bluuebunny/crossref_metadata_2025 huggingface dataset:
Data sources for precision public health of obesity: a scoping review, evidence map and use case in Queensland, Australia
Authors: Canfell Oliver J. , Davidson Kamila , Sullivan Clair , Eakin Elizabeth , Burton-Jones Andrew
Published: March 2022

Background

Global action to reduce obesity prevalence requires digital transformation of the public health sector to enable precision public health (PPH). Useable data for PPH of obesity is yet to be identified, collated and appraised and there is currently no accepted approach to creating this single source of truth. This scoping review aims to address this globally generic problem by using the State of Queensland (Australia) (population > 5 million) as a use case to determine (1) availability of primary data sources usable for PPH for obesity (2) quality of identified sources (3) general implications for public health policymakers.

Methods

The Preferred Reporting Items for Systematic Review and Meta-Analyses extension for scoping reviews (PRISMA-ScR) was followed. Unique search strategies were implemented for ‘designed’ (e.g. surveys) and ‘organic’ (e.g. electronic health records) data sources. Only primary sources of data (with stratification to Queensland) with evidence-based determinants of obesity were included. Primary data source type, availability, sample size, frequency of collection and coverage of determinants of obesity were extracted and curated into an evidence map. Data source quality was qualitatively assessed.

Results

We identified 38 primary sources of preventive data for obesity: 33 designed and 5 organic. Most designed sources were survey (n 20) or administrative (n 10) sources and publicly available but generally were not contemporaneous (> 2 years old) and had small sample sizes (10-100 k) relative to organic sources (> 1 M). Organic sources were identified as the electronic medical record (ieMR), wearables, environmental (Google Maps, Crime Map) and billing/claims. Data on social, biomedical and behavioural determinants of obesity typically co-occurred across sources. Environmental and commercial data was sparse and interpreted as low quality. One organic source (ieMR) was highly contemporaneous (routinely updated), had a large sample size (5 M) and represented all determinants of obesity but is not currently used for public health decision-making in Queensland.

Conclusions

This review provides a (1) comprehensive data map for PPH for obesity in Queensland and (2) globally translatable framework to identify, collate and appraise primary data sources to advance PPH for obesity and other noncommunicable diseases. Significant challenges must be addressed to achieve PPH, including: using designed and organic data harmoniously, digital infrastructure for high-quality organic data, and the ethical and social implications of using consumer-centred health data to improve public health.
Measuring physical, cognitive, and emotional aspects of exhaustion with the BOSS II-short version – results from a representative population-based study in Germany
Authors: Werner Antonia M. , Schmalbach Bjarne , Zenger Markus , Brähler Elmar , Hinz Andreas , Kruse Johannes , Kampling Hanna
Published: March 2022

Background

The aim of the present study was the construction and psychometric evaluation of a shortened version of the Burnout Screening Scales II (BOSS II), a measure for exhaustion and burnout.

Methods

To this end, among a representative sample of the German general population (N = 2429, 52.9% women), we shortened the scale from 30 to 15 items applying ant-colony-optimization, and calculated item statistics of the short version (BOSS II-short). To estimate its reliability, we used McDonald’s Omega (ω). To demonstrate validity, we compared the correlation between the BOSS II-short and the BOSS II, as well as their associations with depression, anxiety, and quality of life. Furthermore, we evaluated model fit and measurement invariance across respondent age and gender in confirmatory factor analyses (CFA). Finally, we present adapted norm values.

Results

The CFA showed an excellent model fit (χ2 = 223.037, df = 87, p < .001; CFI = .975; TLI = .970; RMSEA [90%CI] = .036 [.031;.040]) of the BOSS II-short, and good to very good reliability of the three subscales: ‘physical’ (ω = .76), ‘cognitive’ (ω = .89), and ‘emotional’ (ω = .88) symptoms. There was strict measurement invariance for male and female participants and partial strict invariance across age groups. Each subscale was negatively related to quality of life (‘physical’: r = −.62; ‘cognitive’: r = −.50; ‘emotional’: r = −.50), and positively associated with depression (‘physical’: r = .57; ‘cognitive’: r = .67; ‘emotional’: r = .73) and anxiety (‘physical’: r = .50; ‘cognitive’: r = .63; ‘emotional’: r = .71).

Conclusions

Overall, the BOSS II-short proved to be a valid and reliable instrument in the German general population allowing a brief assessment of different symptoms of exhaustion. Norm values can be used for early detection of exhaustion.
The wellbeing needs of social housing tenants in Australia: an exploratory study
Authors: Freund Megan , Sanson-Fisher Robert , Adamson David , Norton Grace , Hobden Breanne , Clapham Matthew
Published: March 2022

Background

Social housing provides homes for some of the most vulnerable in society. Those in social housing often have complex issues that may require support. Limited research has examined the unmet needs of those living in social housing from the tenant perspective. This exploratory study aimed to embark on filling this gap.

Methods

A cross-sectional study survey of adult social housing tenants in New South Wales, Australia. Consenting tenants completed a survey asking about their support needs across five domains: transport, employment and financial stress; housing and safety; health and health behaviour; access to services; and control over one’s life. Negative binomial regression analysis was used to examine associations between the mean number of support needs and characteristics.

Results

Of the 104 tenants invited, 101 agreed to participate (97%) of which 100 completed the survey. Paying unexpected bills’ (43%), feeling sad or anxious (40%), feelings of anger or frustration (34%), and memory or concentration problems (33%) were the most prevalent reported needs. Other needs included antisocial behaviour from neighbours (31%) and having control in the direction your life is taking (27%). Seventy-five percent of tenants reported at least one need, with an average of seven needs across the sample (median 5.5, range 0–24). Tenants who identified as Aboriginal or Torres Strait Islander had a higher number of needs compared to other tenants (RR 1.87 95% CI 1.08 to 3.35).

Conclusions

More research describing tenant wellbeing needs is required to guide initiatives improving tenant wellbeing. Development of a standardised tool to measure and prioritise tenant wellbeing needs would be beneficial. There is a need for well-controlled research to establish the potential effectiveness and cost effectiveness of initiatives implemented at the policy or housing provider level. Future research must consider the multifaceted needs of this population. Further, Aboriginal and Torres Strait Islander people are generally overrepresented in social housing in Australia, and in this study Aboriginal and Torres Strait Islander tenants reported a higher number of needs compared to non-Aboriginal and Torres Strait Islander tenants. Given this, future research should ensure measurement tools or strategy initiatives are culturally sensitive and appropriate, and are developed in collaboration with Aboriginal and Torres Strait Islander communities.
Who is accessing community lateral flow device testing and why? Characteristics and motivations of individuals participating in COVID-19 community testing in two English local authority areas
Authors: Dalili Michael N. , Long Jo , Wadley Emma , Sloan Jack , Cross Andrew , Thomas Kyla H. , Morgan Gemma
Published: March 2022

Background

Antigen testing using lateral flow devices (LFDs) plays an important role in the management of the novel coronavirus pandemic of 2019 (COVID-19) by rapidly identifying individuals who are asymptomatically carrying high levels of the virus. By January 2021, LFD community testing sites were set up across English local authority areas to support the management and containment of regional COVID-19 cases, initially targeting essential workers unable to work from home during the national lockdown. This study aimed to examine the characteristics and motivations of individuals accessing community LFD testing across two local authority areas (LAAs) in the South West of England.

Methods

Data were collected as part of a service evaluation from December 22nd 2020 until March 15th 2021 for two LAAs. Demographic and postcode data were collected from an online test appointment booking platform and the National Health Service testing service online system, with data accessed from Public Health England. An online survey was sent to individuals who made a testing appointment at an LAA1 site using the online booking platform, consisting of 12 questions to collect data on individual’s motivations for and experiences of testing.

Results

Data were available for individuals who completed 12,516 tests in LAA1 and 12,327 tests in LAA2. Most individuals who engaged with testing were female, working age, white, and worked as early years or education staff, health and social care staff, and supermarket or food production staff. 1249 individuals completed the survey with 60% of respondents reported getting tested for work-related reasons. Individuals first heard about LFD testing through various channels including work, media, and word of mouth, and decided to get tested based on the ease and convenience of testing, workplace communications, and to identify asymptomatic cases to help stop the spread. Most tests were completed by individuals living in less deprived areas based on national deciles of deprivation.

Conclusions

While national and local COVID-19 testing strategies have evolved, community and personal LFD testing remains a crucial pillar of the testing strategy. Future studies should collect quantitative and qualitative data from residents to most effectively shape testing offers based on the needs and preferences of their population.
Exploring the factors affecting preschool educators’ health teaching capacity of life skills using the PRECEDE model: a study of preschool educators in northern Taiwan
Authors: Chen Hui Ling , Huang Wei Hsiang , Liu Chieh Hsing
Published: March 2022

Background

The purpose of this study was to apply the Predisposing, Reinforcing, and Enabling Constructs in Educational Diagnosis and Evaluation (PRECEDE) model to analyze the factors influencing preschool educators’ ability to teach health education through life skills.

Methods

This cross-sectional study utilized stratified random sampling and administered survey questionnaires to 503 preschool educators in public and private kindergartens in Taipei City and New Taipei City in 2019. Descriptive and hierarchical regression analyses were conducted. The PRECEDE model demonstrated a significant correlation between the enabling, reinforcing, and predisposing factors explored in this study and the preschool educators’ ability to teach health education through life skills.

Results

The variables explained 25% of the total variance in the ability to teach health education through life skills. When controlled in individual layers, the background variables and the enabling, reinforcing, and predisposing factors demonstrated explanatory powers of 6, 5, 7, and 7%, respectively, with respect to the ability to teach health education by utilizing life skills.

Conclusions

Enhancement of the enabling, reinforcing, and predisposing factors can improve preschool educators’ ability to teach health education through life skills. The support provided by the governmental policies for related training can facilitate the effective implementation of health promotion programs in kindergartens. Preschool educators must also receive on-the-job training to facilitate the effective transaction of the health education curriculum. Health classes centered on life skills in kindergartens are vital and must be incorporated into the curricula.
The MLR, NLR, PLR and D-dimer are associated with clinical outcome in lung cancer patients treated with surgery
Authors: Wang Jun , li Huawei , Xu Ran , Lu Tong , Zhao Jiaying , Zhang Pengfei , Qu Lidong , Zhang Shengqiang , Guo Jida , Zhang Linyou
Published: March 2022

Objective

The study objective was to investigate the use of peripheral blood biomarkers as predictors of patient survival. The aim of this study was to identify the baseline peripheral blood biomarkers associated with clinical outcome in patients with early lung cancer (stage I-II) treated with surgery.

Methods

We included and analysed data from 376 patients with early-stage lung cancer who underwent a standard lobectomy. Univariate and multivariate Cox regression analyses were performed on all patients to assess the relationships between progression-free survival (PFS) and overall survival (OS) and the peripheral blood biomarker metrics measured before surgical treatment. The peripheral blood parameters included monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and dimeric fibrin fragment D (D-dimer).

Results

After univariate Cox regression analysis, low MLR, low NLR, low PLR and low D-dimer values were significantly associated with both better OS and PFS (all p < 0.05). In multivariate Cox regression analysis, a low MLR was significantly and independently associated with both better overall survival and better progression-free survival (both p <0.05). A low D-dimer level was significantly and independently associated with better overall survival (p <0.05). Furthermore, the categorization of patients according to the number of factors with favourable results revealed that those without favourable results had significantly worse outcomes than that of those patients with at least one.

Conclusion

A baseline signature of low MLR, low NLR, low PLR, and low D-dimer values was associated with a better survival outcome for patients treated with surgery. Patients with more favourable results had better survival outcomes.
Comparison of arthroscopy versus percutaneous radiofrequency thermal ablation for the management of intra- and juxta-articular elbow osteoid osteoma: case series and a literature review
Authors: Knežević Igor , Bojanić Ivan
Published: March 2022

Background

Today, intra-articular and juxta-articular osteoid osteomas are treated with arthroscopy and radiofrequency thermal ablation. However, for the case of an elbow joint, arguments are made for the use of a minimally invasive technique to be the optimal choice. This study aims to analyse our experiences of arthroscopically treated elbow osteoid osteomas and to compare it with the published results of both techniques.

Methods

The retrospective study analyses the patients who underwent elbow arthroscopy ablation of an elbow osteoid osteoma at a single institution from January 2014 until March 2020. Clinical and diagnostic features, success and treatment failure rates, complications and tumour recurrence rates were all compared to 13 studies of intra-articular elbow osteoid osteoma arthroscopic ablation and 15 studies involving radiofrequency thermal ablation of intra-articular osteoid osteoma within different joints.

Results

Four males and two females, with a mean age of 19.3 years, were encompassed. All the patients had immediate postoperative pain relief and improved range of motion. No tumour recurrences were observed during a median of 21.7 months. The literature review yielded 86.4% success rate, 68.2% successful biopsies, one minor complication and no recurrences following the arthroscopic ablation of an elbow osteoid osteoma; while radiofrequency thermal ablation of an intra-articular elbow osteoid osteoma yielded 96.3% success rate, 33.3% successful biopsies, no complications and 3.7% recurrence rate.

Conclusions

Our results are consistent with the published literature proving that arthroscopic ablation is an efficient method with low treatment failure rates and no recurrences in treating intra- and juxta-articular elbow osteoid osteomas. Advantages of arthroscopic ablation stem from the ability to visualise and safely deal with the lesion and the joint’s reactive changes resulting in high biopsy rates, no recurrences and better postoperative elbow’s range of motion. Still, the technique selection should be personalised considering the medical expertise of every institution.
Could screw/hook insertion at the apical vertebrae with rib head dislocation effectively retract the corresponding rib head from spinal canal in dystrophic scoliosis secondary to type 1 neurofibromatosis?
Authors: Li Song , Mao Saihu , Ma Yanyu , Shi Ben-long , Liu Zhen , Zhu Ze-zhang , Qiao Jun , Qiu Yong
Published: March 2022

Background

Rib head dislocation (RHD) in dystrophic scoliosis of type 1 neurofibromatosis (DS-NF1) is a unique disorder caused by skeletal dystrophy and scoliotic instability. No particular surgical manipulation is mentioned in the literature to instruct the spine surgeons to effectively obtain more migration of the dislocated rib head without resection. The present study aimed to investigate the effectiveness of screw/hook insertion at vertebrae with RHDs on the retraction of penetrated rib head from spinal canal.

Methods

37 neurologically intact patients with DS-NF1 and concomitant 53 RHDs undergoing scoliosis surgery without rib head excision were retrospectively reviewed. We used pre and postoperative whole-spine radiographs to determine the Cobb angle and the vertebral translation (VT), and the CT scans to evaluate the intraspinal rib length (IRL) and rib-vertebral angle (RVA). The dislocated ribs were assigned into two groups according to the presence of screw/hook insertion at vertebrae with RHD: screw/hook group and non-screw/hook group.

Results

37 dislocated ribs with screws/hooks insertion at corresponding vertebrae were assigned into the screw/hook group and the remaining 16 dislocated ribs consisted of the non-screw/hook group. In the screw/hook group, the correction rates of Cobb angle and VT were significantly higher than the non-screw/hook group after surgery (58.7 ± 16.0% vs. 30.9 ± 12.4%, p = 0.003; 61.8 ± 18.8% vs. 35.1 ± 16.6%, p = 0.001; respectively). Similarly, more correction rates of IRL and RVA were found in the screw/hook group than the non-screw/hook group (63.1 ± 31.3% vs. 30.1 ± 20.7%, p = 0.008; 17.6 ± 9.7% vs. 7.2 ± 3.6%, p = 0.006; respectively). Multiple linear regression analysis revealed that the correction rates of Cobb angle, VT and RVA contributed significantly to correction of IRL (β = 0.389, 0.939 and 1.869, respectively; p = 0.019, 0.001 and 0.002, respectively).

Conclusion

Screw/hook insertion at dystrophic vertebrae with RHDs contributed significantly to the degree of retraction of penetrated rib head from spinal canal. This effectiveness is mediated by more corrections of VT and RVA.
Application of objective structured clinical examination (OSCE) for the evaluation of Kampo medicine training
Authors: Amitani Marie , Amitani Haruka , Suzuki Hajime , Kawazu Suguru , Mizuma Kimiko , Yamaguchi Kojiro , Oki Toshimichi , Nitta Hideaki , Sonoda Takuro , Kawano Keiko , Tanaka Yasuhiro , Uto Nanami , Ibusuki Rie , Arita Ryutaro , Takayama Shin , Mitsuma Tadamichi , Takezaki Toshiro , Asakawa Akihiro , Owaki Tetsuhiro
Published: March 2022

Background

The purpose of this study was to develop an objective, content-valid, and reliable assessment method for Kampo medicine using an objective structured clinical examination (OSCE) for the assessment of clinical competence in Kampo medicine.

Methods

We developed a blueprint followed by a list of 47 assessment items and three task scenarios related to clinical competence in Kampo medicine. An eight-member test committee checked the relevance of the assessment items on a Likert scale. We calculated a content validity index and content validity ratio, and used the Angoff method to set the passing threshold. We trained a total of nine simulated patients with three assigned to each scenario. We conducted an OSCE for 11 candidates with varying medical abilities, and conducted three stations per person, which were evaluated by one evaluator in one room by direct observation. We used video recordings to test the inter-rater reliability of the three raters. We used the test results to verify the reliability of the assessment chart.

Results

The inter-rater reliability (intraclass correlation coefficient [2,1]) was 0.973. The reliability of the assessment chart for each scenario (Cronbach’s α) was 0.86, 0.89, and 0.85 for Scenarios 1, 2, and 3, respectively. The reliability of the assessment chart for the whole OSCE (Cronbach’s α) was 0.90.

Conclusions

We developed a content-valid new OSCE assessment method for Kampo medicine and obtained high inter-rater and test reliabilities. Our findings suggest that this is one of the most reliable evaluation methods for assessing clinical competence in Kampo medicine.
Explainable machine learning to predict long-term mortality in critically ill ventilated patients: a retrospective study in central Taiwan
Authors: Chan Ming-Cheng , Pai Kai-Chih , Su Shao-An , Wang Min-Shian , Wu Chieh-Liang , Chao Wen-Cheng
Published: March 2022

Background

Machine learning (ML) model is increasingly used to predict short-term outcome in critically ill patients, but the study for long-term outcome is sparse. We used explainable ML approach to establish 30-day, 90-day and 1-year mortality prediction model in critically ill ventilated patients.

Methods

We retrospectively included patients who were admitted to intensive care units during 2015–2018 at a tertiary hospital in central Taiwan and linked with the Taiwanese nationwide death registration data. Three ML models, including extreme gradient boosting (XGBoost), random forest (RF) and logistic regression (LR), were used to establish mortality prediction model. Furthermore, we used feature importance, Shapley Additive exPlanations (SHAP) plot, partial dependence plot (PDP), and local interpretable model-agnostic explanations (LIME) to explain the established model.

Results

We enrolled 6994 patients and found the accuracy was similar among the three ML models, and the area under the curve value of using XGBoost to predict 30-day, 90-day and 1-year mortality were 0.858, 0.839 and 0.816, respectively. The calibration curve and decision curve analysis further demonstrated accuracy and applicability of models. SHAP summary plot and PDP plot illustrated the discriminative point of APACHE (acute physiology and chronic health exam) II score, haemoglobin and albumin to predict 1-year mortality. The application of LIME and SHAP force plots quantified the probability of 1-year mortality and algorithm of key features at individual patient level.

Conclusions

We used an explainable ML approach, mainly XGBoost, SHAP and LIME plots to establish an explainable 1-year mortality prediction ML model in critically ill ventilated patients.
Concepts of health in different contexts: a scoping review
Authors: van Druten V. P. , Bartels E. A. , van de Mheen D. , de Vries E. , Kerckhoffs A. P. M. , Nahar-van Venrooij L. M. W.
Published: March 2022

The rationale of our study was that the World Health Organization’s (WHO) definition of health from 1947 which includes “… complete physical, mental and social wellbeing…” does not fit the current societal viewpoints anymore. The WHO’s definition of health implies that many people with chronic illnesses or disabilities would be considered unhealthy and complete wellbeing would be utopian and unfeasible for them. This is no longer uniformly accepted. Many alternative concepts of health have been discussed in the last decades such as ‘positive health’, which focusses on someone’s capability rather than incapability,. However, the question remains whether a general health concept can guide all healthcare practices. More likely, health concepts need to be specified for professions or settings. The objective of our study was to create a structured overview of published concepts of health from different perspectives by conducting a scoping review using the PRISMA-ScR guideline. A literature search was conducted in Pubmed and Cinahl. Articles eligible for inclusion focussed on the discussion or the conceptualisation of health or health-related concepts in different contexts (such as the perspective of care workers’ or patients’) published since 2009 (the Dutch Health Council raised the discussion about moving towards a more dynamic perspective on health in that year). Seventy-five articles could be included for thematic analyses. The results showed that most articles described a concept of health consisting of multiple subthemes; no consensus was found on one overall concept of health. This implies that healthcare consumers act based on different health concepts when seeking care than care workers when providing care. Having different understandings of the concepts of health can lead to misunderstandings in practice. In conclusion, from every perspective, and even for every individual, health may mean something different. This finding stresses the importance that care workers’ and healthcare consumers’ meaning of ‘health’ has to be clear to all actors involved. Our review supports a more uniform tuning of healthcare between healthcare providers (the organisations), care workers (the professionals) and healthcare consumers (the patients), by creating more awareness of the differences among these actors, which can be a guide in their communication.
An extensional strain sensing mechanosome drives adhesion-independent platelet activation at supraphysiological hemodynamic gradients
Authors: Zainal Abidin Nurul A. , Poon Eric K. W. , Szydzik Crispin , Timofeeva Mariia , Akbaridoust Farzan , Brazilek Rose J. , Tovar Lopez Francisco J. , Ma Xiao , Lav Chitrarth , Marusic Ivan , Thompson Philip E. , Mitchell Arnan , Ooi Andrew S. H. , Hamilton Justin R. , Nesbitt Warwick S.
Published: March 2022

Background

Supraphysiological hemodynamics are a recognized driver of platelet activation and thrombosis at high-grade stenosis and in blood contacting circulatory support devices. However, whether platelets mechano-sense hemodynamic parameters directly in free flow (in the absence of adhesion receptor engagement), the specific hemodynamic parameters at play, the precise timing of activation, and the signaling mechanism(s) involved remain poorly elucidated.

Results

Using a generalized Newtonian computational model in combination with microfluidic models of flow acceleration and quasi-homogenous extensional strain, we demonstrate that platelets directly mechano-sense acute changes in free-flow extensional strain independent of shear strain, platelet amplification loops, von Willebrand factor, and canonical adhesion receptor engagement. We define an extensional strain sensing “mechanosome” in platelets involving cooperative Ca2+ signaling driven by the mechanosensitive channel Piezo1 (as the primary strain sensor) and the fast ATP gated channel P2X1 (as the secondary signal amplifier). We demonstrate that type II PI3 kinase C2α activity (acting as a “clutch”) couples extensional strain to the mechanosome.

Conclusions

Our findings suggest that platelets are adapted to rapidly respond to supraphysiological extensional strain dynamics, rather than the peak magnitude of imposed wall shear stress. In the context of overall platelet activation and thrombosis, we posit that “extensional strain sensing” acts as a priming mechanism in response to threshold levels of extensional strain allowing platelets to form downstream adhesive interactions more rapidly under the limiting effects of supraphysiological hemodynamics.
Combined impact of lipidomic and genetic aberrations on clinical outcomes in metastatic castration-resistant prostate cancer
Authors: Mak Blossom , Lin Hui-Ming , Kwan Edmond M. , Fettke Heidi , Tran Ben , Davis Ian D. , Mahon Kate , Stockler Martin R. , Briscoe Karen , Marx Gavin , Zhang Alison , Crumbaker Megan , Tan Winston , Huynh Kevin , Meikle Thomas G. , Mellett Natalie A. , Hoy Andrew J. , Du Pan , Yu Jianjun , Jia Shidong , Joshua Anthony M. , Waugh David J. , Butler Lisa M. , Kohli Manish , Meikle Peter J. , Azad Arun A. , Horvath Lisa G.
Published: March 2022

Background

Both changes in circulating lipids represented by a validated poor prognostic 3-lipid signature (3LS) and somatic tumour genetic aberrations are individually associated with worse clinical outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). A key question is how the lipid environment and the cancer genome are interrelated in order to exploit this therapeutically. We assessed the association between the poor prognostic 3-lipid signature (3LS), somatic genetic aberrations and clinical outcomes in mCRPC.

Methods

We performed plasma lipidomic analysis and cell-free DNA (cfDNA) sequencing on 106 men with mCRPC commencing docetaxel, cabazitaxel, abiraterone or enzalutamide (discovery cohort) and 94 men with mCRPC commencing docetaxel (validation cohort). Differences in lipid levels between men ± somatic genetic aberrations were assessed with t-tests. Associations between the 3LS and genetic aberrations with overall survival (OS) were examined using Kaplan-Meier methods and Cox proportional hazard models.

Results

The 3LS was associated with shorter OS in the discovery (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.4-3.3, p < 0.001) and validation cohorts (HR 2.32, 95% CI 1.59–3.38, p < 0.001). Elevated plasma sphingolipids were associated with AR, TP53, RB1 and PI3K aberrations (p < 0.05). Men with both the 3LS and aberrations in AR, TP53, RB1 or PI3K had shorter OS than men with neither in both cohorts (p ≤ 0.001). The presence of 3LS and/or genetic aberration was independently associated with shorter OS for men with AR, TP53, RB1 and PI3K aberrations (p < 0.02). Furthermore, aggressive-variant prostate cancer (AVPC), defined as 2 or more aberrations in TP53, RB1 and/or PTEN, was associated with elevated sphingolipids. The combination of AVPC and 3LS predicted for a median survival of ~12 months. The relatively small sample size of the cohorts limits clinical applicability and warrants future studies.

Conclusions

Elevated circulating sphingolipids were associated with AR, TP53, RB1, PI3K and AVPC aberrations in mCRPC, and the combination of lipid and genetic abnormalities conferred a worse prognosis. These findings suggest that certain genotypes in mCRPC may benefit from metabolic therapies.
Social accountability and health systems’ change, beyond the shock of Covid-19: drawing on histories of technical and activist approaches to rethink a shared code of practice
Authors: Nelson Erica , Waiswa Peter , Coelho Vera Schattan , Sarriot Eric
Published: March 2022

Background

Recognition of the value of “social accountability” to improve health systems performance and to address health inequities, has increased over the last decades, with different schools of thought engaging in robust dialogue. This article explores the tensions between health policy and systems research and practice on the one hand, and health equity-focussed activism on the other, as distinct yet interacting processes that have both been impacted by the shock effects of the Covid-19 pandemic. This extended commentary brings multidisciplinary voices seeking to look back at health systems history and fundamental social-institutional systems’ behaviors in order to contextualize these current debates over how best to push social accountability efforts forward.

Analysis

There is a documented history of tension between long and short processes of international health cooperation and intervention. Social accountability approaches, as a more recent strategy to improve health systems performance, intersect with this overarching history of negotiation between differently situated actors both global and local on whether to pursue sustained, slow, often community-driven change or to focus on rapid, measurable, often top-down interventions. Covid-19, as a global public health emergency, resulted in calls for urgent action which have unsurprisingly displaced some of the energy and aspiration for systemic transformation processes. A combination of accountability approaches and mechanisms have their own legitimacy in fostering health systems change, demanding collaboration between those that move both fast and slow, top-down and bottom-up.

Conclusion

We argue that social accountability, much like all efforts to strengthen health systems, is “everybody’s business” and that we must understand better the historical processes that have shaped the field of practice over time to move forward. These differences of perspective, knowledge-base and positioning vis-a-vis interventions or longer-term political commitment should not drive a conflict of legitimacy but instead be named, subsequently enabling the development of a shared code of conduct that applies to the breadth of actors involved in social accountability work. If we are concerned about the state of/status of social accountability within the context of “building back better” we must approach collaboration with a willingness to create dialogue across distinct disciplinary, technical and politically-informed ways of working.
Omega-3 fatty acids coordinate glucose and lipid metabolism in diabetic patients
Authors: Mone Pasquale , Varzideh Fahimeh , Kansakar Urna , Infante Carmine , Lombardi Angela , de Donato Antonio , Frullone Salvatore , Santulli Gaetano
Published: March 2022

Omega 3 polyunsaturated fatty acids (n-3 PUFA) are known to have beneficial effects on cardiovascular and metabolic health. However, whether different sources of n-3 PUFA, for instance fatty fish vs vegetable oils, could elicit different effects on glucose and lipid metabolism, remains to be determined. Herein we examine recent findings showing that while a plant-based n-3 PUFA supplementation for six months can reduce fasting blood glucose, marine-based n-3 PUFA can instead reduce serum levels of triglycerides. We also discuss the potential molecular mechanisms that could underlie these different effects on the regulation of glycolipid metabolism.
Cardiac assessment accuracy by students using palm-held ultrasound compared to physical examination by skilled cardiologists: a pilot study with a single medical student
Authors: Sarig Shirley , Or Tsafrir , Moady Gassan , Atar Shaul
Published: March 2022

Background

Despite the inherent limitations of the traditional cardiac physical examination (PE), it has not yet been replaced by a more accurate method.

Methods

We hypothesized that a single medical student, following a brief training (two academic hours) with the PHU, will better identify abnormal findings including significant valvular diseases, pericardial effusion and reduced LV function, as compared to PE performed by senior cardiologists and cardiology fellows. Transthoracic echocardiogram (TTE) served as a ‘gold standard’.

Results

Seventy-seven patients underwent TTE, of them 64 had an abnormal finding. PE identified 34 patients with an abnormal finding compared to 52 identified by PHU (p < 0.05). Ejection fraction (EF) below 50% was found in 35 patients on TTE, compared to only 15 and 6 patients by PE and PHU, respectively (p < 0.05). There was no difference in valvular dysfunction diagnosis detected by PE and medical students using PHU. The overall accuracy of PHU compared to TTE was 87%, with a specificity of 94% and sensitivity of 64% (the low sensitivity was driven mainly by EF assessment), whereas the accuracy of PE was 91%, specificity 91% and sensitivity 38% (again driven by poor EF assessment).

Conclusions

Cardiac evaluation using PHU by a single medical student was able to demonstrate similar accuracy as PE done by cardiac specialists or cardiology fellows. The study topic should be validated in future studies with more medical students with a very brief training of cardiac ultrasound.
Nanocarrier cancer therapeutics with functional stimuli-responsive mechanisms
Authors: Kaushik Neha , Borkar Shweta B. , Nandanwar Sondavid K. , Panda Pritam Kumar , Choi Eun Ha , Kaushik Nagendra Kumar
Published: March 2022

Presently, nanocarriers (NCs) have gained huge attention for their structural ability, good biocompatibility, and biodegradability. The development of effective NCs with stimuli-responsive properties has acquired a huge interest among scientists. When developing drug delivery NCs, the fundamental goal is to tackle the delivery-related problems associated with standard chemotherapy and to carry medicines to the intended sites of action while avoiding undesirable side effects. These nanocarriers were able of delivering drugs to tumors through regulating their pH, temperature, enzyme responsiveness. With the use of nanocarriers, chemotherapeutic drugs could be supplied to tumors more accurately that can equally encapsulate and deliver them. Material carriers for chemotherapeutic medicines are discussed in this review keeping in viewpoint of the structural properties and targeting methods that make these carriers more therapeutically effective, in addition to metabolic pathways triggered by drug-loaded NCs. Largely, the development of NCs countering to endogenous and exogenous stimuli in tumor regions and understanding of mechanisms would encourage the progress for tumor therapy and precision diagnosis in future.

Graphical Abstract
Clinical benefits of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer: a systematic review and meta-analysis
Authors: Zhang Xiao , Yang Zhengyang , An Yongbo , Liu Yishan , Wei Qi , Xu Fengming , Yao Hongwei , Zhang Zhongtao
Published: March 2022

Background

Immunotherapy for colorectal cancer has developed rapidly in the past decade. Many high-quality clinical trials examining the application of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer (mCRC) have been conducted in recent years. However, the clinical benefits, including the efficacy and safety of these treatments against mCRC, remain controversial. Hence, we conducted this meta-analysis on the clinical benefits of PD-1/PD-L1 inhibitors in patients with mCRC.

Methods

We searched online databases including MEDLINE, Embase, Cochrane Library, and Web of Science, from inception to January 4, 2021. The outcomes related to efficacy and safety were extracted and analyzed. Subgroup analyses were conducted according to the categories of dMMR-MSI-H (tumors with mismatch repair deficiency and high levels of microsatellite instability) ≥ 5% vs. dMMR-MSI-H < 5%, monotherapy vs. combination therapy, PD-1 inhibitors vs. PD-L1 inhibitors, and nivolumab vs. pembrolizumab.

Results

Fourteen studies including 1129 subjects were included in our systematic review. The overall complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD) rates were 0.01 (95% CI 0.00–0.04), 0.04 (95% CI 0.05–0.26), 0.27 (95% CI 0.22–0.32), and 0.44 (95% CI 0.30–0.58), respectively. The overall objective response rate (ORR) and disease control rate (DCR) were 0.16 (95%CI 0.06–0.31) and 0.50 (95%CI 0.35–0.65), respectively. The overall rate of adverse events (AEs) and severe adverse responses (SAEs) were 0.84 (95% CI 0.72–0.92) and 0.30 (95% CI 0.20–0.41), respectively. The ORRs of the dMMR-MSI-H ≥ 5% and dMMR-MSI-H < 5% subgroups were 0.40 (95% CI 0.30–0.51) and 0.04 (95% CI 0.00–0.09), respectively.

Conclusions

PD-1/PD-L1 inhibitors produced encouraging clinical benefits including the response rate in the treatment of dMMR-MSI-H mCRC. They actually have been influenced by the present state of mCRC therapy including pMMR-MSI-L mCRC. Nevertheless, additional multi-center prospective studies are still expected.

Trial registration

We have registered this study in the International Prospective Register of Systematic Reviews (PROSPERO), and the registration number is CRD42021249601.
Effect of artificial cycle with or without GnRH-a pretreatment on pregnancy and neonatal outcomes in women with PCOS after frozen embryo transfer: a propensity score matching study
Authors: Wang Yue , Hu Wen-Hui , Wan Qi , Li Tian , Qian Yue , Chen Ming-Xing , Tang Xiao-Jun , Feng Qian , Meng Xiang-Qian , Adu-Gyamfi Enoch Appiah , Ding Yu-Bin , Geng Li-Hong , Lv Xing-Yu , Zhong Zhao-Hui
Published: March 2022

Background

In frozen embryo transfer (FET), there is limited consensus on the best means of endometrial preparation in terms of the reproductive outcomes in women with polycystic ovary syndrome (PCOS). The present study aimed to compare the pregnancy and neonatal outcomes following artificial cycle FET (AC-FET) with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment among women with PCOS.

Methods

A total of 4503 FET cycles that satisfied the inclusion criteria were enrolled in this retrospective cohort study between 2015 and 2020. The GnRH-a group received GnRH-a pretreatment while the AC-FET group did not. Propensity score matching (PSM) method and multivariate logistic regression analysis were performed to adjust for potential confounding factors.

Results

After PSM, women in the GnRH-a group suffered a significantly lower miscarriage rate (11.2% vs. 17.1%, P = 0.033) and a higher live birth rate (LBR) compared with those in the AC-FET group (63.1% vs. 56.8%, P = 0.043). No differences were observed in the rates of biochemical pregnancy, clinical pregnancy and ectopic pregnancy between the two groups. A higher mean gestational age at birth was observed in the GnRH-a group than in the AC-FET group (39.80 ± 2.01 vs. 38.17 ± 2.13, P = 0.009). The incidence of neonatal preterm birth (PTB) in the GnRH-a group was lower than that in the AC-FET group (7.4% vs. 14.9%, P = 0.009). Singleton newborns conceived after GnRH-a group were more likely to be small for gestational age (SGA) than those born after AC-FET group (16.4% vs. 6.8%, P = 0.009). However, no significant differences were found between the two groups in terms of mean birthweight, apgar score, the rates of macrosomia, large for gestational age and low birth weight.

Conclusion(s)

In women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with a higher live birth rate and a reduced risk of neonatal PTB. However, there was a concomitant increase in the risk of developing SGA babies.
Estrogen inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia/reperfusion injury in rats by upregulating SERCA2a
Authors: Chen Jingwen , Liu Yang , Pan Defeng , Xu Tongda , Luo Yuanyuan , Wu Wanling , Wu Pei , Zhu Hong , Li Dongye
Published: March 2022

Background

The incidence of coronary heart disease (CHD) in premenopausal women is significantly lower than that of men of the same age, suggesting protective roles of estrogen for the cardiovascular system against CHD. This study aimed to confirm the protective effect of estrogen on myocardium during myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanisms.

Methods

Neonatal rat cardiomyocytes and Sprague–Dawley rats were used in this study. Different groups were treated by bilateral ovariectomy, 17β-estradiol (E2), adenoviral infection, or siRNA transfection. The expression of sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) and endoplasmic reticulum (ER) stress-related proteins were measured in each group to examine the effect of different E2 levels and determine the relationship between SERCA2a and ER stress. The cell apoptosis, myocardial infarction size, levels of apoptosis and serum cardiac troponin I, ejection fraction, calcium transient, and morphology changes of the myocardium and ER were examined to verify the effects of E2 on the myocardium.

Results

Bilateral ovariectomy resulted in reduced SERCA2a levels and more severe MI/R injury. E2 treatment increased SERCA2a expression. Both E2 treatment and exogenous SERCA2a overexpression decreased levels of ER stress-related proteins and alleviated myocardial damage. In contrast, SERCA2a knockdown exacerbated ER stress and myocardial damage. Addition of E2 after SERCA2a knockdown did not effectively inhibit ER stress or reduce myocardial injury.

Conclusions

Our data demonstrate that estrogen inhibits ER stress and attenuates MI/R injury by upregulating SERCA2a. These results provide a new potential target for therapeutic intervention and drug discovery in CHD.
Mind your step: Target walking task reveals gait disturbance in individuals with incomplete spinal cord injury
Authors: Mohammadzada Freschta , Zipser Carl Moritz , Easthope Chris A. , Halliday David M. , Conway Bernard A. , Curt Armin , Schubert Martin
Published: March 2022

Background

Walking over obstacles requires precise foot placement while maintaining balance control of the center of mass (CoM) and the flexibility to adapt the gait patterns. Most individuals with incomplete spinal cord injury (iSCI) are capable of overground walking on level ground; however, gait stability and adaptation may be compromised. CoM control was investigated during a challenging target walking (TW) task in individuals with iSCI compared to healthy controls. The hypothesis was that individuals with iSCI, when challenged with TW, show a lack of gait pattern adaptability which is reflected by an impaired adaptation of CoM movement compared to healthy controls.

Methods

A single-center controlled diagnostic clinical trial with thirteen participants with iSCI (0.3–24 years post injury; one subacute and twelve chronic) and twelve healthy controls was conducted where foot and pelvis kinematics were acquired during two conditions: normal treadmill walking (NW) and visually guided target walking (TW) with handrail support, during which participants stepped onto projected virtual targets synchronized with the moving treadmill surface. Approximated CoM was calculated from pelvis markers and used to calculate CoM trajectory length and mean CoM Euclidean distance TW-NW (primary outcome). Nonparametric statistics, including spearman rank correlations, were performed to evaluate the relationship between clinical parameter, outdoor mobility score, performance, and CoM parameters (secondary outcome).

Results

Healthy controls adapted to TW by decreasing anterior–posterior and vertical CoM trajectory length (p < 0.001), whereas participants with iSCI reduced CoM trajectory length only in the vertical direction (p = 0.002). Mean CoM Euclidean distance TW-NW correlated with participants’ neurological level of injury (R = 0.76, p = 0.002) and CoM trajectory length (during TW) correlated with outdoor mobility score (R = − 0.64, p = 0.026).

Conclusions

This study demonstrated that reduction of CoM movement is a common strategy to cope with TW challenge in controls, but it is impaired in individuals with iSCI. In the iSCI group, the ability to cope with gait challenges worsened the more rostral the level of injury. Thus, the TW task could be used as a gait challenge paradigm in ambulatory iSCI individuals.

Trial registration Registry number/ ClinicalTrials.gov Identifier: NCT03343132, date of registration 2017/11/17.