bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients’ impressions of after-hours house-call services during the COVID-19 pandemic in Japan: a questionnaire-based observational study
Authors: Morita Kojiro , Inokuchi Ryota , Jin Xueying , Ishikawa Masatoshi , Tamiya Nanako
Published: September 2021

Background

Access to healthcare has been strongly affected by the coronavirus disease 2019 (COVID-19) pandemic, which has raised concerns about the increased risk of delays in receiving medical care. This study aimed to assess the patients’ impressions of after-hour house-call (AHHC) medical services during the COVID-19 pandemic using a patient questionnaire.

Methods

This was a cross-sectional observational study of anonymized medical record data and internet-based questionnaires from patients who used AHHC medical services from April 2020 to January 2021. We summarized the patients’ impressions of AHHC medical services during the COVID-19 pandemic stratified by patient characteristics. The questions of the questionnaire were as follows: (i) Did you use the AHHC medical services because you suspected you had COVID-19 infection? (ii) Do you feel that the use of AHHC medical services has helped prevent transmission of COVID-19? (iii) What action would you have taken in the absence of AHHC medical services?

Results

A total of 1802 patients responded to the questionnaire (response rate: 11.3%).

First, 700 (40.8%) of the responders indicated that they had used AHHC medical services because of suspicion of COVID-19. Second, most responders (88.8%) felt that AHHC medical services prevented transmission of COVID-19. Third, 774 (43.0%) of the responders considered that they would have visited an emergency department or called an ambulance if AHHC medical services had not been used. Furthermore, 411 (22.8%) of the responders indicated that they would remain at home or wait until working hours if AHHC medical services were not available despite having a condition that required emergency attention.

Conclusions

AHHC medical services may be one of the strategies for those who refrain from seeking healthcare services, thus reducing the risk of delayed hospital visits during emergencies. Furthermore, AHHC medical services may also contribute to preventing transmission of COVID-19 by avoiding contact with other patients in the hospital.
A pragmatic randomized trial of a primary care antimicrobial stewardship intervention in Ontario, Canada
Authors: McIsaac Warren , Kukan Sahana , Huszti Ella , Szadkowski Leah , O’Neill Braden , Virani Sophia , Ivers Noah , Lall Rosemarie , Toor Navsheer , Shah Mruna , Alvi Ruby , Bhatt Aashka , Nakamachi Yoshiko , Morris Andrew M.
Published: September 2021

Background

More than 90% of antibiotics are prescribed in primary care, but 50% may be unnecessary. Reducing unnecessary antibiotic overuse is needed to limit antimicrobial resistance. We conducted a pragmatic trial of a primary care provider-focused antimicrobial stewardship intervention to reduce antibiotic prescriptions in primary care.

Methods

Primary care practitioners from six primary care clinics in Toronto, Ontario were assigned to intervention or control groups to evaluate the effectiveness of a multi-faceted intervention for reducing antibiotic prescriptions to adults with respiratory and urinary tract infections. The intervention included provider education, clinical decision aids, and audit and feedback of antibiotic prescribing. The primary outcome was total antibiotic prescriptions for these infections. Secondary outcomes were delayed prescriptions, prescriptions longer than 7 days, recommended antibiotic use, and outcomes for individual infections. Generalized estimating equations were used to estimate treatment effects, adjusting for clustering by clinic and baseline differences.

Results

There were 1682 encounters involving 54 primary care providers from January until May 31, 2019. In intervention clinics, the odds of any antibiotic prescription was reduced 22% (adjusted Odds Ratio (OR) = 0.78; 95% Confidence Interval (CI) = 0.64.0.96). The odds that a delay in filling a prescription was recommended was increased (adjusted OR=2.29; 95% CI=1.37, 3.83), while prescription durations greater than 7 days were reduced (adjusted OR=0.24; 95% CI=0.13, 0.43). Recommended antibiotic use was similar in control (85.4%) and intervention clinics (91.8%, p=0.37).

Conclusions

A community-based, primary care provider-focused antimicrobial stewardship intervention was associated with a reduced likelihood of antibiotic prescriptions for respiratory and urinary infections, an increase in delayed prescriptions, and reduced prescription durations.

Trial registration

clinicaltrials.gov (NCT03517215).
A CTLA-4 blocking strategy based on Nanobody in dendritic cell-stimulated cytokine-induced killer cells enhances their anti-tumor effects
Authors: Wang Wu , Wang Xi , Yang Wenli , Zhong Kai , He Na , Li Xuexia , Pang Yanyang , Lu Zi , Liu Aiqun , Lu Xiaoling
Published: September 2021

Background

Cytokine-induced killer cells induced with tumor antigen-pulsed dendritic cells (DC-CIK) immunotherapy is a promising strategy for the treatment of malignant tumors. However, it sefficacy is restricted by the immunosuppression, which is mediated by the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathway. In order to overcome the negative co-stimulation from these T cells, we screened a nanobody targeted for CTLA-4 (Nb36) and blocked the CTLA-4 signaling with Nb36.

Methods

Peripheral blood mononuclear cells (PBMCs) were collected from healthy donors to beused to induce CIK cells in vitro, after which they were co-cultured with DC cells that had received tumor antigens. In addition, we tested whether blocking CTLA-4 signaling with Nb36 could promote in vitro DC-CIK cells proliferation, pro-inflammatory cytokine production and cytotoxicity, or not. For the in vivo experiments, we constructed a subcutaneously transplanted tumor model and placed it in NOD/SCID mice to verify the anti-tumor effect of this therapy.

Results

After stimulation with Nb36, the DC-CIK cells presented enhanced proliferation and production of IFN-γ in vitro, which strengthened the killing effect on the tumor cells. For the in vivo experiments, it was found that Nb36-treated DC-CIK cells significantly inhibited the growth of subcutaneously transplanted livercancer tumors, as well as reduced the tumor weight and prolonged the survival of tumor-bearing NOD/SCID mice.

Conclusions

Our findings demonstrated that in response to CTLA-4 specific nanobody stimulation, DC-CIK cells exhibited a better anti-tumor effect. In fact, this Nb-based CTLA-4 blocking strategy achieved an anti-tumor efficacy close to that of monoclonal antibodies. Our findings suggest that DC-CIK cells + Nb36 have the potential to treat malignant tumors through in vivo adoptive therapy.
Infrequent RAS mutation is not associated with specific histological phenotype in gliomas
Authors: Makino Yasuhide , Arakawa Yoshiki , Yoshioka Ema , Shofuda Tomoko , Minamiguchi Sachiko , Kawauchi Takeshi , Tanji Masahiro , Kanematsu Daisuke , Nonaka Masahiro , Okita Yoshiko , Kodama Yoshinori , Mano Masayuki , Hirose Takanori , Mineharu Yohei , Miyamoto Susumu , Kanemura Yonehiro
Published: September 2021

Background

Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas.

Methods

This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis.

Results

RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology.

Conclusion

RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.
Ontario adults’ health behaviors, mental health, and overall well-being during the COVID-19 pandemic
Authors: Shillington Katie J. , Vanderloo Leigh M. , Burke Shauna M. , Ng Victor , Tucker Patricia , Irwin Jennifer D.
Published: September 2021

Background

Public health measures such as physical distancing and work-from-home initiatives have been implemented to slow the spread of COVID-19. These measures may also be associated with unhealthy lifestyle behaviors, which could be particularly problematic for those already at highest risk for losing years of healthy life due to chronic disease (i.e., 30–59-year-olds). The purpose of this paper is two-fold: (1) to provide an overview of Ontario adults’ health behaviors (i.e., physical activity, sedentary behaviors, and dietary intake), mental health, and well-being during the first few months of the COVID-19 pandemic (April–July 2020); and (2) to explore the difference between physical activity and various health behaviors (i.e., well-being, mental health, and dietary intake).

Methods

As a part of a larger, longitudinal study, participants completed an online survey that included demographic information, the Global Physical Activity Questionnaire, Starting the Conversation, the Mental Health Inventory, and the Personal Wellbeing Index-Adult. Data analyses involved computing measures of central tendency and dispersion for demographic characteristics and tools followed by descriptive statistics. Separate independent t-tests were conducted to investigate the difference between physical activity status and well-being, mental health, and dietary intake.

Results

A total of 2157 Ontarians completed an online survey. Descriptive statistics indicated that respondents met physical activity and sedentary behavior guidelines, reported double the amount of recommended recreational screen time, practiced moderately healthy dietary behaviors, experienced mental health problems, and scored below “normal” in some well-being domains.

Conclusion

As the end of the COVID-19 pandemic is currently unknown, its associated restrictions and society changes may influence adults’ behaviors in both the short- and longer-term. As such, our findings might provide immediate insight into the development of timely and evidence-informed health promotion and disease prevention strategies for Canadians, which could support adults’ health behaviors, mental health, and well-being during the COVID-19 pandemic and other, future pandemics.
Evaluation of the standard procedure for treatment of periprosthetic joint infections of total knee and hip arthroplasty: a comparison of the 2015 and 2020 census in total joint replacement centres in Germany
Authors: Osmanski-Zenk Katrin , Klinder Annett , Rimke Christina , Wirtz Dieter C. , Lohmann Christoph H. , Haas Holger , Kladny Bernd , Mittelmeier Wolfram
Published: September 2021

Background

There are different procedures for both, the diagnosis and the therapy of a periprosthetic joint infection (PJI), however, national or international guidelines for a standardised treatment regime are still lacking. The present paper evaluates the use of the predominant treatment protocols for PJI in certified total joint replacement centres (EPZ) in Germany based on an EndoCert questionnaire.

Materials and methods

The questionnaire was developed in cooperation with the EndoCert Certification Commission to survey the treatment protocols for septic revision arthroplasties in EPZ. Questions targeted the various treatment options including prosthesis preserving procedures (DAIR - Debridement, antibiotics, irrigation, and retention of the prosthesis), one-stage revision, two-stage revision, removal of the endoprosthesis and diagnostic sampling prior to re-implantation. All certified EPZ participated (n = 504) and the results from the current survey in 2020 were compared to data from a previous analysis in 2015.

Results

The number of centres that performed DAIR up to a maximum of 4 weeks and more than 10 weeks after index surgery decreased since 2015, while the number of centres that provided a one-stage revision as a treatment option increased (hip: + 6.3%; knee: + 6.6%). The majority of the centres (73.2%) indicated a 4–8 week period as the preferred interval between prosthesis removal and re-implantation in two-stage revision in hip as well as knee revisions. Centres with a higher number of revision surgeries (> 200 revisions/year), opted even more often for the 4–8 week period (92.3%). In two-stage revision the use of metal-based spacers with/without reinforcement with antibiotic-containing cement as an interim placeholder was significantly reduced in 2020 compared to 2015. There was also a clear preference for cemented anchoring in two-stage revision arthroplasty in the knee in 2020, whereas the majority of hip replacements was cementless. Additionally, in 2020 the number of samples for microbiological testing during the removal of the infected endoprosthesis increased and 72% of the centres took five or more samples. Overall, the number of EPZ with a standardised protocol for the procedure expanded from 2015 to 2020.

Conclusion

While there was a trend towards standardised therapeutic algorithms for PJI with more uniform choices among the centres in 2020 compared to 2015, the treatment often remains an individual decision. However, since a consistent treatment regime is of vital importance with an expected rise of total numbers of revision arthroplasties, uniform definitions with regard to comparability and standardisation are necessary for the further development of the EndoCert system.
Privacy and artificial intelligence: challenges for protecting health information in a new era
Authors: Murdoch Blake
Published: September 2021

Background

Advances in healthcare artificial intelligence (AI) are occurring rapidly and there is a growing discussion about managing its development. Many AI technologies end up owned and controlled by private entities. The nature of the implementation of AI could mean such corporations, clinics and public bodies will have a greater than typical role in obtaining, utilizing and protecting patient health information. This raises privacy issues relating to implementation and data security.

Main body

The first set of concerns includes access, use and control of patient data in private hands. Some recent public–private partnerships for implementing AI have resulted in poor protection of privacy. As such, there have been calls for greater systemic oversight of big data health research. Appropriate safeguards must be in place to maintain privacy and patient agency. Private custodians of data can be impacted by competing goals and should be structurally encouraged to ensure data protection and to deter alternative use thereof. Another set of concerns relates to the external risk of privacy breaches through AI-driven methods. The ability to deidentify or anonymize patient health data may be compromised or even nullified in light of new algorithms that have successfully reidentified such data. This could increase the risk to patient data under private custodianship.

Conclusions

We are currently in a familiar situation in which regulation and oversight risk falling behind the technologies they govern. Regulation should emphasize patient agency and consent, and should encourage increasingly sophisticated methods of data anonymization and protection.
Domiciliary dentistry clinics: a multiple case study in the province of Quebec, Canada
Authors: Makansi N. , Rousseau J. , Bedos C. ,   ACE-Dent Research Group, Gauthier Linda , Morissette Laurent , Ducharme Isabelle , Savage Claire , Esfandiari Shahrokh , Hovey Richard , Macdonald Mary Ellen , Nicolau Belinda , Lévesque Martine , Farrell Kim , Thomson Tammy , Apelian Nareg , Brondani Mario , Girard Félix , Dawson Aimée , Vergnes Jean-Noel , Blaizot Alessandra
Published: September 2021

Background

The demand for more flexible and person-centered models of oral healthcare delivery is increasing and while mobile and domiciliary dental services have the potential to increase access to oral healthcare among dependent elderly and people with disabilities; the uptake of this service model by dentists remains low. Therefore, the aim of this study was to understand how existing domiciliary dental services operate within a particular context.

Methods

We used a qualitative descriptive multiple case study design. We studied three independent domiciliary dentistry clinics in the province of Quebec, Canada. We completed observations of 27 domiciliary visits, four of which were in private homes and the remaining 23 in LTCFs. We also conducted semi-structured interviews with dental professionals, patients, and caregivers. We performed a qualitative content analysis using a deductive/inductive coding framework.

Results

We presented a detailed description of the physical and service features of the studied cases. Physical features included the set-up of the mobile clinics, the portable equipment used, and the domiciliary locations of visits. For service features, we described the roles, attitudes, and interactions among those involved on both the providers’ and recipients’ sides, as well as, the logistical and financial aspect of the domiciliary dental services.

Conclusions

Despite variations in setup and years of practice, the three mobile clinics had similar physical and service features. They also faced common logistic challenges but were able to provide services and respond to the high demand for domiciliary dental services. Additional research in different contexts would further contribute to building evidence-based models to help increase the uptake of this type of practice by current and future dental professionals.
Integrated early childhood development policy in Iran: a stakeholder analysis
Authors: Atashbahar Omolbanin , Sari Ali Akbari , Takian Amirhossein , Olyaeemanesh Alireza , Mohamadi Efat , Barakati Sayyed Hamed
Published: September 2021

Background

Many stakeholders are involved in the complicated process of policy making in integrated early childhood development (IECD). In other words, there are many challenges for IECD policy making in developing countries, including Iran. The aim of this study was to identify potential stakeholders and their interactions in IECD policy making in Iran.

Method

A mixed-methods study was conducted in two phases in 2018. First, forty semi-structured interviews and a review of IECD-related documents were conducted to identify potential stakeholders and their roles. Second, using a designed checklist, these stakeholders were assessed for power, interest, and position in IECD policy making. Then, a map of stakeholders and a three-dimensional stakeholder analysis figure were designed.

Results

The results of this study showed that various stakeholders, including governmental, semi-governmental, social, non-governmental and international organizations, potentially influence IECD policy in Iran. They were found to have diverse levels of power, interest and position in this regard, leading to their different impacts on the process. This diversity is assumed to have affected their levels of participation and support. Also, we found that the stakeholders with a high-power level do not have a high level of interest in, or support for, IECD policy. In general, organizational competition, complicated inter-sectoral nature of this process, insufficient budget, insufficient awareness about the importance of IECD, lack of priority given to IECD in relevant organizations, economical views rather than developmental perspectives, and lack of commitment among top managers are the reasons why this policy enjoys a low degree of support.

Conclusions

There are weaknesses in effective interactions and relationships among IECD policy stakeholders. This will lead to the lack of equal opportunities for optimal early childhood development. To improve this process, advocacy from high-level authorities of the organizations, negotiation with child-friendly groups, establishing a body to coordinate and oversee children’s affairs, using the capacity of non-governmental organizations, strengthening inter-sectoral collaboration by clarifying the roles and responsibilities of stakeholders and the relationships between them, and increasing public awareness can be helpful.
Insights into the evolutionary origin of the pineal color discrimination mechanism from the river lamprey
Authors: Wada Seiji , Kawano-Yamashita Emi , Sugihara Tomohiro , Tamotsu Satoshi , Koyanagi Mitsumasa , Terakita Akihisa
Published: September 2021

Background

Pineal-related organs in cyclostomes, teleosts, amphibians, and reptiles exhibit color opponency, generating antagonistic neural responses to different wavelengths of light and thereby sensory information about its “color”. Our previous studies suggested that in zebrafish and iguana pineal-related organs, a single photoreceptor cell expressing both UV-sensitive parapinopsin and green-sensitive parietopsin generates color opponency in a “one-cell system.” However, it remains unknown to what degree these opsins and the single cell-based mechanism in the pineal color opponency are conserved throughout non-mammalian vertebrates.

Results

We found that in the lamprey pineal organ, the two opsins are conserved but that, in contrast to the situation in other vertebrate pineal-related organs, they are expressed in separate photoreceptor cells. Intracellular electrophysiological recordings demonstrated that the parietopsin-expressing photoreceptor cells with Go-type G protein evoke a depolarizing response to visible light. Additionally, spectroscopic analyses revealed that parietopsin with 11-cis 3-dehydroretinal has an absorption maximum at ~570 nm, which is in approximate agreement with the wavelength (~560 nm) that produces the maximum rate of neural firing in pineal ganglion cells exposed to visible light. The vesicular glutamate transporter is localized at both the parietopsin- and parapinopsin-expressing photoreceptor terminals, suggesting that both types of photoreceptor cells use glutamate as a transmitter. Retrograde tracing of the pineal ganglion cells revealed that the terminal of the parietopsin-expressing cells is located close enough to form a neural connection with the ganglion cells, which is similar to our previous observation for the parapinopsin-expressing photoreceptor cells and the ganglion cells. In sum, our observations point to a “two-cell system” in which parietopsin and parapinopsin, expressed separately in two different types of photoreceptor cells,  contribute to the generation of color opponency in the pineal ganglion cells.

Conclusion

Our results indicate that the jawless vertebrate, lamprey, employs a system for color opponency that differes from that described previously in jawed vertebrates. From a physiological viewpoint, we propose an evolutionary insight, the emergence of pineal “one-cell system” from the ancestral “multiple (two)-cell system,” showing the opposite evolutionary direction to that of the ocular color opponency.
The stem rust fungus Puccinia graminis f. sp. tritici induces centromeric small RNAs during late infection that are associated with genome-wide DNA methylation
Authors: Sperschneider Jana , Jones Ashley W. , Nasim Jamila , Xu Bo , Jacques Silke , Zhong Chengcheng , Upadhyaya Narayana M. , Mago Rohit , Hu Yiheng , Figueroa Melania , Singh Karam B. , Stone Eric A. , Schwessinger Benjamin , Wang Ming-Bo , Taylor Jennifer M. , Dodds Peter N.
Published: September 2021

Background

Silencing of transposable elements (TEs) is essential for maintaining genome stability. Plants use small RNAs (sRNAs) to direct DNA methylation to TEs (RNA-directed DNA methylation; RdDM). Similar mechanisms of epigenetic silencing in the fungal kingdom have remained elusive.

Results

We use sRNA sequencing and methylation data to gain insight into epigenetics in the dikaryotic fungus Puccinia graminis f. sp. tritici (Pgt), which causes the devastating stem rust disease on wheat. We use Hi-C data to define the Pgt centromeres and show that they are repeat-rich regions (~250 kb) that are highly diverse in sequence between haplotypes and, like in plants, are enriched for young TEs. DNA cytosine methylation is particularly active at centromeres but also associated with genome-wide control of young TE insertions. Strikingly, over 90% of Pgt sRNAs and several RNAi genes are differentially expressed during infection. Pgt induces waves of functionally diversified sRNAs during infection. The early wave sRNAs are predominantly 21 nts with a 5′ uracil derived from genes. In contrast, the late wave sRNAs are mainly 22-nt sRNAs with a 5′ adenine and are strongly induced from centromeric regions. TEs that overlap with late wave sRNAs are more likely to be methylated, both inside and outside the centromeres, and methylated TEs exhibit a silencing effect on nearby genes.

Conclusions

We conclude that rust fungi use an epigenetic silencing pathway that might have similarity with RdDM in plants. The Pgt RNAi machinery and sRNAs are under tight temporal control throughout infection and might ensure genome stability during sporulation.
Competition-based screening helps to secure the evolutionary stability of a defensive microbiome
Authors: Worsley Sarah F. , Innocent Tabitha M. , Holmes Neil A. , Al-Bassam Mahmoud M. , Schiøtt Morten , Wilkinson Barrie , Murrell J. Colin , Boomsma Jacobus J. , Yu Douglas W. , Hutchings Matthew I.
Published: September 2021

Background

The cuticular microbiomes of Acromyrmex leaf-cutting ants pose a conundrum in microbiome biology because they are freely colonisable, and yet the prevalence of the vertically transmitted bacteria Pseudonocardia, which contributes to the control of Escovopsis fungus garden disease, is never compromised by the secondary acquisition of other bacterial strains. Game theory suggests that competition-based screening can allow the selective recruitment of antibiotic-producing bacteria from the environment, by providing abundant resources to foment interference competition between bacterial species and by using Pseudonocardia to bias the outcome of competition in favour of antibiotic producers.

Results

Here, we use RNA-stable isotope probing (RNA-SIP) to confirm that Acromyrmex ants can maintain a range of microbial symbionts on their cuticle by supplying public resources. We then used RNA sequencing, bioassays, and competition experiments to show that vertically transmitted Pseudonocardia strains produce antibacterials that differentially reduce the growth rates of other microbes, ultimately biassing the bacterial competition to allow the selective establishment of secondary antibiotic-producing strains while excluding non-antibiotic-producing strains that would parasitise the symbiosis.

Conclusions

Our findings are consistent with the hypothesis that competition-based screening is a plausible mechanism for maintaining the integrity of the co-adapted mutualism between the leaf-cutting ant farming symbiosis and its defensive microbiome. Our results have broader implications for explaining the stability of other complex symbioses involving horizontal acquisition.
Beam orientation optimization for coherent X-ray scattering from distributed deep targets
Authors: Breedlove Sophya , Badano Aldo
Published: September 2021

Background

Amyloid deposits in the temporal and frontal lobes in patients with Alzheimer’s disease make them potential targets to aid in early diagnosis. Recently, spectral small-angle X-ray scattering techniques have been proposed for interrogating deep targets such as amyloid plaques.

Results

We describe an optimization approach for the orientation of beams for deep target characterization. The model predicts the main features of scattering profiles from targets with varying shape, size and location. We found that increasing target size introduced additional smearing due to location uncertainty, and incidence angle affected the scattering profile by altering the path length or effective target size. For temporal and frontal lobe targets, beam effectiveness varied up to 2 orders of magnitude.

Conclusions

Beam orientation optimization might allow for patient-specific optimal paths for improved signal characterization.
Support mechanisms for research generation and application for postgraduate students in four universities in Uganda
Authors: Obuku E. A. , Apunyo R. , Mbabazi G. , Mafigiri D. K. , Karamagi C. , Sengooba F. , Lavis J. N. , Sewankambo N. K.
Published: September 2021

Background

A large proportion of postgraduate students the world over complete a research thesis in partial fulfilment of their degree requirements. This study identified and evaluated support mechanisms for research generation and utilization for masters’ students in health institutions of higher learning in Uganda.

Methods

This was a self-administered cross-sectional survey using a modified self-assessment tool for research institutes (m-SATORI). Postgraduate students were randomly selected from four medical or public health Ugandan universities at Makerere, Mbarara, Nkozi and Mukono and asked to circle the most appropriate response on a Likert scale from 1, where the “situation was unfavourable and/or there was a need for an intervention”, to 5, where the “situation was good or needed no intervention”. These questions were asked under four domains: the research question; knowledge production, knowledge transfer and promoting use of evidence. Mean scores of individual questions and aggregate means under the four domains were computed and then compared to identify areas of strengths and gaps that required action.

Results

Most of the respondents returned their questionnaires, 185 of 258 (71.7%), and only 79 of these (42.7%) had their theses submitted for examination. The majority of the respondents were male (57.3%), married or cohabiting (58.4%), and were medical doctors (71.9%) from Makerere University (50.3%). The domain proposal development for postgraduate research project had the highest mean score of 3.53 out of the maximum 5. Three of the four domains scored below the mid-level domain score of 3, that is, the situation is neither favourable nor unfavourable. Areas requiring substantial improvements included priority-setting during research question identification, which had the lowest mean score of 2.12. This was followed by promoting use of postgraduate research products, tying at mean scores of 2.28 each. The domain knowledge transfer of postgraduate research products had an above-average mean score of 2.75.

Conclusions

This study reports that existing research support mechanisms for postgraduate students in Uganda encourage access to supervisors and mentors during proposal development. Postgraduate students’ engagement with research users was limited in priority-setting and knowledge transfer. Since supervisors and mentors views were not captured, future follow-on research could tackle this aspect.
Comprehensive analysis of EMT-related genes and lncRNAs in the prognosis, immunity, and drug treatment of colorectal cancer
Authors: Yang Yang , Feng Mingyang , Bai LiangLiang , Liao Weiting , Zhou Kexun , Zhang Mengxi , Wu Qiuji , Wen Feng , Lei Wanting , Zhang Pengfei , Zhang Nan , Huang Jiaxing , Li Qiu
Published: September 2021

Background

EMT is an important biological process in the mechanism of tumor invasion and metastasis. However, there are still many unknowns about the specific mechanism of EMT in tumor. At present, a comprehensive analysis of EMT-related genes in colorectal cancer (CRC) is still lacking.

Methods

All the data were downloaded from public databases including TCGA database (488 tumor samples and 52 normal samples) as the training set and the GEO database (GSE40967 including 566 tumor samples and 19 normal samples, GSE12945 including 62 tumor samples, GSE17536 including 177 tumor samples, GSE17537 including 55 tumor samples) as the validation sets. One hundred and sixty-six EMT-related genes (EMT-RDGs) were selected from the Molecular Signatures Database. Bioinformatics methods were used to analyze the correlation between EMT-RDGs and CRC prognosis, metastasis, drug efficacy, and immunity.

Results

We finally obtained nine prognostic-related EMT-RDGs (FGF8, NOG, PHLDB2, SIX2, SNAI1, TBX5, TIAM1, TWIST1, TCF15) through differential expression analysis, Unicox and Lasso regression analysis, and then constructed a risk prognosis model. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high-risk and low-risk groups and the different states of the nine prognostic-related EMT-RDGs. The methylation level and mutation status of nine prognostic-related EMT-RDGs all affect their regulation of EMT. The Cox proportional hazards regression model was also constructed by the methylation sites of nine prognostic-related EMT-RDGs. In addition, the expression of FGF8, PHLDB2, SIX2, and SNAIL was higher and the expression level of NOG and TWIST1 was lower in the non-metastasis CRC group. Nine prognostic-related EMT-RDGs also affected the drug treatment response of CRC.

Conclusions

Targeting these nine prognostic-related EMT-RDGs can regulate CRC metastasis and immune, which is beneficial for the prognosis of CRC patients, improve drug sensitivity in CRC patients.
Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages
Authors: Gong Zhitao , Zhan Daqiang , Nie Meng , Li Xiaochun , Gao Chuang , Liu Xuanhui , Xiang Tangtang , Yuan Jiangyuan , Jiang Weiwei , Huang Jinhao , Quan Wei , Wang Dong , Tian Ye , Yuan Hengjie , Zhang Jianning , Jiang Rongcai
Published: September 2021

Background

We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy.

Methods

Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively.

Results

ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA.

Conclusions

We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.
Development of genus-specific universal primers for the detection of flaviviruses
Authors: Daidoji Tomo , Morales Vargas Ronald Enrique , Hagiwara Katsuro , Arai Yasuha , Watanabe Yohei , Nishioka Keisuke , Murakoshi Fumi , Garan Kotaro , Sadakane Hiroki , Nakaya Takaaki
Published: September 2021

Background

Flaviviruses are representative arboviruses carried by arthropods and/or vertebrates; these viruses can pose a public health concern in many countries. By contrast, it is known that a novel virus group called insect-specific flaviviruses (ISFs) also infects arthropods, although no such virus has yet been isolated from vertebrates. The characteristics of ISFs, which affect replication of human-pathogenic flaviviruses within co-infected mosquito cells or mosquitoes without affecting the mosquitoes themselves, mean that we should pay attention to both ISFs and human-pathogenic flaviviruses, despite the fact that ISFs appear not to be directly hazardous to human health. To assess the risk of diseases caused by flaviviruses, and to better understand their ecology, it is necessary to know the extent to which flaviviruses are harbored by arthropods.

Methods

We developed a novel universal primer for use in a PCR-based system to detect a broad range of flaviviruses. We then evaluated its performance. The utility of the novel primer pair was evaluated in a PCR assay using artificially synthesized oligonucleotides derived from a template viral genome sequence. The utility of the primer pair was also examined by reverse transcription PCR (RT-PCR) using cDNA templates prepared from virus-infected cells or crude supernatants prepared from virus-containing mosquito homogenates.

Results

The novel primer pair amplified the flavivirus NS5 sequence (artificially synthesized) in all samples tested (six species of flavivirus that can cause infectious diseases in humans, and flaviviruses harbored by insects). In addition, the novel primer pair detected viral genomes in cDNA templates prepared from mosquito cells infected with live flavivirus under different infectious conditions. Finally, the viral genome was detected with high sensitivity in crude supernatants prepared from pooled mosquito homogenates.

Conclusion

This PCR system based on a novel primer pair makes it possible to detect arthropod-borne flaviviruses worldwide (the primer pair even detected viruses belonging to different genetic subgroups). As such, an assay based on this primer pair may help to improve public health and safety, as well as increase our understanding of flavivirus ecology.
Androgen receptor regulates the proliferation of myoblasts under appropriate or excessive stretch through IGF-1 receptor mediated p38 and ERK1/2 pathways
Authors: Fu Shaoting , Lin Xiaojing , Yin Lijun , Wang Xiaohui
Published: September 2021

Background

Androgen receptor (AR) exerts important roles in exercise-induced alterations of muscle mass, in which the proliferation and differentiation of satellite cells or myoblasts are crucial. Our previous study in C2C12 myoblasts demonstrated that 15% (mimic appropriate exercise) and 20% (mimic excessive exercise) stretches promoted and inhibited the proliferation respectively; and AR played a crucial role in 15% stretch-induced pro-proliferation through IGF-1-modulated PI3K/Akt, p38 and ERK1/2 pathways, but AR’s role in stretches-modulated proliferation of general myoblasts, especially 20% stretch, remains unclear, and the mechanisms need to be further clarified.

Methods

Firstly, the discrepancy in proliferation and the above indicators between L6 (without AR) and C2C12 (with AR) myoblasts were compared under 15% or 20% stretch. Then the influences of transfection AR or exogenous IGF-1 treatment on proliferation and these indicators were detected in stretched L6 myoblasts.

Results

(1) Under un-stretched state, the proliferation of L6 was slower than C2C12 cells. Furthermore, AR knockdown in C2C12 myoblasts repressed, while AR overexpression in L6 myoblasts promoted the proliferation. (2) 15% stretch-induced increases in the proliferation and activities of p38 and ERK1/2 were lower in L6 than C2C12 cells; AR overexpression enhanced the proliferation of 15% stretched L6 cells accompanied with the increases of p38 and ERK1/2 activities. (3) 20% stretch-induced anti-proliferation and inhibition of p38 activity were severer in L6 than C2C12 myoblasts; AR overexpression reversed the anti-proliferation of 20% stretch and enhanced p38 activity in L6 myoblasts. (4) In stretched L6 myoblasts, AR overexpression increased IGF-1R level despite no detectable IGF-1; and recombinant IGF-1 increased the proliferation, the level of IGF-1R, and the activities of p38 and ERK1/2 in 15% stretched L6 myoblasts.

Conclusions

The study demonstrated AR's crucial roles in stretches-regulated proliferation of myoblasts, and increased AR fulfilled 15% stretch's pro-proliferation via activating IGF-1R- p38 and ERK1/2 pathways while decreased AR achieved 20% stretch's anti-proliferation via inhibiting IGF-1R- p38 pathway, which is useful to understand in depth the role and mechanisms of AR in appropriate exercise increasing while excessive exercise decreasing muscle mass.
Analysis of risk factors for perioperative hidden blood loss in unilateral biportal endoscopic spine surgery: a retrospective multicenter study
Authors: Wang Haosheng , Wang Kai , Lv Bin , Li Wenle , Fan Tingting , Zhao Jianwu , Kang Mingyang , Dong Rongpeng , Qu Yang
Published: September 2021

Background

Hidden blood loss (HBL) represents an important complication of unilateral biportal endoscopic (UBE) spine surgery. This study aimed to evaluate HBL and its possible risk factors among patients undergoing UBE surgery for lumbar degenerative diseases.

Methods

This multicentric retrospective study was conducted in 3 different medical centers between July 2020 and April 2021. Data of patients who underwent UBE surgery were extracted by electronic medical record system. The patient’s demographic characteristics and blood loss-related parameters were recorded. We calculated the amount of HBL and explored the association between patient’s characteristics and HBL using Pearson or Spearman correlation analysis. Multivariate linear regression analysis was conducted to identify independent risk factors of HBL.

Results

A total of 136 patients (55 females and 81 males, age range 43 to 74 years) were included in this study. A substantial amount of HBL (469.5 ± 195.3 ml, 57.6% of TBL, total blood loss) occurred following UBE surgery. Multiple linear regression analysis indicated that the risk factors of HBL were as follows: age (P = 0.000), number of fusion levels (P = 0.015), American Society of Anesthesiologists (ASA) classification (P = 0.046), surgery time (P = 0.017), patient’s blood volume (PBV, P = 0.026), total blood loss (TBL, P = 0.001), postoperative (i.e., day 2 or 3) hematocrit (Hct, P = 0.034), Hct loss (P = 0.005), and fibrinogen (P = 0.028).

Conclusions

A certain amount of HBL occurs in UBE surgery and cannot be ignored in daily clinical practice. The age, number of fusion levels, ASA classification, surgery time, PBV, TBL, postoperative Hct, Hct loss, and fibrinogen are independent risk factors for HBL.
Epidemiology, classification, treatment, and mortality of adult femoral neck and basicervical fractures: an observational study of 40,049 fractures from the Swedish Fracture Register
Authors: Sundkvist Jonas , Brüggeman Anders , Sayed-Noor Arkan , Möller Michael , Wolf Olof , Mukka Sebastian
Published: September 2021

Background

Although femoral neck fractures (FNFs) are common in orthopedic departments, optimal treatment methods remain in dispute. There are few large nationwide studies, including basicervical FNFs (bFNFs), on epidemiology, treatment, and mortality. This nationwide study aims to describe the epidemiology, fracture classification, current treatment regimens, and mortality of undisplaced and minimally displaced (Garden I–II, uFNF), displaced (Garden III–IV, dFNF) and bFNFs in adults.

Methods

All FNFs, including bFNFs with a registered injury date between 1 April 2012 and 31 December 2020, were included in this observational study from the Swedish Fracture Register (SFR). Data on age, sex, injury mechanism, fracture classification, primary treatment, and seasonal variation were analyzed.

Results

Some 40,049 FNFs were registered in the SFR. The mean age of the patients in the register was 80.3 (SD 11) years and 63.8% (25,567) were female. Of all FNFs, 25.0% (10,033) were uFNFs, 63.4% (25,383) dFNFs, and 11.6% (4,633) bFNFs. Non-surgical treatment was performed in 0.6% (261) of the patients. Internal fixation (IF) (84.7%) was the main treatment for uFNFs and arthroplasty (87.3%) for dFNFs. For bFNFs, IF (43.8%) and hip arthroplasty (45.9%) were performed equally often. Of the 33,105 patients with a 1-year follow-up mortality at 1-year was 20.6% for uFNF, 24.3% for dFNF, and 25.4% for bFNF.

Conclusion

The main treatment of uFNFs is IF with screws or pins. Hip arthroplasty is the predominant treatment for dFNF. bFNF are more common than previously reported and treated with IF or arthroplasty, depending on patient age. These results may help health care providers, researchers and clinicians better understand the panorama of FNFs in Sweden.

Level of Evidence

IV, retrospective cohort study.
The influence of posterior tibial slope on the mid-term clinical effect of medial-pivot knee prosthesis
Authors: Shi Weipeng , Jiang Yaping , Zhao Xuan , Zhang Haining , Wang Yingzhen , Li Tao
Published: September 2021

Objective

To evaluate the effect of posterior tibial slope (PTS) on the mid-term clinical outcome following a medial-pivot (MP) prosthesis.

Method

Two hundred thirty-three patients from The Affiliated Hospital of Qingdao University, who had undergone a total knee arthroplasty (TKA) with MP prosthesis between January 2015 and December 2015, were retrospectively included in this study. They were divided into 3 groups according to postoperative PTS: A ≤ 5°; B 5-7°; and C ≥ 7°. Multiple assessments were made on the patient postoperatively and recorded in the three groups, the measurements of this study included: the range of motion (ROM), knee scoring system (KSS), Western Ontario and McMaster universities osteoarthritis index (WOMAC), posterior condylar offset (PCO), joint line height, and postoperative complications.

Results

The average post-operative ROM for groups B and C were 108° and 110° respectively; this was significantly higher than that of group A (98°, P < 0.001). The WOMAC scores of patients in group C were significantly lower than those in groups A and B (P < 0.05). However, there were no significant differences in KSS, PCO, and joint line height among the 3 groups (P > 0.05). Only 2 cases of postoperative complications occurred in group C, these were ameliorated after operation.

Conclusion

With an increase to PTS, the postoperative ROM can be significantly increased for the patient. However, the knee joint function will not be significantly improved, and the stability of knee joint will not be affected when within the limits of appropriate PTS.