bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the key performance indicators for digital health interventions: A scoping review
Authors: Brenner Maria , Weir Arielle , McCann Margaret , Doyle Carmel , Hughes Mary , Moen Anne , Ingvar Martin , Nauwelaerts Koen , Turk Eva , McCabe Catherine 
Published: January 2023

Background Digital health interventions offer new methods for delivering healthcare, with the potential to innovate healthcare services. Key performance indicators play a role in the evaluation, measurement, and improvement in healthcare quality and service performance. The aim of this scoping review was to identify current knowledge and evidence surrounding the development of key performance indicators for digital health interventions. Methods A literature search was conducted across ten key databases: AMED – The Allied and Complementary Medicine Database, CINAHL – Complete, Health Source: Nursing/Academic Edition, MEDLINE, APA PsycINFO, EMBASE, EBM Reviews – Cochrane Database of Systematic Reviews, EBM Reviews – Database of Abstracts of Reviews of Effects, EBM Reviews – Health Technology Assessment, and IEEE Xplore. Results Five references were eligible for the review. Two were articles on original research studies of a specific digital health intervention, and two were overviews of methods for developing digital health interventions (not specific to a single digital health intervention). All the included reports discussed the involvement of stakeholders in developing key performance indicators for digital health interventions. The step of identifying and defining the key performance indicators was completed using various methodologies, but all centred on a form of stakeholder involvement. Potential options for stakeholder involvement for key performance indicator identification include the use of an elicitation framework, a factorial survey approach, or a Delphi study. Conclusions Few articles were identified, highlighting a significant gap in evidence-based knowledge in this domain. All the included articles discussed the involvement of stakeholders in developing key performance indicators for digital health interventions, which were performed using various methodologies. The articles acknowledged a lack of literature related to key performance indicator development for digital health interventions. To allow comparability between key performance indicator initiatives and facilitate work in the field, further research would be beneficial to develop a common methodology for key performance indicators development for digital health interventions.
Isolation and characterization of apical papilla cells from root end of human third molar and their differentiation into cementoblast cells: an in vitro study
Authors: Ebadi Morvarid , Miresmaeili Amirfarhang , Rajabi Sarah , Shojaei Shahrokh , Farhadi Sareh 
Published: January 2023

AbstractBackgroundPeriodontal regeneration, treatment of periodontal-related diseases and improving the function of implants are global therapeutic challenges. The differentiation of human stem cells from apical papilla into cementoblasts may provide a strategy for periodontitis treatment. This study aimed to evaluate the differentiation of primary human stem cells apical papilla (hSCAPs) to cementoblast cells.Material and methodsSCAPs cells were isolated from human third molar and then incubated for 21 days in a differentiation microenvironment. Alkaline phosphatase (ALP) and Alizarin red S staining assays were performed to evaluate the calcium deposition and formation of hydroxyapatite in the cultured hSCAPs microenvironment. Real-time polymerase chain reaction (RT-PCR) assay was performed for cementum protein 1 (CEMP1), collagen type I (COL1), F-Spondin (SPON1), osteocalcin (OCN), and osteopontin (OPN) as specific markers of cementoblasts and their progenitors.ResultsALP phosphatase activity in day 21 of treatment demonstrated a significant increase in ALP compared to the control. Alizarin red S staining assay showed that the differentiated hSCAPs offered a great amount of calcium deposition nodules compared to the control. The increased expression level of CEMP1, OCN, OPN, COL1 and Spon1 was observed in days 7, 14 and 21 compared to the control, while greatest expression level was observed in day 21.ConclusionIn conclusion, the differentiation microenviroment is convenient and useful for promoting the differentiation of hSCAPs into cementoblast.
Comparative and expression analyses of AP2/ERF genes reveal copy number expansion and potential functions of ERF genes in Solanaceae
Authors: Choi Jin-Wook , Choi Hyeon Ho , Park Young-Soo , Jang Min-Jeong , Kim Seungill 
Published: January 2023

AbstractBackgroundThe AP2/ERF gene family is a superfamily of transcription factors that are important in the response of plants to abiotic stress and development. However, comprehensive research of the AP2/ERF genes in the Solanaceae family is lacking.ResultsHere, we updated the annotation of AP2/ERF genes in the genomes of eight Solanaceae species, as well asArabidopsis thalianaandOryza sativa.We identified 2,195 AP2/ERF genes, of which 368 (17%) were newly identified. Based on phylogenetic analyses, we observed expansion of the copy number of these genes, especially those belonging to specific Ethylene-Responsive Factor (ERF) subgroups of the Solanaceae. From the results of chromosomal location and synteny analyses, we identified that the AP2/ERF genes of the pepper (Capsicum annuum), the tomato (Solanum lycopersicum), and the potato (Solanum tuberosum) belonging to ERF subgroups form a tandem array and most of them are species-specific without orthologs in other species, which has led to differentiation of AP2/ERF gene repertory among Solanaceae. We suggest that these genes mainly emerged through recent gene duplication after the divergence of these species. Transcriptome analyses showed that the genes have a putative function in the response of the pepper and tomato to abiotic stress, especially those in ERF subgroups.ConclusionsOur findings will provide comprehensive information on AP2/ERF genes and insights into the structural, evolutionary, and functional understanding of the role of these genes in the Solanaceae.
Prevention and screening during the COVID-19 pandemic: qualitative findings from the BETTER WISE project
Authors: Sopcak N. , Wong M. , Fernandes C. , Ofosu D. , Khalil I. , Manca D. 
Published: January 2023

Abstract
Background
The COVID-19 pandemic challenged healthcare systems worldwide and disrupted primary care, particularly prevention, screening, and lifestyle counselling. BETTER WISE is a comprehensive and structured approach that proactively addresses cancer and chronic disease prevention and screening (CCDPS), including cancer survivorship and screening for poverty and lifestyle risks for patients aged 40 to 65. Patients from 13 primary care clinics (urban, rural, and remote) in Alberta, Ontario, and Newfoundland & Labrador, Canada were invited for a 1-hour visit with a prevention practitioner (PP), a member of the primary care team with specialized training in CCDPS to provide patients an overview of eligible screening and assist with lifestyle counselling. This qualitative sub-study describes how the COVID-19 pandemic impacted BETTER WISE in a constantly changing medical landscape.

Methods
We conducted 17 focus groups and 48 key informant interviews with a total of 132 primary care providers (PPs, physicians, allied health professionals, and clinic staff) over three different time points to better understand their perspectives on the BETTER WISE project. We also received 585 patient feedback forms of the 1005 patients who agreed to participate in the study. We also collected field notes and memos and employed thematic analysis using a constant comparative method focused on the impact of the pandemic on BETTER WISE.

Results
We identified four themes related to how the COVID-19 pandemic impacted the BETTER WISE study: 1) Switch of in-person visits to visits over the phone; 2) Lack of access to preventive care and delays of screening tests; 3) Changes in primary care providers’ availability and priorities; 4) Mental health impacts of the pandemic on patients and primary care providers.

Conclusions
The COVID-19 pandemic had and, at the time of writing, continues to have an impact on primary care, particularly on prevention, screening, and lifestyle counselling. Despite structural, procedural, and personal challenges throughout different waves of the pandemic, the primary care clinics participating in BETTER WISE were able to complete the study. Our results underscore the importance of the role of primary care providers in adapting to changing circumstances and support of patients in these challenging times.

Trial registration
This qualitative study is a sub-component of the BETTER WISE pragmatic, cRCT, trial registration ISRCTN21333761 (date of registration 19/12/2016).
Association between long COVID, functional activity, and health-related quality of life in older adults
Authors: Shanbehzadeh Sanaz , Zanjari Nasibeh , Yassin Marzieh , Yassin Zeynab , Tavahomi Mahnaz 
Published: January 2023

Abstract
Background
Older adults experience persistent symptoms post-COVID-19, termed as Long COVID, affecting their physical and mental health. This study aimed to evaluate the effects of Long COVID, level of physical activity, and functional decline on older adults’ health-related quality of life post-COVID-19.

Methods
This cross-sectional study was conducted on 121 older adults with 60 to 90 years old post-coronavirus infection. The standardized metrics used in the study were Fatigue Severity Scale, Physical Activity Elderly, SF12, Post-COVID-19 functional status scale, and COVID-19 Yorkshire rehabilitation screening scale. The severity of coronavirus infection was evaluated by changes in chest CT scan images and O2 saturation at hospital admission. Data were analyzed using linear regression analyses.

Results
The results of regression analysis revealed six factors to be predictors of physical health at 6 months post-COVID-19 (F = 9.046, P < 0.001; explained variance 63%), which the significant factors were fatigue, level of physical activity, worsened pain, difficulties in activities of daily living and cognitive-communication problems. Among these factors, greater fatigue and worsened pain intensity were the strongest predictors. Mental health was associated with days of hospitalization and cognitive-communication problems (F = 2.866, P < 0.001; explained variance 35%).

Conclusions
Considering the negative impact of fatigue, pain, low physical activity, and cognitive-communication problems on health-related quality of life, early and accurate evaluation and management are required for recovered older adults post-COVID-19.
Association between red blood cell folate and Trichomonas vaginalis infection among women
Authors: Liao Wan-Zhe , Zhou Zhi-Yi , Mao Jun-Hao , Wang Zi-Xun , Hu Yi-Ming , Lou Yong-Fu , Zheng Qiao-Rui , Guo Xu-Guang 
Published: January 2023

Abstract
Background
Increased folic acid has been found to be latently protective against gynecological infection, including several kinds of vaginosis. In this study, we laid emphasis on whether RBC (Red Blood Cell) folate was associated with the infectious ratio of Trichomonas vaginalis, a kind of anaerobic parasitic protozoan.

Methods
We set RBC folate as the exposure variable and Trichomonas vaginalis as the outcome variable. Other subsidiary variables were regarded as covariates that may work as potential effect modifiers. The cross-sectional study was conducted with two merged waves of the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004, and a sample of 1274 eligible women (1212 negative and 62 positive in Trichomonas vaginalis infection) was integrated for the exploration of the association between RBC folate and Trichomonas vaginalis infection. Multivariate regression analyses, subgroup analyses, and subsequent smooth curve fittings were conducted to estimate the relationship between RBC folate and Trichomonas vaginalis in women.

Results
In the multivariable logistic regression analyses, a negative association was observed between stratified RBC folate status and Trichomonas vaginalis infection with all confounders adjusted. Referencing the lowest RBC folate concentration quartile, the higher concentration quartiles reported a relatively lower infection ratio, while there was a weak correlation between total RBC folate concentration and T. vaginalis (Trichomonas vaginalis) infection. In subgroup analyses stratified by BMI and age, this association was only found significant in high age and BMI groups.

Conclusions
The cross-sectional study indicated a negative association between RBC folic acid and Trichomonas vaginalis infection, and latent effects of BMI and age on the association were also found.
Major risk factors for Streptococcus dysgalactiae subsp. equisimilis bacteremia: a population-based study
Authors: Nevanlinna Viivi , Huttunen Reetta , Aittoniemi Janne , Luukkaala Tiina , Rantala Sari 
Published: January 2023

Abstract
Background
Streptococcus dysgalactiae subspecies equisimilis is a human pathogen causing severe invasive infections. Detailed information on S. dysgalactiae subsp. equisimilis bacteremia and especially of predisposing factors are lacking. The purpose of the study is to investigate the risk factors of S. dysgalactiae subsp. equisimilis bacteremia compared to the general population in Finland.

Methods
We retrospectively reviewed all patients older than 18 years with S. dysgalactiae subsp. equisimilis bacteremia in the Pirkanmaa health district from August 2015 to July 2018. The risk factors for S. dysgalactiae subsp. equisimilis bacteremia were investigated with respect to the normal population in Finland using the Finhealth study data provided by the Finnish institute for health and welfare. The study group was matched with the Finhealth study by age and sex.

Results
Altogether 230 cases of S. dysgalactiae subsp. equisimilis bacteremia were detected. The medical records of 217 episodes of S. dysgalactiae subsp. equisimilis bacteremia (involving 211 patients) were available for analysis. Obesity was a statistically significant risk factor for S. dysgalactiae subsp. equisimilis bacteremia (Odds Ratio 2.96 [95% CI 2.22–3.96]). Diabetes and coronary artery disease were also associated with an increased risk of S. dysgalactiae subsp. equisimilis bacteremia (OR 4.82 [95% CI 3.62–6.42]) and (OR 3.03 [95% CI 2.18–4.19]).

Conclusions
We found obesity, diabetes, and coronary artery disease to be associated with an increased risk for S. dysgalactiae subsp. equisimilis bacteremia. These results provide an increased understanding of risk factors for S. dysgalactiae subsp. equisimilis bacteremia.
Impact of an external ventricular shunt (EVD) handling protocol on secondary meningitis rates: a historical cohort study with propensity score matching
Authors: Hoefnagel Daphna , Volovici Victor , dos Santos Rubio Ellianne J. , Voor in’t Holt Anne F. , Dirven Clemens M. F. , Vos Margreet C. , Dammers Ruben 
Published: January 2023

Abstract
Background
External ventricular drainage (EVD) is frequently used in neurosurgical procedures for cerebrospinal fluid (CSF) drainage. It is, however, associated with high infection rates, namely secondary meningitis and ventriculitis. Based on a previous high prevalence of these infections among patients with EVDs, we have proposed and implemented a protocol in an effort to decrease the infection rate. The aim of this study was to measure the effect of hospital-wide implementation of the EVD handling protocol on secondary EVD infections.

Patients and methods
We included 409 consecutive patients who received a new EVD for other indications than infectious pathologies from January 2000 until June 2012. Patients above 18 years of age were divided into pre- (n = 228) and post-protocol (n = 181) groups. Patient and disease demographics, as well as EVD data together with confounders for secondary meningitis were recorded in a database. Propensity score matching was then performed to create groups matched for sex, age, reason for drainage, type of shunt, time in situ and duration of surgery to place the EVD. Binomial logistic regression for confounder adjustment and regression discontinuity analyses were then performed on the matched cohort.

Results
Infections occurred more frequently in the pre-protocol group (23% vs 9%, p <  0.001). The incidence of infection was 33/1000 drain-days pre-protocol and 9/1000 drain-days post-protocol. Regression analysis in a propensity score-matched cohort (n = 103 in the pre- and n = 178 in the post-protocol groups) showed that the pre-protocol period was independently associated with more infections (OR 2.69; 95%-CI 1.22–5.95, p = 0.01).

Conclusions
The incidence of secondary EVD infections can be reduced significantly by the implementation of a strict hospital-wide EVD handling protocol.
Anti-cancer effect of afatinib, dual inhibitor of HER2 and EGFR, on novel mutation HER2 E401G in models of patient-derived cancer
Authors: Harada Yohei , Sato Akemi , Nakamura Hideaki , Kai Keita , Kitamura Sho , Nakamura Tomomi , Kurihara Yuki , Ikeda Sadakatsu , Sueoka Eisaburo , Kimura Shinya , Sueoka-Aragane Naoko 
Published: January 2023

Abstract
Background
Precision medicine with gene panel testing based on next-generation sequencing for patients with cancer is being used increasingly in clinical practice. HER2, which encodes the human epidermal growth factor receptor 2 (HER2), is a potentially important driver gene. However, therapeutic strategies aimed at mutations in the HER2 extracellular domain have not been clarified. We therefore investigated the effect of EGFR co-targeted therapy with HER2 on patient-derived cancer models with the HER2 extracellular domain mutation E401G, based on our previous findings that this mutation has an epidermal growth factor receptor (EGFR)-mediated activation mechanism.

Methods
We generated a xenograft (PDX) and a cancer tissue-originated spheroid (CTOS) from a patient’s cancer containing an amplified HER2 E401G mutation. With these platforms, we compared the efficacy of afatinib, a tyrosine kinase inhibitor having anti-HER2 and anti-EGFR activity, with two other therapeutic options: lapatinib, which has similar properties but weaker EGFR inhibition, and trastuzumab plus pertuzumab, for which evidence exists of treatment efficacy against cancers with wild-type HER2 amplification. Similar experiments were also performed with H2170, a cell line with wild-type HER2 amplification, to contrast the characteristics of these drug’s efficacies against HER2 E401G.

Results
We confirmed that PDX and CTOS retained morphological and immunohistochemical characteristics and HER2 gene profiles of the original tumor. In both PDX and CTOS, afatinib reduced tumor size more than lapatinib or trastuzumab plus pertuzumab. In addition, afatinib treatment resulted in a statistically significant reduction in HER2 copy number at the end of treatment. On the other hand, in H2170 xenografts with wild-type HER2 amplification, trastuzumab plus pertuzumab was most effective.

Conclusions
Afatinib, a dual inhibitor of HER2 and EGFR, showed a promising effect on cancers with amplified HER2 E401G, which have an EGFR-mediated activation mechanism. Analysis of the activation mechanisms of mutations and development of therapeutic strategies based on those mechanisms are critical in precision medicine for cancer patients.
Are we facing an increasing surgical demand for high myopic traction maculopathies? A 12-year study from Hong Kong
Authors: Li Kenneth K. W. , Wong Daniel H. T. , Li Patrick S. H. 
Published: January 2023

Abstract
Purpose
We aimed to investigate the longitudinal change in the number of surgically operated myopic traction maculopathies (MTM) cases at a tertiary eye centre.

Methods
A retrospective study of all consecutive cases of surgically operated MTM over 12 years (2009-2020) was conducted in a myopia prevalent region. We compared outcomes among three groups: (1) myopic macular hole (MH), (2) myopic macular hole with retinal detachment (MHRD), and (3) myopic foveoschisis with retinal detachment (MFRD).

Results
Fifty-one cases were included in the study (8 cases of MH, 33 cases of MHRD and 10 cases of MFRD). The overall mean age was 63.8 +/- 8.7 with a female preponderance (2:1). The mean age of the MH group (58.6) was significantly younger than the MHRD group (64.2) and MFRD group (66.6) (p = 0.02). Subgroup analysis using ATN classification did not show its correlation with both visual improvement and anatomical success. When comparing the first 6-year period (2009-2014) with the second 6-year period (2015-2020), there was a significant increase in the number of cases (p = 0.01).

Conclusion
We observe an increase in the number of surgically operated MTM. This follows the trend of the global rise in the prevalence of myopia and baby boomers entering retirement.
A nomogram model for predicting ocular GVHD following allo-HSCT based on risk factors
Authors: Wang Wen-hui , You Li-li , Huang Ke-zhi , Li Zi-jing , Hu Yu-xin , Gu Si-min , Li Yi-qing , Xiao Jian-hui 
Published: January 2023

Abstract
Objective
To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT).

Methods
This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis.

Results
Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895–1.000) and 0.969
(95% CI, 0.846–1.000), respectively.And the Hosmer–Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691).

Conclusion
We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.