professionals should get training on clinical incident reporting and the hospital should have an incident reporting system and guideline.
Investigation of the effects of mTOR inhibitors rapamycin and everolimus in combination with carboplatin on canine malignant melanoma cells
Authors: Bernard Sarah , Poon Andrew C. , Tam Peyton M. , Mutsaers Anthony J.
Published: December 2021

Background

Malignant melanoma in dogs is considered to be largely resistant to conventional chemotherapy, although responses to carboplatin have been documented. Invasion and early metastasis are common features of certain melanoma subtypes that contribute to tumour progression despite aggressive local and systemic therapy. Upregulation of the PI3K/AKT/mTOR pathway has been observed in canine malignant melanoma and may represent a potential target for therapy. Rapamycin (sirolimus) and everolimus are commercially available small molecule inhibitors that target mTOR and therefore may have anticancer activity in canine melanoma. It was hypothesized that there is synergism between rapamycin or everolimus and platinum chemotherapy, and that combination drug treatment would inhibit target/downstream proteins involved in cell viability/proliferation and increase cell death in canine melanoma cells. It was further hypothesized that rapamycin or everolimus would impact metabolism by reducing glycolysis in these cells. Four canine melanoma cell lines were treated in vitro with rapamycin and everolimus as sole treatment or combined with carboplatin. Cell viability, apoptosis, target modulation, and glycolytic metabolism were evaluated by crystal violet colourimetric assay, Annexin V/PI flow cytometry, western blotting, and Seahorse bioanalyzer, respectively.

Results

When combined with carboplatin chemotherapy, rapamycin or everolimus treatment was overall synergistic in reducing cell viability. Carboplatin-induced apoptosis was noted at 72 h after treatment compared to the vehicle control. Levels of phosphorylated mTOR were reduced by rapamycin and everolimus in all four cell lines, but activation of the downstream protein p70S6K was not consistently reduced by treatment in two of the cell lines. Both mTOR inhibitors decreased the extracellular acidification rate of canine melanoma cells, indicating reduced cancer cell glycolytic activity.

Conclusions

Inhibition of mTOR by rapalogs, such as rapamycin and everolimus combined with carboplatin chemotherapy may have activity in canine melanoma. Future mechanistic investigation is warranted, including in vivo assessment of this combination therapy.
CCNI2 promotes the progression of human gastric cancer through HDGF
Authors: Chen Wenchao , Zhou Yang , Wu Gang , Sun Peichun
Published: December 2021

Background

Gastric cancer is a highly aggressive malignant tumor with heterogeneity and is still a global health problem. The present study aimed to investigate the role of Cyclin I-like (CCNI2) in the regulation of phenotype and tumorigenesis, as well as its underlying mechanisms.

Method

The expression profile of CCNI2 in gastric cancer was determined based on The Cancer Genome Atlas (TCGA) database and immunohistochemical staining. The effects of altered CCNI2 expression on the biological phenotypes such as proliferation, clone formation, apoptosis and migration of gastric cancer cell lines BGC-823 and SGC-7901 were investigated. Mice xenograft models were established to reveal the role of CCNI2 knockdown on tumorigenesis. The potential mechanism of CCNI2 regulating gastric cancer was preliminarily determined by RNA sequencing.

Result

CCNI2 was abundantly expressed in gastric cancer and was positively correlated with pathological stage. Knockdown of CCNI2 slowed down the malignant progression of gastric cancer by inhibiting tumor cell proliferation, increasing the susceptibility to apoptosis and suppressing migration. Moreover, downregulation of CCNI2 attenuated the ability of gastric cancer cells to form tumors in mice. Additionally, there was an interaction between CCNI2 and transcription factor hepatoma-derived growth factor (HDGF) in SGC-7901 cells. Knockdown of CCNI2 alleviated the promoting effects of HDGF overexpression in gastric cancer cells.

Conclusions

CCNI2 promoted the progression of human gastric cancer through HDGF, which drew further interest regarding its clinical application as a potential therapeutic target.
Aloperine inhibits the progression of non-small-cell lung cancer through the PI3K/Akt signaling pathway
Authors: Liu Fujuan , Liu Tao , Li Haiying
Published: December 2021

Background

Lung cancer has become the leading cause of cancer-related death worldwide and non‐small‐cell lung cancer (NSCLC) accounts for approximately 85% of cases. Aloperine (ALO), an alkaloid active natural component from S. alopecuroide, has been found to exhibit anti-inflammatory, anti-tumor and anti-viral activity. However, Whether ALO exerts anti-tumor function on NSCLC remains poorly understood, and the underlying mechanisms remain unknown.

Methods

The CCK-8, colony formation, cell apoptosis with flow cytometry, wound healing and transwell cell invasion assays, were used to analyze the tumor progression of H1299 and A549 cells treated with ALO in vitro, and the xenograft model was constructed to assess the effect of ALO in vivo. The expression of protein was detected by Western blotting.

Results

ALO suppressed the cell proliferation, self-renewal, migration and invasion, induced apoptosis in A549 and H1299 cell. Furthermore, ALO significantly enhanced the level of cytochrome c in cytosol, and resulted in the dramatical increased levels of the cleaved caspase-3, caspased-9 and PARP. ALO also inhibited the expression of MMP-2 and MMP-9. Additionally, ALO also reduced p-AKT and p-mTOR to attenuate the PI3K/AKT signaling pathway.

Conclusion

This study unveils a rationale for ALO through PI3K/Akt signaling pathway affecting the cell progression such as cell growth, apoptosis and invasion, and ALO acts as a potential chemotherapeutic agent for NSCLC.
Emerging role of m6A methylation modification in ovarian cancer
Authors: Chang Lin-Lin , Xu Xia-Qing , Liu Xue-Ling , Guo Qian-Qian , Fan Yan-Nan , He Bao-Xia , Zhang Wen-Zhou
Published: December 2021

m6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC.

Graphical Abstract
Household and individual level risk factors associated with declining malaria incidence in Meghalaya, India: implications for malaria elimination in low-endemic settings
Authors: Sarkar Rajiv , Kessler Anne , Mawkhlieng Bandapkupar , Sullivan Steven A. , Wilson Mark L. , Carlton Jane M. , Albert Sandra
Published: December 2021

Background

A detailed analysis of household and individual level Plasmodium infection patterns in two low-endemic districts of Meghalaya was undertaken to better understand the epidemiology of malaria in northeast India.

Methods

Socio-demographic and behavioural information from residents (aged 1–69 years) of households were collected through pre-tested, questionnaire conducted in 2018 and 2019. Blood samples collected from participants were tested for Plasmodium falciparum and/or Plasmodium vivax infection using rapid diagnostic test, microscopy and PCR. Plasma samples from a subset of participants were analysed for antibodies against thirteen P. falciparum and four P. vivax antigens. Associations between household and individual level risk factors, and Plasmodium infections were evaluated using multilevel logistic regression models.

Results

A total of 2753 individuals from 827 households were enrolled in 2018, and 834 individuals from 222 households were enrolled in 2019. Of them, 33 (1.2%) were positive by PCR for P. falciparum in 2018 and none were positive for P. vivax. In 2019, no PCR-positive individuals were detected. All, but one, infections were asymptomatic; all 33 infections were sub-microscopic. Reported history of malaria in the past 12 months (OR = 8.84) and history of travel in the past 14 days (OR = 10.06) were significantly associated with Plasmodium infection. A significant trend of increased seropositivity with age was noted for all 17 antigens. Although adults (≥ 18 years) consistently had the highest seropositivity rates, a sizeable proportion of under-five children were also found to be seropositive. Almost all individuals (99.4%) reported sleeping under an insecticide-treated bed-net, and household indoor residual spray coverage in the 12 months preceding the survey was low (23%). Most participants correctly identified common signs and symptoms of malaria, i.e., fever (96.4%), headache (71.2%), chills (83.2%) and body-ache (61.8%). Almost all participants (94.3%) used government-provided services for treatment of malaria.

Conclusion

This study explored the epidemiology of malaria in two communities in Meghalaya, India, in the context of declining transmission. The presence of widespread asymptomatic infections and seropositivity among under-five children suggest that low-level Plasmodium transmission persists in this region. Implications of the study findings for malaria elimination efforts in low-transmission settings are discussed.
Self-assembled nanoparticles containing photosensitizer and polycationic brush for synergistic photothermal and photodynamic therapy against periodontitis
Authors: Shi Enyu , Bai Liya , Mao Lujia , Wang Hanping , Yang Xiaoying , Wang Yinsong , Zhang Mingming , Li Changyi , Wang Yue
Published: December 2021

Background

Periodontitis is a chronic inflammatory disease in oral cavity owing to bacterial infection. Photothermal therapy (PTT) and photodynamic therapy (PDT) have many advantages for antibacterial treatment. As an excellent photosensitizer, indocyanine green (ICG) shows prominent photothermal and photodynamic performances. However, it is difficult to pass through the negatively charged bacterial cell membrane, thus limiting its antibacterial application for periodontitis treatment.

Results

In this work, self-assembled nanoparticles containing ICG and polycationic brush were prepared for synergistic PTT and PDT against periodontitis. First, a star-shaped polycationic brush poly(2-(dimethylamino)ethyl methacrylate) (sPDMA) was synthesized via atom transfer radical polymerization (ATRP) of DMA monomer from bromo-substituted β-cyclodextrin initiator (CD-Br). Next, ICG was assembled with sPDMA to prepare ICG-loaded sPDMA (sPDMA@ICG) nanoparticles (NPs) and the physicochemical properties of these NPs were characterized systematically. In vitro antibacterial effects of sPDMA@ICG NPs were investigated in porphyromonas gingivalis (Pg), one of the recognized periodontitis pathogens. A ligature-induced periodontitis model was established in Sprague–Dawley rats for in vivo evaluation of anti-periodontitis effects of sPDMA@ICG NPs. Benefiting from the unique brush-shaped architecture of sPDMA polycation, sPDMA@ICG NPs significantly promoted the adsorption and penetration of ICG into the bacterial cells and showed excellent PTT and PDT performances. Both in vitro and in vivo, sPDMA@ICG NPs exerted antibacterial and anti-periodontitis actions via synergistic PTT and PDT.

Conclusions

A self-assembled nanosystem containing ICG and polycationic brush has shown promising clinical application for synergistic PTT and PDT against periodontitis.

Graphical Abstract
Exploration of the value of progesterone and progesterone/estradiol ratio on the hCG trigger day in predicting pregnancy outcomes of PCOS patients undergoing IVF/ICSI: a retrospective cohort study
Authors: Yang Yiqing , Liu Bowen , Wu Gengxiang , Yang Jing
Published: December 2021

Background

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with the disorders of estrogen(E2) and progesterone(P) secretion. The purpose of this study was to evaluate the association between the progesterone level or progesterone/estradiol(P/E2) ratio on human chorionic gonadotropin (hCG) trigger day and the outcome of in vitro fertilization in PCOS patients and explore the value of progesterone and P/E2 ratio for predicting the clinical pregnancy.

Methods

The clinical data of 1254 PCOS patients who satisfied the inclusion criteria were retrospectively analyzed, including baseline characteristics such as age, body mass index, basal sex hormone levels, et al., as well as ovarian stimulation data and clinic outcome.

Results

The number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001) was greater in the high progesterone group (progesterone ≥ 0.92 ng/mL). In the high P/E2 group(P/E2 ratio ≥ 0.3), the number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001), as well as the rate of high-quality embryos (P = 0.040) were significantly decreased. In ultralong GnRH agonist protocol, the implantation rate(P < 0.001), hCG positive rate (P < 0.001), clinical pregnancy rate (P < 0.001) and live birth rate (P < 0.001) were all significantly higher than long GnRH agonist protocol and GnRH antagonist protocol. The clinical pregnancy rate of high progesterone group was significantly lower than that of low progesterone group in ultralong GnRH agonist (P = 0.008). The progesterone level could be used as an indicator to predict the positive clinical pregnancy (long GnRH agonist: P = 0.001; ultralong GnRH agonist: P < 0.001) except in cycles using GnRH antagonist (P = 0.169). In the ultralong GnRH agonist, the value of progesterone level in the prediction of clinical pregnancy was significantly higher than that of the P/E2 ratio (P = 0.021).

Conclusions

In PCOS patients, the progesterone level is associated with clinical pregnancy rate while P/E2 ratio is not. In subgroup analysis using three different COS protocols, a significant association between progesterone level and clinical pregnancy rate can be observed in the long GnRH agonist protocol and ultralong GnRH agonist protocol. The progesterone level is significantly better than the P/E2 ratio in predicting the pregnancy outcome of PCOS patients, especially in ultralong GnRH agonist cycles.
The impact on renal function after long-term use of anticoagulants in atrial fibrillation patients
Authors: Lee Wei-Chieh , Lee Pai-Wei , Wu Po-Jui , Fang Yen-Nan , Chen Huang-Chung , Lin Yu-Sheng , Fang Hsiu-Yu , Chang Shang-Hung , Liu Ping-Yen , Chen Mien-Cheng
Published: December 2021

Objective

Long-term oral anticoagulant should be considered or recommended in patients with atrial fibrillation (AF) and CHA2DS2VASc score ≥ 1 for stroke prevention. Warfarin and different direct oral anticoagulants (DOACs) are metabolized differently by the kidney. The impact on renal function after long-term use of anticoagulants in the patients with AF remains unclear. This study aimed to compare DOACs and warfarin’s impact on the decline in renal function from a large cohort with AF.

Methods

This study included patients with nonvalvular AF from 2000 to 2018, mainly through the medical history (ICD code) of the Chang Gung Research Database. Baseline estimated glomerular filtration rate (eGFR), follow-up eGFR and the change in eGFR between 2-year eGFR and baseline eGFR were compared between different DOACs and warfarin after propensity score matching. The primary study endpoint was acute kidney injury (AKI).

Results

3657 patients were enrolled in this study and the mean observation time was 3.3 ± 0.9 years. During the observation period, there was a significantly higher incidence of AKI during follow-up in the warfarin group than in the different DOAC groups before and after propensity score matching (before: warfarin vs. DOAC: 9.2% vs. 5.2%, p <  0.001; after: warfarin vs. DOAC: 8.9% vs. 4.4%, p <  0.001). There was no difference in the incidence of AKI between dabigatran group and anti-factor Xa inhibitor group after propensity score matching. The incidence of AKI was similar among rivaroxaban, apixaban and edoxaban groups after propensity score matching. The change in eGFR between 2-year eGFR and baseline eGFR did not differ between the warfarin and DOAC groups after propensity score matching (warfarin vs. DOAC: − 1.27 ± 20.32 vs. -1.94 ± 17.24 mL/min/1.73 m2, p = 0.461).

Conclusions

During the mean observation time of 3.3 ± 0.9 years, warfarin was associated with a higher incidence of AKI compared with DOACs. The decline in renal function did not differ among warfarin and different DOAC groups.
Measuring health science research and development in Africa: mapping the available data
Authors: Wenham Clare , Wouters Olivier , Jones Catherine , Juma Pamela A. , Mijumbi-Deve Rhona M. , Sobngwi-Tambekou Joëlle L. , Parkhurst Justin
Published: December 2021

Background

In recent years there have been calls to strengthen health sciences research capacity in African countries. This capacity can contribute to improvements in health, social welfare and poverty reduction through domestic application of research findings; it is increasingly seen as critical to pandemic preparedness and response. Developing research infrastructure and performance may reduce national economies’ reliance on primary commodity and agricultural production, as countries strive to develop knowledge-based economies to help drive macroeconomic growth. Yet efforts to date to understand health sciences research capacity are limited to output metrics of journal citations and publications, failing to reflect the complexity of the health sciences research landscape in many settings.

Methods

We map and assess current capacity for health sciences research across all 54 countries of Africa by collecting a range of available data. This included structural indicators (research institutions and research funding), process indicators (clinical trial infrastructures, intellectual property rights and regulatory capacities) and output indicators (publications and citations).

Results

While there are some countries which perform well across the range of indicators used, for most countries the results are varied—suggesting high relative performance in some indicators, but lower in others. Missing data for key measures of capacity or performance is also a key concern. Taken as a whole, existing data suggest a nuanced view of the current health sciences research landscape on the African continent.

Conclusion

Mapping existing data may enable governments and international organizations to identify where gaps in health sciences research capacity lie, particularly in comparison to other countries in the region. It also highlights gaps where more data are needed. These data can help to inform investment priorities and future system needs.
γ-Enolase enhances Trk endosomal trafficking and promotes neurite outgrowth in differentiated SH-SY5Y cells
Authors: Pišlar Anja , Kos Janko
Published: December 2021

Background

Neurotrophins can activate multiple signalling pathways in neuronal cells through binding to their cognate receptors, leading to neurotrophic processes such as cell survival and differentiation. γ-Enolase has been shown to have a neurotrophic activity that depends on its translocation towards the plasma membrane by the scaffold protein γ1-syntrophin. The association of γ-enolase with its membrane receptor or other binding partners at the plasma membrane remains unknown.

Methods

In the present study, we used immunoprecipitation and immunofluorescence to show that γ-enolase associates with the intracellular domain of the tropomyosin receptor kinase (Trk) family of tyrosine kinase receptors at the plasma membrane of differentiated SH-SY5Y cells.

Results

In differentiated SH-SY5Y cells with reduced expression of γ1-syntrophin, the association of γ-enolase with the Trk receptor was diminished due to impaired translocation of γ-enolase towards the plasma membrane or impaired Trk activity. Treatment of differentiated SH-SY5Y cells with a γ-Eno peptide that mimics γ-enolase neurotrophic activity promoted Trk receptor internalisation and endosomal trafficking, as defined by reduced levels of Trk in clathrin-coated vesicles and increased levels in late endosomes. In this way, γ-enolase triggers Rap1 activation, which is required for neurotrophic activity of γ-enolase. Additionally, the inhibition of Trk kinase activity by K252a revealed that increased SH-SY5Y cell survival and neurite outgrowth mediated by the γ-Eno peptide through activation of signalling cascade depends on Trk kinase activity.

Conclusions

These data therefore establish the Trk receptor as a binding partner of γ-enolase, whereby Trk endosomal trafficking is promoted by γ-Eno peptide to mediate its neurotrophic signalling.

Graphical Abstract
Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis
Authors: Lamo-Espinosa José María , Prósper Felipe , Blanco Juan F. , Sánchez-Guijo Fermín , Alberca Mercedes , García Verónica , González-Vallinas Margarita , García-Sancho Javier
Published: December 2021

Knee osteoarthritis is the most prevalent joint disease and a frequent cause of pain, functional loss and disability. Conventional treatments have demonstrated only modest clinical benefits whereas cell-based therapies have shown encouraging results, but important details, such as dose needed, long-term evolution or number of applications required are scarcely known. Here we have reanalyzed results from two recent pilot trials with autologous bone marrow-derived mesenchymal stromal cells using the Huskisson plot to enhance quantification of efficacy and comparability. We find that cell doses of 10, 40 and 100 million autologous cells per knee provided quite similar healing results and that much of the effect attained 1 year after cell application remained after 2 and 4 years. These results are encouraging because they indicate that, apart from safety and simplicity: (i) the beneficial effect is both significant and sizeable, (ii) it can be achieved with a single injection of cells, and (iii) the effect is perdurable for years.

Trial registration: EudraCT 2009-017405-11; NCT02123368. Registered 25 April 2014—Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT02123368?term=02123368&draw=2&rank=1
Physical activity dimensions after stroke: patterns and relation with lower limb motor function
Authors: Braakhuis Hanneke E. M. , Berger Monique A. M. , Regterschot Ruben G. R. H. , van Wegen Erwin E. H. , Selles Ruud W. , Ribbers Gerard M. , Bussmann Johannes B. J. ,   the PROFITS research group, Meskers Carel , Kwakkel Gert , van Wegen Erwin E. H. , Nijland Rinske , Andinga Aukje , Zonjee Valentijn , Koolstra-Rutgers Muriel , van den Berg-Vos Renske
Published: December 2021

Background

Stroke survivors show deteriorated physical functioning and physical activity levels. Physical activity levels of stroke survivors are generally low. It is increasingly recognized that physical activity is a multidimensional construct that cannot be captured in a single outcome. In-depth insight into multidimensional physical activity patterns may guide the development and timing of targeted rehabilitation interventions. This longitudinal cohort study explored how multidimensional physical activity outcomes develop during recovery in the subacute phase after stroke and if changes in physical activity were correlated to recovery of lower limb motor function.

Methods

Patients were recruited during inpatient rehabilitation. At 3, 12, and 26 weeks post-onset, motor function was measured by the Fugl-Meyer Lower Extremity Assessment (FMA-LE). Physical activity was measured with the Activ8 accelerometer in multiple outcomes: counts per minute during walking (CPMwalking; a measure of Intensity), number of active bouts (Frequency), mean length of active bouts (Distribution) and % of waking time in upright positions (Duration). Generalized estimating equations (GEE) were used to study changes in physical activity over time and the relation with the change in lower limb motor recovery.

Results

Thirty-nine patients (age 56 ± 9, 77% male, 89% ischemic stroke) were included. GEE models showed a significant main effect of time for PA Intensity (+ 13%, p = 0.007) and Duration (+ 64%, p = 0.012) between 3 and 12 weeks. Motor function did not show a significant effect in all PA models across the 3 timepoints (p > 0.020). A significant interaction effect of time × motor function was observed (p < 0.001).

Conclusions

Patterns of PA recovery depend on the PA dimensions: PA Intensity and Duration increased mostly between 3 and 12 weeks post-stroke, whereas Frequency and Distribution did not show substantial changes. Further, no strong associations with motor recovery and high inter-individual variability were documented, which underlies the need to consider factors specific to the disease, the individual patient and the context.
Machine learning approaches for the genomic prediction of rheumatoid arthritis and systemic lupus erythematosus
Authors: Chung Chih-Wei , Hsiao Tzu-Hung , Huang Chih-Jen , Chen Yen-Ju , Chen Hsin-Hua , Lin Ching-Heng , Chou Seng-Cho , Chen Tzer-Shyong , Chung Yu-Fang , Yang Hwai-I , Chen Yi-Ming
Published: December 2021

Background

Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) are autoimmune rheumatic diseases that share a complex genetic background and common clinical features. This study’s purpose was to construct machine learning (ML) models for the genomic prediction of RA and SLE.

Methods

A total of 2,094 patients with RA and 2,190 patients with SLE were enrolled from the Taichung Veterans General Hospital cohort of the Taiwan Precision Medicine Initiative. Genome-wide single nucleotide polymorphism (SNP) data were obtained using Taiwan Biobank version 2 array. The ML methods used were logistic regression (LR), random forest (RF), support vector machine (SVM), gradient tree boosting (GTB), and extreme gradient boosting (XGB). SHapley Additive exPlanation (SHAP) values were calculated to clarify the contribution of each SNPs. Human leukocyte antigen (HLA) imputation was performed using the HLA Genotype Imputation with Attribute Bagging package.

Results

Compared with LR (area under the curve [AUC] = 0.8247), the RF approach (AUC = 0.9844), SVM (AUC = 0.9828), GTB (AUC = 0.9932), and XGB (AUC = 0.9919) exhibited significantly better prediction performance. The top 20 genes by feature importance and SHAP values included HLA class II alleles. We found that imputed HLA-DQA1*05:01, DQB1*0201 and DRB1*0301 were associated with SLE; HLA-DQA1*03:03, DQB1*0401, DRB1*0405 were more frequently observed in patients with RA.

Conclusions

We established ML methods for genomic prediction of RA and SLE. Genetic variations at HLA-DQA1, HLA-DQB1, and HLA-DRB1 were crucial for differentiating RA from SLE. Future studies are required to verify our results and explore their mechanistic explanation.
The effectiveness and safety of paediatric prehospital pain management: a systematic review
Authors: Abebe Yonas , Hetmann Fredrik , Sumera Kacper , Holland Matt , Staff Trine
Published: December 2021

Background

Clinically meaningful pain reduction with respect to severity and the adverse events of drugs used in prehospital pain management for children are areas that have not received sufficient attention. The present systematic review therefore aims to perform a comprehensive search of databases to examine the preferable drugs for prehospital pain relief in paediatric patients with acute pain, irrespective of aetiology.

Methods

The systematic review includes studies from 2000 and up to 2020 that focus on children’s prehospital pain management. The study protocol is registered in PROSPERO with registration no. CRD42019126699. Pharmacological pain management using any type of analgesic drug and in all routes of administration was included. The main outcomes were (1) measurable pain reduction (effectiveness) and (2) no occurrence of any serious adverse events. Searches were conducted in PubMed, Medline, Embase, CINAHL, Epistemonikos and Cochrane library. Finally, the risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist and a textual narrative analysis was performed due to the heterogeneity of the results.

Results

The present systematic review on the effectiveness and safety of analgesic drugs in prehospital pain relief in children identified a total of eight articles. Most of the articles reviewed identified analgesic drugs such as fentanyl (intranasal/IV), morphine (IV), methoxyflurane (inhalational) and ketamine (IV/IM). The effects of fentanyl, morphine and methoxyflurane were examined and all of the included analgesic drugs were evaluated as effective. Adverse events of fentanyl, methoxyflurane and ketamine were also reported, although none of these were considered serious.

Conclusion

The systematic review revealed that fentanyl, morphine, methoxyflurane and combination drugs are effective analgesic drugs for children in prehospital settings. No serious adverse events were reported following the administration of fentanyl, methoxyflurane and ketamine. Intranasal fentanyl and inhalational methoxyflurane seem to be the preferred drugs for children in pre-hospital settings due to their ease of administration, similar effect and safety profile when compared to other analgesic drugs. However, the level of evidence (LOE) in the included studies was only three or four, and further studies are therefore necessary.
Treatment of urinary incontinence in women with chronic obstructive pulmonary disease—a randomised controlled study
Authors: Haukeland-Parker Stacey , Frisk Bente , Spruit Martijn A. , Stafne Signe Nilssen , Johannessen Hege Hølmo
Published: December 2021

Background

Little is known regarding treatment of urinary incontinence (UI) in women with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore the efficacy of pelvic floor muscle training (PFMT) or cough-suppression techniques (CST) on UI in women with COPD.

Methods

A three-armed, two-centred, single-blinded, randomised controlled study was performed. Subjects were randomised to (a) PFMT for 16 weeks, (b) 2–3 educational sessions in CST, or (c) written information only. All participants completed questionnaires about UI, cough symptoms, and health status and underwent clinical examinations to evaluate the strength of the pelvic floor muscles and exercise capacity. Daily physical activity levels were measured using an activity monitor and lung function with spirometry. With a significance level of 5% and an 80% chance of detecting a significant difference between groups of 2.5 points on the ICIQ UI SF score, our sample size calculation showed that a total of 78 women, 26 in each group, was required to complete the study.

Results

During the period 2016 to 2018, 95 women were invited to the study. A total of 42 were recruited, three were excluded and 10 (24%) dropped out during the follow-up period. Mean ICIQ-UI SF total baseline score was 9.6 (range: 1–17) and 7.0 (range: 0–16) at follow-up. Changes in subjective UI as measured with the ICIQ-UI SF questionnaire were seen in the PFMT group and control group, but not in the CST group.

Conclusion

Due to the low number of available participants and recruitment difficulties including practical issues such as travel distance, lack of interest, poor state of health, and high number of comorbidities, our results are inconclusive. However, reduced subjective UI was observed in the PFMT and control groups with a trend towards best effect in the PFMT group. Screening for UI is advisable in all women with COPD to be able to identify and treat these women to reduce symptom burden and improve quality of life. Future studies should focus on barriers to recruitment as well as randomised controlled studies with larger sample sizes.

Trial registration

ClinicalTrials.gov NCT02614105. 25th November 2015.
Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomized controlled trial
Authors: Jiang Rong Cai , Wang Dong , Zhao Shi Guang , Wang Ren Zhi , Kang De Zhi , Zhu Xin Gen , Zhao Zong Mao , Wei Jun Ji , Huang Ying , Qu Yan , Sun Xiao Chuan , Ji Hong Ming , Jiang Xiao Chun , Liu Jin Fang , De Zhu Xi , Wang Jian Jun , Tian Ye , Gao Chuang , Wei Hui Jie , Zhang Shu , Quan Wei , Yue Shu Yuan , Lei Ping , Li Xian , Song Li Li , Anderson Craig S. , Zhang Jian Ning
Published: December 2021

Background

Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH.

Methods

The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days.

Discussion

This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH.

Trial registration

ChiCTR,ChiCTR1900021659. Registered on 3 March 2019,http://www.chictr.org.cn/showproj.aspx?proj=36157.
Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): protocol for identification of novel biomarkers via neurophysiology
Authors: Daskalakis Zafiris J. , McClintock Shawn M. , Hadas Itay , Kallioniemi Elisa , Zomorrodi Reza , Throop Alanah , Palmer Lucy , Farzan Faranak , Thorpe Kevin E. , Tamminga Carol , Blumberger Daniel M.
Published: December 2021

Background

Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood.

Methods/design

This neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity.

Discussion

ECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments.

Trial registration

ClinicalTrials.govNCT03191058. Registered on June 19, 2017.
Online supervised versus workplace corrective exercises for upper crossed syndrome: a protocol for a randomized controlled trial
Authors: Yaghoubitajani Zohreh , Gheitasi Mehdi , Bayattork Mohammad , Andersen Lars Louis
Published: December 2021

Background and objective

Musculoskeletal disorders (MSDs) including upper crossed syndrome (UCS) are considered as the leading cause of work-related issues worldwide among office workers. Therefore, the present study aims to evaluate the effect of workplace-based versus online-supervised home-based corrective exercises among office workers with UCS.

Methods and design

To this end, 45 subjects within the age range of 30–45 years are randomly assigned to three groups in the present parallel-group, randomized control trial using a pretest-posttest design. These groups include the subjects who receive online-supervised exercise and workplace exercise containing three sessions of intervention for 8 weeks and the control group receives no intervention while performing routine activities. The primary outcome variables are neck-shoulder pain (NSP) and consequent sick leave due to NSP, followed by alignment, workability, and the surface electromyography of upper, middle, and lower trapezius (UT, MT, and LT), sternocleidomastoid (SCM), and serratus anterior (SA) as the secondary variables.

Discussion

The present study seeks to assess the effect of workplace versus online-supervised corrective exercise interventions among 45 office workers suffering from UCS. It is expected to improve and reduce the related symptoms including postural malalignment and imbalance muscles after 8 weeks of corrective exercises. If effective, the findings may lead to adherence and work performance among the office workers, and individuals subjected to UCS can use the benefits of an online-supervised intervention. In addition, the findings may be useful in different workplaces as the evidence for employers to benefit from the reduction in the related costs and side effects of work-related neck/shoulder disorders including work disability, productivity loss, time expense, social insurance, work absenteeism, and treatment costs. Finally, clinicians and corrective exercise therapists can consider it as a clinical based-evidence intervention for their further actions.

Trial registration

Iranian Registry of Clinical Trials IRCT20200729048249N1. Registered on 5 October 2020 (https://en.irct.ir/user/trial/49992/view)
Feasibility of remote neurocognitive assessment: pandemic adaptations for a clinical trial, the Cognition and Obstructive Sleep Apnea in Parkinson’s Disease, Effect of Positive Airway Pressure Therapy (COPE-PAP) study
Authors: Lajoie Annie C. , Crane Joelle , Robinson Ann R. , Lafontaine Anne-Louise , Benedetti Andrea , Kimoff R. John , Kaminska Marta
Published: December 2021

Background

The COVID-19 pandemic poses challenges for timely outcome assessment in randomized clinical trials (RCT). Our aim was to describe our remote neurocognitive testing (NCT) protocol administered by telephone in patients with Parkinson’s disease (PD) and obstructive sleep apnea (OSA).

Methods

We studied PD patients with OSA and Montreal Cognitive Assessment (MoCA) score ≤ 27 participating in a RCT assessing OSA treatment impact on cognition. Trial outcomes included change in MoCA and specific cognitive domains from baseline to 3 and 6 months. With COVID19 pandemic-related restrictions, 3-month visits were converted from in-person to telephone administration with materials mailed to participants for compatible tests and retrieved by courier the same day. In exploratory analyses, we compared baseline vs. 3-month results in the control arm, which were not expected to change significantly (test-re-test), using a paired t-test and assessed agreement with the intraclass correlation coefficient (ICC).

Results

Seven participants were approached and agreed to remote NCT at 3-month follow-up. Compared to the in-person NCT control arm group, they were younger (60.6 versus 70.6 years) and had a shorter disease course (3.9 versus 9.2 years). Remote NCT data were complete. The mean test-retest difference in MoCA was similar for in-person and remote NCT control-arm groups (between group difference − 0.69; 95%CI − 3.67, 2.29). Agreement was good for MOCA and varied for specific neurocognitive tests.

Conclusion

Telephone administration of the MoCA and a modified neurocognitive battery is feasible in patients with PD and OSA. Further validation will require a larger sample size.