bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to navigate the application of ethics norms in global health research: reflections based on qualitative research conducted with people with disabilities in Uganda
Authors: Mac-Seing Muriel , Ringuette Louise , Zinszer Kate , Godard Béatrice , Zarowsky Christina 
Published: October 2021

Abstract
Background
As Canadian global health researchers who conducted a qualitative study with adults with and without disabilities in Uganda, we obtained ethics approval from four institutional research ethics boards (two in Canada and two in Uganda). In Canada, research ethics boards and researchers follow the research ethics norms of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS2), and the National Guidelines for Research Involving Humans as Research Participants of Uganda (NGRU) in Uganda. The preparation and implementation of this qualitative research raised specific ethical issues related to research participant privacy and the importance of availability and management of financial resources.

Main body
Our field experience highlights three main issues for reflection. First, we demonstrate that, in a global health research context, methodological and logistic adjustments were necessary throughout the research implementation process to ensure the protection of study participants’ privacy, especially that of people with disabilities, despite having followed the prescribed Canadian and Ugandan ethics norms. Data collection and management plans were adapted iteratively based on local realities. Second, securing financial support as a key aspect of financial management was critical to ensure privacy through disability-sensitive data collection strategies. Without adequate funding, the recruitment of research participants based on disability type, sex, and region or the hiring of local sign language interpreters would not have been possible. Third, although the TCPS2 and NGRU underscore the significance of participants’ privacy, none of these normative documents clearly express this issue in the context of global health research and disability, nor broadly discuss the ethical issue related to financial availability and management.

Conclusions
Conducting research in resource limited settings and with study participants with different needs calls for a nuanced and respectful implementation of research ethics in a global health context. We recommend a greater integration in both the TCPS2 and NGRU of global health research, disability, and responsible conduct of research. This integration should also be accompanied by adequate training which can further guide researchers, be they senior, junior, or students, and funding agencies.
Privacy protection of medical data in social network
Authors: Su Jie , Cao Yi , Chen Yuehui , Liu Yahui , Song Jinming 
Published: October 2021

Abstract
Background
Protection of privacy data published in the health care field is an important research field. The Health Insurance Portability and Accountability Act (HIPAA) in the USA is the current legislation for privacy protection. However, the Institute of Medicine Committee on Health Research and the Privacy of Health Information recently concluded that HIPAA cannot adequately safeguard the privacy, while at the same time researchers cannot use the medical data for effective researches. Therefore, more effective privacy protection methods are urgently needed to ensure the security of released medical data.

Methods
Privacy protection methods based on clustering are the methods and algorithms to ensure that the published data remains useful and protected. In this paper, we first analyzed the importance of the key attributes of medical data in the social network. According to the attribute function and the main objective of privacy protection, the attribute information was divided into three categories. We then proposed an algorithm based on greedy clustering to group the data points according to the attributes and the connective information of the nodes in the published social network. Finally, we analyzed the loss of information during the procedure of clustering, and evaluated the proposed approach with respect to classification accuracy and information loss rates on a medical dataset.

Results
The associated social network of a medical dataset was analyzed for privacy preservation. We evaluated the values of generalization loss and structure loss for different values of k and a, i.e. $$k$$
k
= {3, 6, 9, 12, 15, 18, 21, 24, 27, 30}, a = {0, 0.2, 0.4, 0.6, 0.8, 1}. The experimental results in our proposed approach showed that the generalization loss approached optimal when a = 1 and k = 21, and structure loss approached optimal when a = 0.4 and k = 3.

Conclusion
We showed the importance of the attributes and the structure of the released health data in privacy preservation. Our method achieved better results of privacy preservation in social network by optimizing generalization loss and structure loss. The proposed method to evaluate loss obtained a balance between the data availability and the risk of privacy leakage.
Sustainability of a mobile phone application-based data reporting system in Myanmar’s malaria elimination program: a qualitative study
Authors: Win Han Oo  , Kaung Myat Thu  , Cutts Julia C. , Win Htike  , Kyawt Mon Win  , May Chan Oo  , Galau Naw Hkawng , Agius Paul A. , Pyae Phyo Htoon  , Kearney Ellen , Aung Thi  , Ye Win Aung  , Min Min Thein  , Rosecrans Kathryn , Kyi Tun Lwin  , Aung Kyi Min  , Fowkes Freya J. I. 
Published: October 2021

Abstract
Background
Strengthening surveillance systems to collect near-real-time case-based data plays a fundamental role in achieving malaria elimination in the Greater Mekong Subregion (GMS). With the advanced and widespread use of digital technology, mHealth is increasingly taking a prominent role in malaria surveillance systems in GMS countries, including Myanmar. In Myanmar’s malaria elimination program, an mHealth system called Malaria Case-based Reporting (MCBR) has been applied for case-based reporting of malaria data by integrated community malaria volunteers (ICMVs). However, the sustainability of such mHealth systems in the context of existing malaria elimination programs in Myanmar is unknown.

Methods
Focus group discussions were conducted with ICMVs and semi-structured in-depth interviews were conducted with malaria program stakeholders from Myanmar’s Ministry of Health and Sports and its malaria program implementing partners. Thematic (deductive followed by inductive) analysis was undertaken using a qualitative descriptive approach.

Results
Technological and financial constraints such as inadequate internet access, software errors, and insufficient financial resources to support mobile phone-related costs have hampered users’ access to MCBR. Poor system integrity, unpredictable reporting outcomes, inadequate human resources for system management, and inefficient user support undermined the perceived quality of the system and user satisfaction, and hence its sustainability. Furthermore, multiple parallel systems with functions overlapping those of MCBR were in use.

Conclusions
Despite its effectiveness and efficiency in malaria surveillance, the sustainability of nationwide implementation of MCBR is uncertain. To make it sustainable, stakeholders should deploy a dedicated human workforce with the necessary technical and technological capacities; secure sustainable, long-term funding for implementation of MCBR; find an alternative cost-effective plan for ensuring sustainable system access by ICMVs, such as using volunteer-owned mobile phones for reporting rather than supporting new mobile phones to them; and find a solution to the burden of multiple parallel systems.

Trial registration

Not applicable.
The cost of clinical management of SARS-COV-2 (COVID-19) infection by level of disease severity in Ghana: a protocol-based cost of illness analysis
Authors: Ismaila Hamza , Asamani James Avoka , Lokossou Virgil Kuassi , Oduro-Mensah Ebenezer , Nabyonga-Orem Juliet , Akoriyea Samuel Kaba 
Published: October 2021

Abstract
Background
As the global strategies to fight the SARS-COV-2 infection (COVID-19) evolved, response strategies impacted the magnitude and distribution of health-related expenditures. Although the economic consequence of the COVID-19 pandemic has been dire, and its true scale is yet to be ascertained, one key component of the response is the management of infected persons which its cost has not been adequately examined, especially in Africa.

Methods
To fill gaps in context-specific cost of treating COVID-19 patients, we adopted a health system’s perspective and a bottom-up, point of care resource use data collection approach to estimate the cost of clinical management of COVID-19 infection in Ghana. The analysis was based on the national protocol for management of COVID-19 patients at the time, whether in public or private settings. No patients were enrolled into the study as it was entirely a protocol-based cost of illness analysis.

Result
We found that resource use and average cost of treatment per COVID-19 case varied significantly by disease severity level and treatment setting. The average cost of treating COVID-19 patient in Ghana was estimated to be US$11,925 (GH¢68,929) from the perspective of the health system; ranging from US$282 (GH¢1629) for patients with mild/asymptomatic disease condition managed at home to about US$23,382 (GH¢135,149) for critically ill patients requiring sophisticated and specialised care in hospitals. The cost of treatment increased by some 20 folds once a patient moved from home management to the treatment centre. Overheard costs accounted for 63–71% of institutionalised care compared to only 6% for home-based care. The main cost drivers in overhead category in the institutionalised care were personal protective equipment (PPEs) and transportation, whilst investigations (COVID-19 testing) and staff time for follow-up were the main cost drivers for home-based care.

Conclusion
Cost savings could be made by early detection and effective treatment of COVID-19 cases, preferably at home, before any chance of deterioration to the next worst form of the disease state, thereby freeing up more resources for other aspects of the fight against the pandemic. Policy makers in Ghana should thus make it a top priority to intensify the early detection and case management of COVID-19 infections.
Validity of diagnoses and procedures in Japanese dental claims data
Authors: Ono Sachiko , Ishimaru Miho , Ida Yusuke , Yamana Hayato , Ono Yosuke , Hoshi Kazuto , Yasunaga Hideo 
Published: October 2021

Abstract
Background
Dental claims data have been used for epidemiological studies without establishing the validity of the recorded diagnoses or procedures. The present study aimed to examine the accuracy of diagnoses, procedures, operation time, and the number of teeth recorded in dental claims data.

Methods
We reviewed the charts of 200 patients who visited and 100 patients who were hospitalized in the Department of General Dentistry, Orthodontics, and Oral and Maxillofacial Surgery in an academic hospital between August 2012 and December 2017. The sensitivity and specificity of the dental claims data for five diseases and 15 procedures were evaluated. We assessed the difference in the number of teeth and duration of general anesthesia between claims data and chart reviews.

Results
Sensitivity was more than 86% for six out of seven diagnoses except for pericoronitis (67%). Specificity ranged from 72% (periodontal disease) to 100% (oral cancer for inpatient). The sensitivity of procedures ranged from 10% (scaling for inpatient) to 100%, and the specificity ranged from 6% (food intake on the day of the surgery) to 100%. The mean (standard deviation [SD]) number of teeth in the chart review was 22.6 (6.8), and in the dental claims was 21.6 (8.6). The mean (SD) operation time was 171.2 (120.3) minutes, while the duration of general anesthesia was 270.9 (171.3) minutes.

Conclusions
The present study is the first study to validate dental claims data, and indicates the extent of usefulness of each diagnosis and procedure for future dental research using administrative data.
Frailty and the risk of dementia: is the association explained by shared environmental and genetic factors?
Authors: Bai Ge , Wang Yunzhang , Kuja-Halkola Ralf , Li Xia , Tomata Yasutake , Karlsson Ida K. , Pedersen Nancy L. , Hägg Sara , Jylhävä Juulia 
Published: October 2021

Abstract
Background
Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association.

Methods
The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41–97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment.

Results
A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age.

Conclusions
A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.
Effects of BNT162b2 mRNA vaccine on COVID-19 infection and hospitalisation amongst older people: matched case control study for England
Authors: Mason Thomas F. D. , Whitston Matt , Hodgson Jack , Watkinson Ruth E. , Lau Yiu-Shing , Abdulrazeg Omnia , Sutton Matt 
Published: October 2021

Abstract
Background
The BNT162b2 mRNA vaccine has been shown to be effective at preventing serious COVID-19 events in clinical trials. There is less evidence on effectiveness in real-world settings, especially for older people. Here, we aimed to estimate vaccine effectiveness in the context of the rapid NHS mass-vaccination programme in England, exploiting age-based vaccination eligibility thresholds to minimise and correct for selection bias.

Methods
We studied 170,226 individuals between the ages of 80 and 83 years from community settings outside care homes who received one dose of BNT162b2 mRNA between the 15 and 20 December 2020 and were scheduled a second dose 21 days later. We matched these vaccine recipients to slightly younger (aged 76–79 years) persons not yet eligible to receive the vaccine on gender, area of residence, area deprivation, health status, living arrangements, acute illness, and history of seasonal flu vaccination. We compared their rates of COVID-19 positivity and hospitalisation in the subsequent 45 days. We adjusted for the increasing concentration of COVID-19 positivity in the control population caused by the requirement to have no COVID-19 symptoms prior to vaccination.

Results
Emergency hospital admissions were 51.0% (95% confidence interval 19.9 to 69.5%) lower and positive COVID-19 tests were 55.2% (40.8 to 66.8%) lower for vaccinated individuals compared to matched controls 21 to 27 days after first vaccination. Emergency admissions were 75.6% (52.8 to 87.6%) lower, and positive COVID-19 tests were 70.1% (55.1 to 80.1%) lower 35 to 41 days after first vaccination when 79% of participants had received a second dose within 26 days of their first dose.

Conclusions
Receipt of the BNT162b2 mRNA vaccine is effective at reducing COVID-19 hospitalisations and infections. The nationwide vaccination of older adults in England with the BNT162b2 mRNA vaccine reduced the burden of COVID-19.
Occurrence and molecular characterization of Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi, and Blastocystis sp. in captive wild animals in zoos in Henan, China
Authors: Zhang Kaihui , Zheng Shuangjian , Wang Yilin , Wang Ke , Wang Yuexin , Gazizova Azhar , Han Kelei , Yu Fuchang , Chen Yuancai , Zhang Longxian 
Published: October 2021

Abstract
Background
Captive wild animals in zoos infected with Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi, and Blastocystis sp. can be sources of zoonotic infections and diseases. Therefore, to investigate the distribution of these pathogens in captive wild animals of zoos in Henan, China, a total of 429 fresh fecal samples were collected from six zoos in Henan, China. The infection rates of Cryptosporidium spp., G. duodenalis, E. bieneusi, and Blastocystis sp. were determined by PCR analysis of corresponding loci. Positive results for Cryptosporidium (C. parvum and C. hominis) were subtyped based on the (gp60) gene.

Results
The overall prevalence was 43.1% (185/429), and the prevalence of Cryptosporidium, Giardia duodenalis, Enterocytozoon bieneusi, and Blastocystis sp. were 2.8% (12/429), 0.5% (2/429), 20.8% (89/429), and 19.1% (82/429), respectively. Five Cryptosporidium species, namely, C. hominis, C. parvum, C. muris, C. andersoni, and C. macropodum, were identified in this study. Cryptosporidium parvum was further subtyped as IIdA19G1. Two Giardia duodenalis assemblages (A and E) were also identified. A total of 20 Enterocytozoon bieneusi genotypes were detected, including 18 known (BEB6, D, HND-1, CD7, SDD1, Henan-IV, KIN-1, CHK1, Peru8, Henan-V, CHG11, CHG-1, CHS9, CHG21, Type-IV, CHC9, CM5, and CHB1) and 2 novel genotypes (CHWD1 and CHPM1). A total of nine subtypes of Blastocystis sp. (ST1, ST2, ST3, ST5, ST6, ST7, ST10, ST13, and ST14) were identified in captive wild animals in zoos in the present study. Cryptosporidium andersoni, nine Enterocytozoon bieneusi genotypes, and five Blastocystis subtypes were here first identified in new hosts.

Conclusions
Our study has expanded the host ranges of these four pathogens. The data indicate that animals in zoos can commonly be infected with these four zoonotic pathogens, and animals in zoos are potential sources of zoonotic infections in humans.
A synergistic effect of variability in estimated glomerular filtration rate with chronic kidney disease on all-cause mortality prediction in patients with type 2 diabetes: a retrospective cohort study
Authors: Chang Yu-Shan , Li Yu-Hsuan , Lee I-Te 
Published: October 2021

Abstract
Background
The combination of diabetes mellitus (DM) and chronic kidney disease (CKD) is associated with a high risk of mortality. Annual assessment of the estimated glomerular filtration rate (eGFR) is recommended for patients with DM. We investigated the effect of variability in annual eGFR values on all-cause mortality in patients with type 2 DM.

Methods
In this retrospective cohort study, we enrolled patients with eGFR data between 01 Aug 2017 and 31 July 2018. We defined the index eGFR as the first available eGFR value within the enrollment year and collected additional annual eGFR data from the previous three years. A total of 3592 patients with type 2 DM were enrolled, including 959 patients with CKD (index eGFR < 60 mL/min/1.73 m2) and 2633 patients without CKD. We assessed eGFR variability by using the standard deviation (SD) of the three annual eGFR and index eGFR values. We divided patients into subgroups according to the median SD of their annual eGFR (7.62 mL/min/1.73 m2). The primary endpoint was all-cause mortality after the index eGFR was assessed.

Results
During a median follow-up of 19 months (interquartile range: 18‒20 months), 127 (3.5%) deaths occurred among all 3592 enrolled patients. The highest mortality risk was observed in the high SD with CKD group, with a hazard ratio (HR) of 2.382 [95% confidence interval (CI) 1.346‒4.215] in comparison to the low SD without CKD group after adjusting for the associated factors. In patients without CKD, a high SD was an independent risk factor for mortality (HR = 2.105, 95% CI 1.256‒3.528). According to the C-index, the mortality prediction ability was better for the index eGFR + SD model than for the index eGFR alone model (0.671 vs. 0.629, P < 0.001).

Conclusion
There was a synergistic effect of eGFR variability with single-measured eGFR for the prediction of mortality in patients with type 2 DM. The SD of the annual eGFR values was also an independent predictor of mortality in patients with an eGFR > 60 mL/min/1.73 m2.
Production of soluble regulatory hydrogenase from Ralstonia eutropha in Escherichia coli using a fed-batch-based autoinduction system
Authors: Fan Qin , Neubauer Peter , Gimpel Matthias 
Published: October 2021

Abstract
Background
Autoinduction systems can regulate protein production in Escherichia coli without the need to monitor cell growth or add inducer at the proper time following culture growth. Compared to classical IPTG induction, autoinduction provides a simple and fast way to obtain high protein yields. In the present study, we report on the optimization process for the enhanced heterologous production of the Ralstonia eutropha regulatory hydrogenase (RH) in E. coli using autoinduction. These autoinduction methods were combined with the EnPresso B fed-batch like growth system, which applies slow in situ enzymatic glucose release from a polymer to control cell growth and protein synthesis rate.

Results
We were able to produce 125 mg L−1 RH corresponding to a productivity averaged over the whole process time of 3 mg (L h)−1 in shake flasks using classic single-shot IPTG induction. IPTG autoinduction resulted in a comparable volumetric RH yield of 112 mg L−1 and due to the shorter overall process time in a 1.6-fold higher productivity of 5 mg (L h)−1. In contrast, lactose autoinduction increased the volumetric yield more than 2.5-fold and the space time yield fourfold reaching 280 mg L−1 and 11.5 mg (L h)−1, respectively. Furthermore, repeated addition of booster increased RH production to 370 mg L−1, which to our knowledge is the highest RH concentration produced in E. coli to date.

Conclusions
The findings of this study confirm the general feasibility of the developed fed-batch based autoinduction system and provide an alternative to conventional induction systems for efficient recombinant protein production. We believe that the fed-batch based autoinduction system developed herein will favor the heterologous production of larger quantities of difficult-to-express complex enzymes to enable economical production of these kinds of proteins.