bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyze the usage of urban greenways through social media images and computer vision
Authors: Song Yang , Ning Huan , Ye Xinyue , Chandana Divya , Wang Shaohua
Published: January 2022

Urban greenway is an emerging form of urban landscape offering multifaceted benefits to public health, economy, and ecology. However, the usage and user experiences of greenways are often challenging to measure because it is costly to survey such large areas. Based on the online postings from Instagram in 2017, this paper used Computer Vision (CV) technology to analyze and compare how the general public uses two typical greenway parks, The High Line in New York City and the Atlanta Beltline in Atlanta. Face and object detection analysis were conducted to infer user composition, activities, and key experiences. We presented the temporal patterns of Instagram postings as well as the group gatherings, smiling, and representative objects detected from photos. Our results have shown high user engagement levels for both parks while teens are significantly underrepresented. The High Line had more group activities and was more active during weekdays than the Atlanta Beltline. Stronger sense of escape and physical activities can be found in Atlanta Beltline. In summary, social media images like Instagram can provide strong empirical evidence for urban greenway usage when combined with artificial intelligence technologies, which can support the future practice of landscape architecture and urban design.
Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions
Authors: Koltai Tomas , Fliegel Larry
Published: January 2022

The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers. The 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin is functionally the most active of these compounds. This group of flavonoids has been extensively studied and they have been used as hepato-protective substances for the mushroom Amanita phalloides intoxication and mainly chronic liver diseases such as alcoholic cirrhosis and nonalcoholic fatty liver. Hepatitis C progression is not, or slightly, modified by silymarin. Recently, it has also been proposed for SARS COVID-19 infection therapy. The biochemical and molecular mechanisms of action of these substances in cancer are subjects of ongoing research. Paradoxically, many of its identified actions such as antioxidant, promoter of ribosomal synthesis, and mitochondrial membrane stabilization, may seem protumoral at first sight, however, silymarin compounds have clear anticancer effects. Some of them are: decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others. Interestingly, the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected. Furthermore, there is a long history of silymarin use in human diseases without toxicity after prolonged administration. The ample distribution and easy accessibility to milk thistle—the source of silymarin compounds, its over the counter availability, the fact that it is a weed, some controversial issues regarding bioavailability, and being a nutraceutical rather than a drug, has somehow led medical professionals to view its anticancer effects with skepticism. This is a fundamental reason why it never achieved bedside status in cancer treatment. However, in spite of all the antitumoral effects, silymarin actually has dual effects and in some cases such as pancreatic cancer it can promote stemness. This review deals with recent investigations to elucidate the molecular actions of this flavonoid in cancer, and to consider the possibility of repurposing it. Particular attention is dedicated to silymarin's dual role in cancer and to some controversies of its real effectiveness.
Multiphasic screening of priority chemical compounds in drinking water by process control and human health risk
Authors: Liu Yan , Li Xue , Qiao Xiaocui , Zhao Xingru , Ge Simin , Wang Haiyan , Li Dan
Published: January 2022

Background

The residual chemical pollutants in drinking water may cause adverse effects on human health. Chemical compounds potentially affecting human health have been widely explored, while the multiphasic evaluation of chemical compounds by process control and human health risk is still rarely reported. In the present study, we used multiphasic criteria to assess the health risk including effluent concentration, accumulation index, purification index for the removal efficiency during the drinking water treatment processes, carcinogen classification based on the International Agency for Research on Cancer standards, non-carcinogenic health hazards and carcinogenic risk.

Results

Among the monitored chemicals, 47 and 44 chemical compounds were detected in raw water and treated water, respectively. The generation and removal of chemical compounds implied that the migration and transformation of chemicals during the purification processes affected the effluent concentration, posing a direct potential health risk. Of these compounds, 41 contaminants’ profiles were screened as priority chemical compounds (PCCs).

Conclusions

The top eight PCCs with high carcinogenic risk were highlighted. Some effective steps, such as protecting the raw water sources, improving the removal performance and reducing the disinfection by-products during the purification process by introducing advanced treatment technologies, were suggested to maintain drinking water security. Collectively, our findings provided novel scientific supports for the sustainable management of drinking water to promote human health.

Graphical Abstract
Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats
Authors: Wang Chenran , Sun Shen , Jiao Jing , Yu Xinhua , Huang Shaoqiang
Published: January 2022

Background

Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics.

Methods

Anesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg−1·min−1 normal saline, group LE received 2 ml·kg−1·min−1 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg−1·min−1 until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated.

Results

All three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4–20.7] versus 7.2 [5.9–8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0–29.1] versus 11.3 [10.7–13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9–11.7] versus 5.6 [4.5–7.0], p = 0.060).

Conclusions

Our data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.
Usefulness of estimated pulse wave velocity for identifying prevalent coronary heart disease: findings from a general Chinese population
Authors: He Xiao-Wu , Park Jieun , Huang Wen-Sheng , Leng Li-Hua , Yu Yan , Pei Yi-Bin , Zhu Gao , Wu Shaohui
Published: January 2022

Background

Aortic stiffness and coronary heart disease (CHD) share a similar spectrum of risk factors; previous studies have identified the association between aortic stiffness and CHD. Recent studies have demonstrated estimated pulse wave velocity (ePWV) as a simple and easy-acquired indicator of aortic stiffness. Our work aims to evaluate the association between ePWV and the prevalence of CHD and assess the value of ePWV for the identification of prevalent CHD.

Methods

The current cross-sectional work included 7012 subjects from rural areas of southeastern China between September 2020 and February 2021. ePWV was calculated from age and mean blood pressure by specific algorithm.

Results

The prevalence of CHD in our population was 3.58% (251 patients among 7012 subjects). After adjusting for age, sex, education, income and exercise level, current smoking and drinking status, body mass index, waist circumference, fasting plasma glucose, total cholesterol, high density lipoprotein, estimated glomerular filtration rate and cerebrovascular diseases, each standard deviation increment of ePWV would produce an additional 37.8% risk of prevalent CHD. Moreover, after dividing ePWV into quartiles, the 4th quartile of ePWV showed a significant risk of prevalent CHD (OR (95% CI): 3.567 (1.963–6.479)) when compared with the 1st quartile. Additionally, the subgroup analysis showed the association between ePWV and prevalent CHD was robust to several common risk factors of CHD, including age, sex, body mass index, hypertension, diabetes and reduced estimated glomerular filtration rate. Finally, the area under curve (AUC) displayed an improvement when adding ePWV into common CHD risk factors (0.705 vs. 0.718. P = 0.044). Consistently, net reclassification index (0.436, 95% CI: 0.301–0.571, P < 0.001) and integrated discrimination index (0.004, 95% CI: 0.001–0.006, P = 0.002) demonstrated the value of ePWV to optimize the identification of prevalent CHD in the general population.

Conclusion

The present analysis implicates the robust association between ePWV, a simple, rapid, and practical marker of aortic stiffness, and prevalent CHD in the general Chinese population. More importantly, the results suggest the value of ePWV as a potential marker to improve the identification of prevalent CHD.
K-means for shared frailty models
Authors: Govindarajulu Usha , Bedi Sandeep
Published: January 2022

Background

The purpose of this research was to see how the k-means algorithm can be applied to survival analysis with single events per subject for defining groups, which can then be modeled in a shared frailty model to further allow the capturing the unmeasured confounding not already explained by the covariates in the model.

Methods

For this purpose we developed our own k-means survival grouping algorithm to handle this approach. We compared a regular shared frailty model with a regular grouping variable and a shared frailty model with a k-means grouping variable in simulations as well as analysis on a real dataset.

Results

We found that in both simulations as well as real data showed that our k-means clustering is no different than the typical frailty clustering even under different situations of varied case rates and censoring. It appeared our k-means algorithm could be a trustworthy mechanism of creating groups from data when no grouping term exists for including in a frailty term in a survival model or comparing to an existing grouping variable available in the current data to use in a frailty model.
Ipsilesional volume loss of basal ganglia and thalamus is associated with poor hand function after ischemic perinatal stroke
Authors: Ilves Nigul , Lõo Silva , Ilves Norman , Laugesaar Rael , Loorits Dagmar , Kool Pille , Talvik Tiina , Ilves Pilvi
Published: January 2022

Background

Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early MRI is not available in patients with delayed presentation of PS and prediction of hemiparesis severity remains a challenge.

Aims

To evaluate the volumes of the basal ganglia, amygdala, thalamus, and hippocampus following perinatal ischemic stroke in relation to hand motor function in children with a history of PS and to compare the volumes of subcortical structures in children with PS and in healthy controls.

Methods

Term born PS children with arterial ischemic stroke (AIS) (n = 16) and with periventricular venous infarction (PVI) (n = 18) were recruited from the Estonian Pediatric Stroke Database. MRI was accuired during childhood (4-18 years) and the volumes of the basal ganglia, thalamus, amygdala and hippocampus were calculated. The results of stroke patients were compared to the results of 42 age- and sex-matched healthy controls. Affected hand function was evaluated by Assisting Hand Assessment (AHA) and classified by the Manual Ability Classification System (MACS).

Results

Compared to the control group, children with AIS had smaller volumes of the ipsi- and contralesional thalami, ipsilesional globus pallidus, nucleus accumbens and hippocampus (p < 0.005). Affected hand function in children with AIS was correlated with smaller ipsilesional thalamus, putamen, globus pallidus, hippocampus, amygdala and contralesional amygdala (r > 0.5;p < 0.05) and larger volume of the contralesional putamen and hippocampus (r < − 0.5;p < 0.05).

In children with PVI, size of the ipsilesional caudate nucleus, globus pallidus, thalamus (p ≤ 0.001) and hippocampus (p < 0.03) was smaller compared to controls. Smaller volume of the ipsi- and contralesional thalami and ipsilesional caudate nucleus was correlated with affected hand function (r > 0.55;p < 0.05) in children with PVI.

Conclusions

Smaller volume of ipsilesional thalamus was associated with poor affected hand function regardless of the perinatal stroke subtype. The pattern of correlation between hand function and volume differences in the other subcortical structures varied between children with PVI and AIS. Evaluation of subcortical structures is important in predicting motor outcome following perinatal stroke.
Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study
Authors: Tian Zhichao , Dong Shuping , Yang Yang , Gao Shilei , Yang Yonghao , Yang Jinpo , Zhang Peng , Wang Xin , Yao Weitao
Published: January 2022

Background

There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited.

Methods

The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan–Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant.

Results

A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8–3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018).

Conclusion

Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.
Ocular phenotype and genetical analysis in patients with retinopathy of prematurity
Authors: Tao Tianchang , Meng Xianfen , Xu Ningda , Li Jiarui , Cheng Yong , Chen Yi , Huang Lvzhen
Published: January 2022

Background

Retinopathy of prematurity (ROP) is a multifactorial retinal disease, involving both environmental and genetic factors; The purpose of this study is to evaluate the clinical presentations and genetic variants in Chinese patients with ROP.

Methods

A total of 36 patients diagnosed with ROP were enrolled in this study, their medical and ophthalmic histories were obtained, and comprehensive clinical examinations were performed. Genomic DNA was isolated from peripheral blood of ROP patients, polymerase chain reaction and direct sequencing of the associated pathogenic genes (FZD4, TSPAN12, and NDP) were performed.

Results

All patients exhibited the clinical manifestations of ROP. No mutations were detected in the TSPAN12 and NDP genes in all patients; Interestingly, three novel missense mutations were identified in the FZD4 gene (p.A2P, p.L79M, and p.Y378C) in four patients, for a detection rate of 11.1% (4/36).

Conclusions

This study expands the genotypic spectrum of FZD4 gene in ROP patients, and our findings underscore the importance of obtaining molecular analyses and comprehensive health screening for this retinal disease.
Psychosocial and mental health challenges faced by emerging adults living with HIV and support systems aiding their positive coping: a qualitative study from the Kenyan coast
Authors: Nyongesa Moses K. , Nasambu Carophine , Mapenzi Rachael , Koot Hans M. , Cuijpers Pim , Newton Charles R. J. C. , Abubakar Amina
Published: January 2022

Background

In sub-Saharan Africa, there is little data on the challenges faced by young people living with HIV transitioning into adult life. Adapting the socio-ecological framework, this qualitative study investigated the challenges faced by emerging adults living with HIV from a rural Kenyan setting. Additionally, the study explored support systems that aid positive coping among these young adults.

Methods

In April 2018, in-depth interviews were conducted with a convenience sample of 22 young adults living with HIV (12 females), 18–24 years old, from rural Kilifi, coast of Kenya. Data were analyzed thematically using NVIVO 11 software.

Results

Young adults living with HIV from this setting face various challenges at different levels of the social ecosystem. At the individual level, key challenges they reported included acceptance of HIV positive status, antiretroviral adherence, economic burden associated with access to healthcare, building an intimate relationship, mental health problems, and HIV status disclosure. At the family level, death of parents, poverty, and being unaccepted were the commonly mentioned challenges. At the community level, socialization difficulties and long waiting time at the HIV clinic were highlighted. HIV stigma and discrimination were frequently reported across the different levels. Economic independence, social support (from families, friends, organizations, healthcare providers and peer meetings), and reliance on spirituality aided positive coping among these young adults amidst the challenges of living with HIV.

Conclusions

In this rural setting, emerging adults living with HIV face various challenges at the individual, family, and community level, some of which are cross-cutting. Our findings underscore the need for designing multi-level youth-friendly interventions that can address modifiable challenges encountered by emerging adults living with HIV in this and similar settings. Such interventions should incorporate appropriate context-specific support structures that may help these young people smoothly transit into adult life.
Development and validation of a multi-lingual online questionnaire for surveying the COVID-19 prevention and control measures used in global workplaces
Authors: Ingram Carolyn , Chen Yanbing , Buggy Conor , Downey Vicky , Archibald Mary , Rachwal Natalia , Roe Mark , Drummond Anne , Perrotta Carla
Published: January 2022

Background

Despite widespread COVID-19 vaccination programs, there is an ongoing need for targeted disease prevention and control efforts in high-risk occupational settings. This study aimed to develop, pilot, and validate an instrument for surveying occupational COVID-19 infection prevention and control (IPC) measures available to workers in diverse geographic and occupational settings.

Methods

A 44-item online survey was developed in English and validated for face and content validity according to literature review, expert consultation, and pre-testing. The survey was translated and piloted with 890 workers from diverse industries in Canada, Ireland, Argentina, Poland, Nigeria, China, the US, and the UK. Odds ratios generated from univariable, and multivariable logistic regression assessed differences in ‘feeling protected at work’ according to gender, age, occupation, country of residence, professional role, and vaccination status. Exploratory factor analysis (EFA) was conducted, and internal consistency reliability verified with Cronbach’s alpha. Hypothesis testing using two-sample t-tests verified construct validity (i.e., discriminant validity, known-groups technique), and criterion validity.

Results

After adjustment for occupational sector, characteristics associated with feeling protected at work included being male (AOR = 1.88; 95% CI = 1.18,2.99), being over 55 (AOR = 2.17; 95% CI = 1.25,3.77) and working in a managerial position (AOR = 3.1; 95% CI = 1.99,4.83). EFA revealed nine key IPC domains relating to: environmental adjustments, testing and surveillance, education, costs incurred, restricted movements, physical distancing, masking, isolation strategies, and areas for improvement. Each domain showed sufficient internal consistency reliability (Cronbach’s alpha ≥0.60). Hypothesis testing revealed differences in survey responses by country and occupational sector, confirming construct validity (p < 0.001), criterion validity (p = 0.04), and discriminant validity (p < 0.001).

Conclusions

The online survey, developed in English to identify the COVID-19 protective measures used in diverse workplace settings, showed strong face validity, content validity, internal consistency, criterion validity, and construct validity. Translations in Chinese, Spanish, French, Polish, and Hindi demonstrated adaptability of the survey for use in international working environments. The multi-lingual tool can be used by decision makers in the distribution of IPC resources, and to guide occupational safety and health (OSH) recommendations for preventing COVID-19 and future infectious disease outbreaks.
Comprehensive risk assessment for hospital-acquired pneumonia: sociodemographic, clinical, and hospital environmental factors associated with the incidence of hospital-acquired pneumonia
Authors: Kim Bo-Guen , Kang Minwoong , Lim Jihyun , Lee Jin , Kang Danbee , Kim Minjung , Kim Jinhee , Park Hyejeong , Min Kyung Hoon , Cho Juhee , Jeon Kyeongman
Published: January 2022

Background

Social and hospital environmental factors that may be associated with hospital-acquired pneumonia (HAP) have not been evaluated. Comprehensive risk assessment for the incidence of HAP including sociodemographic, clinical, and hospital environmental factors was conducted using national health insurance claims data.

Methods

This is a population-based retrospective cohort study of adult patients who were hospitalized for more than 3 days from the Health Insurance Review and Assessment Service-National Inpatient Sample data between January 1, 2016 and December 31, 2018 in South Korea. Multivariable logistic regression analyses were conducted to identify the factors associated with the incidence of HAP.

Results

Among the 512,278 hospitalizations, we identified 25,369 (5.0%) HAP cases. In multivariable analysis, well-known risk factors associated with HAP such as older age (over 70 vs. 20–29; adjusted odds ratio [aOR], 3.66; 95% confidence interval [CI] 3.36–3.99), male sex (aOR, 1.35; 95% CI 1.32–1.39), pre-existing lung diseases (asthma [aOR, 1.73; 95% CI 1.66–1.80]; chronic obstructive pulmonary disease [aOR, 1.62; 95% CI 1.53–1.71]; chronic lower airway disease [aOR, 1.79; 95% CI 1.73–1.85]), tube feeding (aOR, 3.32; 95% CI 3.16–3.50), suctioning (aOR, 2.34; 95% CI 2.23–2.47), positioning (aOR, 1.63; 95% CI 1.55–1.72), use of mechanical ventilation (aOR, 2.31; 95% CI 2.15–2.47), and intensive care unit admission (aOR, 1.29; 95% CI 1.22–1.36) were associated with the incidence of HAP. In addition, poverty (aOR, 1.08; 95% CI 1.04–1.13), general hospitals (aOR, 1.54; 95% CI 1.39–1.70), higher bed-to-nurse ratio (Grade ≥ 5; aOR, 1.45; 95% CI 1.32–1.59), higher number of beds per hospital room (6 beds; aOR, 3.08; 95% CI 2.77–3.42), and ward with caregiver (aOR, 1.19; 95% CI 1.12–1.26) were related to the incidence of HAP.

Conclusions

The incidence of HAP was associated with various sociodemographic, clinical, and hospital environmental factors. Thus, taking a comprehensive approach to prevent and treat HAP is important.
A prediction rule for severe adverse events in all inpatients with community-acquired pneumonia: a multicenter observational study
Authors: Sakakibara Toshihiro , Shindo Yuichiro , Kobayashi Daisuke , Sano Masahiro , Okumura Junya , Murakami Yasushi , Takahashi Kunihiko , Matsui Shigeyuki , Yagi Tetsuya , Saka Hideo , Hasegawa Yoshinori
Published: January 2022

Background

Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP.

Methods

Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study.

Results

The ALL-COP SCORE rule included albumin (< 2 g/dL, 2 points; 2–3 g/dL, 1 point), white blood cell (< 4000 cells/μL, 3 points), chronic lung disease (1 point), confusion (2 points), PaO2/FIO2 ratio (< 200 mmHg, 3 points; 200–300 mmHg, 1 point), potassium (≥ 5.0 mEq/L, 2 points), arterial pH (< 7.35, 2 points), systolic blood pressure (< 90 mmHg, 2 points), PaCO2 (> 45 mmHg, 2 points), HCO3− (< 20 mmol/L, 1 point), respiratory rate (≥ 30 breaths/min, 1 point), pleural effusion (1 point), and extent of chest radiographical infiltration in unilateral lung (> 2/3, 2 points; 1/2–2/3, 1 point). Patients with 4–5, 6–7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity.

Conclusions

ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points.

Trial registration

This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837.
Enhancing the effectiveness of flipped classroom in health science education: a state-of-the-art review
Authors: Oudbier Janique , Spaai Gerard , Timmermans Karline , Boerboom Tobias
Published: January 2022

Background

In a flipped classroom, students acquire knowledge before class and deepen and apply this knowledge during class. This way, lower-order learning goals are achieved before class and higher-order skills are reached during class. This study aims to provide an overview of the factors that contribute to the effectiveness of the flipped classroom and how these factors can be stimulated. The effectiveness of the flipped classroom is conceptualized in this study as test scores, the achievement of higher learning goals, and student perceptions.

Methods

A state-of-the-art review was conducted. The databases MEDLINE, PsycINFO, PubMed, Web of Science, and Scopus were consulted. The timeframe is 2016 till 2020. The studies were qualitatively analyzed according to the grounded theory method.

Results

After screening the studies based on the inclusion-and exclusion criteria, 88 studies were included in this review. The qualitative analysis of these studies revealed six main factors that affect the effectiveness of the flipped classroom: student characteristics, teacher characteristics, implementation, task characteristics, out-of-class activities, and in-class activities. Mediating factors are, amongst other factors, the learner’s level of self-regulated learning, teacher’s role and motivation, assessment approach, and guidance during self-study by means of prompts or feedback. These factors can be positively stimulated by structuring the learning process and focusing the teacher training on competencies and learning-and teaching approaches that are essential for the flipped classroom.

Conclusion

This paper provides insight into the factors that contribute to the effectiveness of the flipped classroom and how these factors could be stimulated. In order to stimulate the effectiveness of the flipped classroom, the positively and negatively affecting factors and mediating factors should be taken into account in the design of the flipped classroom. The interventions mentioned in this paper could also be used to enhance the effectiveness.
Sequentially calibrating a Bayesian microsimulation model to incorporate new information and assumptions
Authors: DeYoreo Maria , Rutter Carolyn M. , Ozik Jonathan , Collier Nicholson
Published: January 2022

Background

Microsimulation models are mathematical models that simulate event histories for individual members of a population. They are useful for policy decisions because they simulate a large number of individuals from an idealized population, with features that change over time, and the resulting event histories can be summarized to describe key population-level outcomes. Model calibration is the process of incorporating evidence into the model. Calibrated models can be used to make predictions about population trends in disease outcomes and effectiveness of interventions, but calibration can be challenging and computationally expensive.

Methods

This paper develops a technique for sequentially updating models to take full advantage of earlier calibration results, to ultimately speed up the calibration process. A Bayesian approach to calibration is used because it combines different sources of evidence and enables uncertainty quantification which is appealing for decision-making. We develop this method in order to re-calibrate a microsimulation model for the natural history of colorectal cancer to include new targets that better inform the time from initiation of preclinical cancer to presentation with clinical cancer (sojourn time), because model exploration and validation revealed that more information was needed on sojourn time, and that the predicted percentage of patients with cancers detected via colonoscopy screening was too low.

Results

The sequential approach to calibration was more efficient than recalibrating the model from scratch. Incorporating new information on the percentage of patients with cancers detected upon screening changed the estimated sojourn time parameters significantly, increasing the estimated mean sojourn time for cancers in the colon and rectum, providing results with more validity.

Conclusions

A sequential approach to recalibration can be used to efficiently recalibrate a microsimulation model when new information becomes available that requires the original targets to be supplemented with additional targets.
Analysis of the implementation of an innovative IT solution to improve waiting times, communication with primary care and efficiency in Rheumatology
Authors: Pego-Reigosa José María , Peña-Gil Carlos , Rodríguez-Lorenzo David , Altabás-González Irene , Pérez-Gómez Naír , Guzmán-Castro John Henry , Varela-Gestoso Rodrigo , Díaz-Lambarri Reyes , González-Carreró-López Alberto , Míguez-Senra Olga , Bóveda-Fontán Julia , Charle-Crespo Ángeles , Caramés-Casal Francisco Javier , Barbazán-Álvarez Ceferino , Hernández-Rodríguez Íñigo , Maceiras-Pan Francisco , Rodríguez-López Marina , Melero-González Rafael , Rodríguez-Fernández José Benito
Published: January 2022

Objective

To describe in detail an innovative program based on telemedicine for semi-automated prioritization of referrals from Primary Care (PC) to Rheumatology, for reproducibility purposes, and to present the results of the implementation study.

Methods

The context and situation were carefully analyzed, paying attention to all processes in place, referral numbers, waiting times, and number of complementary tests prior to discharge from Rheumatology. The composition of the team, aims, users, scope, and implementation phases were defined. Eight process indicators were established and measured before and 32 months after the program implementation.

Results

The program, which includes IT circuits, algorithms based on response to specific guideline-based checklists, e-consultation, and appointments based on priority, was fully implemented in our health area after a pilot study in two PC centers. After implementation, 6185 rheumatology referrals showed an e-consultation response delay of 8.95 days, and to first face-to-face visit (after e-consultation) of 12.6 (previous delay before program implementation was 83.1 days). Resolution by e-consultation reached 20% (1195 patients did not need seeing the rheumatologist to have the problem solved), and 1369 patients (32%) were discharged after the first visit. The overall resolution rate was 44.0% (2564 discharges/5830 e-consultations). From a random sample of 100 visits, only 10% of patients needed additional complementary tests to make a diagnosis and decision by Rheumatology (20.9% decrease from previous period).

Conclusion

A careful analysis of the situation and processes, with implementation of simple IT circuits, allows for the improvement of the efficiency and resolution of problems in Rheumatology.
Respiratory system compliance at the same PEEP level is similar in COVID and non-COVID ARDS
Authors: Fusina Federica , Albani Filippo , Crisci Serena , Morandi Alessandro , Tansini Francesca , Beschi Rasula , Rosano Antonio , Natalini Giuseppe
Published: January 2022

Background

The comparison of respiratory system compliance (Crs) between COVID and non-COVID ARDS patients has been the object of debate, but few studies have evaluated it when considering applied positive end expiratory pressure (PEEP), which is one of the known determinants of Crs itself. The aim of this study was to compare Crs taking into account the applied PEEP.

Methods

Two cohorts of patients were created: those with COVID-ARDS and those with non-COVID ARDS. In the whole sample the association between Crs and type of ARDS at different PEEP levels was adjusted for anthropometric and clinical variables. As secondary analyses, patients were matched for predicted functional residual capacity and the same association was assessed. Moreover, the association between Crs and type of ARDS was reassessed at predefined PEEP level of 0, 5, 10, and 15 cmH2O with a propensity score-weighted linear model.

Results

367 patients were included in the study, 276 patients with COVID-ARDS and 91 with non-COVID ARDS. The association between Crs and type of ARDS was not significant in both the complete cohorts (p = 0.17) and in the matched cohorts (p = 0.92). This was true also for the propensity score weighted association at PEEP 5, 10 and 15 cmH2O, while it was statistically significant at PEEP 0 (with a median difference of 3 ml/cmH2O, which in our opinion is not clinically significant).

Conclusions

The compliance of the respiratory system is similar between COVID ARDS and non-COVID ARDS when calculated at the same PEEP level and while taking into account patients’ anthropometric characteristics.
Intersectional inequalities in younger women’s experiences of physical intimate partner violence across communities in Bangladesh
Authors: Rahman Laila , Du Mont Janice , O’Campo Patricia , Einstein Gillian
Published: January 2022

Background

Physical intimate partner violence (IPV) risk looms large for younger women in Bangladesh. We are, however, yet to know the association between their intersectional social locations and IPV across communities. Drawing on intersectionality theory’s tenet that interacting systems of power, oppressions, and privileges work together, we hypothesized that (1)younger, lower educatedorpoorwomen’s physical IPV experiences will be exacerbated in disadvantaged communities; and conversely, (2)younger, higher educatedornonpoorwomen’s physical IPV experiences will be ameliorated in advantaged communities.

Methods

We applied intercategorical intersectionality analyses using multilevel logistic regression models in 15,421 currently married women across 911 communities from a national, cross-sectional survey in 2015. To test the hypotheses, women’s probabilities of currently experiencing physical IPV among intersectional social groups were compared. These comparisons were made, at first, within each type of disadvantaged (e.g., younger or poor) and advantaged (e.g., older or nonpoor) communities; and then, between different types of communities.

Results

While our specific hypotheses were not supported, we found significant within community differences, suggesting thatyounger, lower educated or poorwomen were bearing the brunt of IPV in almost every community (probabilities ranged from 34.0–37.1%).Younger, poorcompared toolder, nonpoorwomen had significantly higher IPV probabilities (the minimum difference = 12.7, 95% CI, 2.8, 22.6) in all communities. Similar trend was observed betweenyounger, lower educatedcompared toolder, higher educatedwomen in all except communities that were poor. Interestingly, younger women’s advantage of higher education and material resources compared to their lower educated or poor counterparts was observed only in advantaged communities. However, these within community differences did not vary between disadvantaged and advantaged communities (difference-in-differences ranged from − 0.9%, (95% CI, − 8.5, 6.7) to − 8.6%, (95% CI, − 17.6, 0.5).

Conclusions

Using intersectionality theory made visible the IPV precarity of younger, lower educated or poor women across communities. Future research might examine the structures and processes that put them at these precarious locations to ameliorate their socio-economic-educational inequalities and reduce IPV in all communities. For testing hypotheses using intersectionality theory, this study might advance scholarship on physical IPV in Bangladesh and quantitative intersectionality globally.
Socio-economic determinants of healthcare costs in early life: a register-based study in the Netherlands
Authors: van der Hulst Marije , Polinder Suzanne , Kok Rianne , Prinzie Peter , de Groot Marijke W. , Burdorf Alex , Bertens Loes C. M.
Published: January 2022

Background

Children with low socioeconomic status (SES) have an increased risk of a suboptimal start in life with ensuing higher healthcare costs. This study aims to investigate the effects of individual- (monthly household income) and contextual-level SES (household income and neighborhood deprivation), and perinatal morbidity (preterm birth and small for gestational age ((<10th percentile), SGA)) on healthcare costs in early life (0–3 years of age).

Methods

Individual-linked data from three national registries (Perinatal Registry Netherlands, Statistics Netherlands, and Healthcare Vektis) were obtained of all children born between 2011 and 2014 (N = 480,471) in the Netherlands. Binomial logistic regression was used to model annual healthcare costs as a function of their household income (per €1000), neighborhood deprivation index (range − 13.26 – 10.70), their perinatal morbidity and demographic characteristics. Annual healthcare cost were dichotomized into low healthcare costs (Q1-Q3 below €1000) and high healthcare costs (Q4 €1000 or higher).

Results

Children had a median of €295 annual healthcare costs, ranging from €72 to €4299 (5–95%). Binomial logistic regression revealed that for every €1000 decrease in monthly household income, the OR for having high healthcare costs is 0.99 (0.99–0.99). Furthermore, for every one-unit increase in neighborhood deprivation the OR for having high healthcare costs increase 1.02 (1.01–1.02). Finally, the model revealed an OR of 2.55 (2.48–2.61) for preterm born children, and an OR of 1.44 (1.41–1.48) for children SGA, to have high healthcare costs compared to their healthy peers.

Conclusion

More neighborhood deprivation was directly related to higher healthcare costs in young children. On top of this, lower household income was consistently and independently related to higher healthcare costs. By optimizing conditions for low SES populations, the impact of low SES circumstances on their healthcare costs can be positively influenced. Additionally, policies that influence more timely and appropriate healthcare use in low SES populations can reduce healthcare costs further.
Na+/Ca2+ exchanger isoform 1 takes part to the Ca2+-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-l-alanine
Authors: Petrozziello Tiziana , Boscia Francesca , Tedeschi Valentina , Pannaccione Anna , de Rosa Valeria , Corvino Angela , Severino Beatrice , Annunziato Lucio , Secondo Agnese
Published: January 2022

Background

The cycad neurotoxin beta-methylamino-l-alanine (L-BMAA), one of the environmental trigger factor for amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC), may cause neurodegeneration by disrupting organellar Ca2+ homeostasis. Through the activation of Akt/ERK1/2 pathway, the Cu,Zn-superoxide dismutase (SOD1) and its non-metallated form, ApoSOD1, prevent endoplasmic reticulum (ER) stress-induced cell death in motor neurons exposed to L-BMAA. This occurs through the rapid increase of intracellular Ca2+ concentration ([Ca2+]i) in part flowing from the extracellular compartment and in part released from ER. However, the molecular components of this mechanism remain uncharacterized.

Methods

By an integrated approach consisting on the use of siRNA strategy, Western blotting, confocal double- labeling immunofluorescence, patch-clamp electrophysiology, and Fura 2-/SBFI-single-cell imaging, we explored in rat motor neuron-enriched cultures the involvement of the plasma membrane proteins Na+/Ca2+ exchanger (NCX) and purinergic P2X7 receptor as well as that of the intracellular cADP-ribose (cADPR) pathway, in the neuroprotective mechanism of SOD1.

Results

We showed that SOD1-induced [Ca2+]i rise was prevented neither by A430879, a P2X7 receptor specific antagonist or 8-bromo-cADPR, a cell permeant antagonist of cADP-ribose, but only by the pan inhibitor of NCX, CB-DMB. The same occurred for the ApoSOD1. Confocal double labeling immunofluorescence showed a huge expression of plasmalemmal NCX1 and intracellular NCX3 isoforms. Furthermore, we identified NCX1 reverse mode as the main mechanism responsible for the neuroprotective ER Ca2+ refilling elicited by SOD1 and ApoSOD1 through which they promoted translocation of active Akt in the nuclei of a subset of primary motor neurons. Finally, the activation of NCX1 by the specific agonist CN-PYB2 protected motor neurons from L-BMAA-induced cell death, mimicking the effect of SOD1.

Conclusion

Collectively, our data indicate that SOD1 and ApoSOD1 exert their neuroprotective effect by modulating ER Ca2+ content through the activation of NCX1 reverse mode and Akt nuclear translocation in a subset of primary motor neurons.
Sublethal enteroviral infection exacerbates disease progression in an ALS mouse model
Authors: Xue Yuan Chao , Liu Huitao , Mohamud Yasir , Bahreyni Amirhossein , Zhang Jingchun , Cashman Neil R. , Luo Honglin
Published: January 2022

Background

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor neuron system associated with both genetic and environmental risk factors. Infection with enteroviruses, including poliovirus and coxsackievirus, such as coxsackievirus B3 (CVB3), has been proposed as a possible causal/risk factor for ALS due to the evidence that enteroviruses can target motor neurons and establish a persistent infection in the central nervous system (CNS), and recent findings that enteroviral infection-induced molecular and pathological phenotypes closely resemble ALS. However, a causal relationship has not yet been affirmed.

Methods

Wild-type C57BL/6J and G85R mutant superoxide dismutase 1 (SOD1G85R) ALS mice were intracerebroventricularly infected with a sublethal dose of CVB3 or sham-infected. For a subset of mice, ribavirin (a broad-spectrum anti-RNA viral drug) was given subcutaneously during the acute or chronic stage of infection. Following viral infection, general activity and survival were monitored daily for up to week 60. Starting at week 20 post-infection (PI), motor functions were measured weekly. Mouse brains and/or spinal cords were harvested at day 10, week 20 and week 60 PI for histopathological evaluation of neurotoxicity, immunohistochemical staining of viral protein, neuroinflammatory/immune and ALS pathology markers, and NanoString and RT-qPCR analysis of inflammatory gene expression.

Results

We found that sublethal infection (mimicking chronic infection) of SOD1G85R ALS mice with CVB3 resulted in early onset and progressive motor dysfunction, and shortened lifespan, while similar viral infection in C57BL/6J, the background strain of SOD1G85R mice, did not significantly affect motor function and mortality as compared to mock infection within the timeframe of the current study (60 weeks PI). Furthermore, we showed that CVB3 infection led to a significant increase in proinflammatory gene expression and immune cell infiltration and induced ALS-related pathologies (i.e., TAR DNA-binding protein 43 (TDP-43) pathology and neuronal damage) in the CNS of both SOD1G85R and C57BL/6J mice. Finally, we discovered that early (day 1) but not late (day 15) administration of ribavirin could rescue ALS-like neuropathology and symptoms induced by CVB3 infection.

Conclusions

Our study identifies a new risk factor that contributes to early onset and accelerated progression of ALS and offers opportunities for the development of novel targeted therapies.