bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary Evidence of Children’s Weight Gain From 5 Months of Home Quarantine During the COVID-19 Pandemic
Authors: Brazendale Keith , Garcia Jeanette , Hunt Ethan T. , Blankenship Michael , Eisenstein Daniel , Leon Ana
Published: April 2021

Purpose. Preventive measures to curtail the spread of the Coronavirus Disease 2019 (COVID-19)—such as home quarantine, closure of schools/programs—are necessary, yet the impact of these restrictions on children’s weight status is unknown. The purpose of this case report was to investigate changes in children’s body mass index (BMI) and zBMI during COVID-19 quarantine. Methods. Children had their heights and weights recorded early March 2020 (pre-COVID-19) and 5 months later (early August 2020). Paired sample t tests examined changes in BMI and zBMI from baseline to follow-up. Results. Twenty-nine children (62% female; mean age 9.3 years; 27.5% with overweight or obesity) provided height and weight data at both time points. There was a significant difference in pre-COVID-19 BMI (mean [M] = 20.1, standard deviation [SD] = 6.0) and follow-up BMI (M = 20.7, SD = 6.4); t(57) = −3.8, P < .001, and pre-COVID-19 zBMI (M = 0.8, SD = 0.9) and follow-up zBMI (M = 0.9, SD = 0.9); t(57) = -3.1, P = .003. Five of the 29 children moved from normal weight to overweight (n = 4) or obese (n = 1) during 5 months of quarantine. Conclusions. Preliminary evidence shows most children increased their BMI and zBMI values from pre-COVID-19 assessment to the follow-up assessment, 5 months later. These initial findings identify potential incidental negative health consequences of children as a result of COVID-19 preventative measures such as home quarantine.
The Sacred and Profane of Japan’s Nuclear Safety Myth: On the Cultural Logic of Framing and Overflowing
Authors: Saito Hiro
Published: April 2021

Any policy requires a ‘frame’ and, by the same token, entails an ‘overflow’, externalizing a certain part of the world as irrelevant. This mundane business of policy framing and overflowing became an urgent matter of concern in Japan in March 2011, as the Fukushima nuclear disaster exposed how the existing frame of nuclear safety had permitted the fatal overflow of severe accident management. In fact, despite the creation of the new regulatory agency in September 2012, the post-Fukushima frame of nuclear safety continued to externalize off-site evacuation planning – a key component of severe accident management – until March 2015. To explain such persistence of the overflow, I borrow the concept of ‘sociotechnical imaginary’ from the policy-oriented strand of science and technology studies and infuse it with hermeneutical rigor of the strong program of cultural sociology. Specifically, I illustrate how the trajectory of Japan’s nuclear safety was decisively shaped by the pacifist imaginary and the safety myth, organized around the binary opposition ‘sacred = civilian use = safe vs. profane = military use = dangerous’, without reducing this deeper cultural logic of framing and overflowing to the political economy of nuclear energy or the global isomorphism of nuclear technology.
Efficacy and safety of neoadjuvant therapy for HER2-positive early breast cancer: a network meta-analysis
Authors: Zhang Jie , Yu Yushuai , Lin Yuxiang , Kang Shaohong , Lv Xinyin , Liu Yushan , Lin Jielong , Wang Jun , Song Chuangui
Published: April 2021

Aims:

Currently, there are many approaches available for neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer that improve therapeutic efficacy but are also controversial. We conducted a two-step Bayesian network meta-analysis (NMA) to compare odds ratios (ORs) for pathologic complete response (PCR) and safety endpoints.

Methods:

The Cochrane Central Register of Controlled Trials, PubMed, Embase, and online abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched comprehensively and systematically. Phase II/III randomised clinical trials for targeted therapy in at least one arm were included.

Results:

A total of 9779 published manuscripts were identified, and 36 studies including 10,379 patients were finally included in our analysis. The NMA of PCR showed that dual-target therapy is better than single-target therapy and combination chemotherapy is better than monochemotherapy. However, anthracycline did not bring extra benefits, whether combined with dual-target therapy or single-target therapy. On the other hand, the addition of endocrine therapy in the HER2-positive, hormone receptor (HR)-positive subgroup might have additional beneficial effects but without significant statistical difference. By performing a conjoint analysis of the PCR rate and safety endpoints, we found that ‘trastuzumab plus pertuzumab’ and ‘T-DM1 containing regimens’ were well balanced in terms of efficacy and toxicity in all target regimens.

Conclusion:

In summary, trastuzumab plus pertuzumab-based dual-target therapy with combination chemotherapy regimens showed the highest efficacy of all optional regimens. They also achieved the best balance between efficacy and toxicity. As our study showed that anthracycline could be replaced by carboplatin, we strongly recommended TCbHP as the preferred choice for neoadjuvant treatment of HER2-positive breast cancer. We also look forward to the potential value of T-DM1 in improving outcomes, which needs further study in future trials.
Oncogenic mechanism-based pharmaceutical validation of therapeutics targeting MET receptor tyrosine kinase
Authors: Yao Hang-Ping , Tong Xiang-Min , Wang Ming-Hai
Published: April 2021

Aberrant expression and/or activation of the MET receptor tyrosine kinase is characterized by genomic recombination, gene amplification, activating mutation, alternative exon-splicing, increased transcription, and their different combinations. These dysregulations serve as oncogenic determinants contributing to cancerous initiation, progression, malignancy, and stemness. Moreover, integration of the MET pathway into the cellular signaling network as an addiction mechanism for survival has made this receptor an attractive pharmaceutical target for oncological intervention. For the last 20 years, MET-targeting small-molecule kinase inhibitors (SMKIs), conventional therapeutic monoclonal antibodies (TMABs), and antibody-based biotherapeutics such as bispecific antibodies, antibody–drug conjugates (ADC), and dual-targeting ADCs have been under intensive investigation. Outcomes from preclinical studies and clinical trials are mixed with certain successes but also various setbacks. Due to the complex nature of MET dysregulation with multiple facets and underlying mechanisms, mechanism-based validation of MET-targeting therapeutics is crucial for the selection and validation of lead candidates for clinical trials. In this review, we discuss the importance of various types of mechanism-based pharmaceutical models in evaluation of different types of MET-targeting therapeutics. The advantages and disadvantages of these mechanism-based strategies for SMKIs, conventional TMABs, and antibody-based biotherapeutics are analyzed. The demand for establishing new strategies suitable for validating novel biotherapeutics is also discussed. The information summarized should provide a pharmaceutical guideline for selection and validation of MET-targeting therapeutics for clinical application in the future.
Discursive stickiness: Affective institutional texts and activist resistance
Authors: Ciszek Erica , Mocarski Richard , Price Sarah , Almeida Elaine
Published: April 2021

Pushing the bounds of public relations theory and research, we explore how institutional texts have produced and reified stigmas around gender transgression and how these texts are bound up in moments of activism and resistance. We considered how different discursive and material functions get “stuck” together by way of texts and how this sticking depends on a history of association and institutionalization. Activism presents opportunities to challenge institutional and structural stickiness, and we argue that public relations can challenge the affective assemblages that comprise and perpetuate these systems, unsettling the historical discourses that have governed institutions by establishing new communicative possibilities.
Inadequate Measles, Mumps, Rubella, and Varicella Immunity Among Employees
Authors: Ezeji-Okoye Stephen , Bilodeau Brittney L. , Madhusudhan Divya K. , Pruett Eileen , Thokala Sujith , Bravata Dena M.
Published: April 2021

Objectives:

The purpose of this cohort study was to evaluate measles, mumps, rubella (MMR), and varicella immunity among a population of adult employees receiving primary care in an employer-sponsored health center.

Methods:

Participants were eligible for MMR and varicella immunity screening if they were an employee receiving primary care in an employer-sponsored health center between January 1, 2019 and November 1, 2020 who could not provide proof of immunization and 1) had it recommended by their provider, 2) specifically requested immunity testing (often because they had heard of measles outbreaks in their country of origin), or 3) were seen for an immigration physical for their Green Card application.

Results:

Overall, 3494 patients were screened for their MMR immunity. Of these, 3057 were also screened for varicella immunity. Among these patients, 13.9% lacked measles immunity, 0.83% lacked immunity to all 3 components of MMR, and 13.2% lacked varicella immunity. Among the 262 patients who presented specifically for immunity screening, the rates of lacking immunity were higher for all conditions: 22.7% lacked measles immunity and 9.2% lacked varicella immunity.

Conclusion:

Given declines in immunizations during the COVID-19 pandemic, there is reason to be concerned that measles and varicella-associated morbidity and mortality may rise. Employers, especially those with large foreign-born populations or who require international travel may want to educate their populations about common contagious illnesses and offer immunity validation or vaccinations at no or low cost.
Considering Needle Phobia among Adult Patients During Mass COVID-19 Vaccinations
Authors: Love Ashley S. , Love Robert J.
Published: April 2021

As mass vaccination is underway to combat the COVID-19 pandemic and achieve herd immunity, healthcare professionals need to recognize the fear and phobia of needles among their patients. Approximately 11.5 to 66 million U.S. adults may suffer from this condition. This population often avoids seeking medical care including vaccinations. The exact number of people suffering from this phobia is unknown, and the potential years of life lost in the American health care system cannot be estimated accurately. The resistance to vaccinations among this population may delay achieving herd immunity to end this current pandemic. An overview of needle phobia, vaccinations, and current treatments are explored. The use of telemedicine could prove critical for reaching this population as well as those who are hesitant about vaccinations. Providing education to healthcare providers to identify and manage these patients during the pandemic is necessary.
Identification of the molecular regulation of differences in lipid deposition in dedifferentiated preadipocytes from different chicken tissues
Authors: Ma Zheng , Luo Na , Liu Lu , Cui Huanxian , Li Jing , Xiang Hai , Kang Huimin , Li Hua , Zhao Guiping
Published: April 2021

Background

A body distribution with high intramuscular fat and low abdominal fat is the ideal goal for broiler breeding. Preadipocytes with different origins have differences in terms of metabolism and gene expression. The transcriptome analysis performed in this study of intramuscular preadipocytes (DIMFPs) and adipose tissue-derived preadipocytes (DAFPs) aimed to explore the characteristics of lipid deposition in different chicken preadipocytes by dedifferentiation in vitro.

Results

Compared with DAFPs, the total lipid content in DIMFPs was reduced (P < 0.05). Moreover, 72 DEGs related to lipid metabolism were screened, which were involved in adipocyte differentiation, fatty acid transport and fatty acid synthesis, lipid stabilization, and lipolysis. Among the 72 DEGs, 19 DEGs were enriched in the PPAR signaling pathway, indicating its main contribution to the regulation of the difference in lipid deposition between DAFPs and DIMFPs. Among these 19 genes, the representative APOA1, ADIPOQ, FABP3, FABP4, FABP7, HMGCS2, LPL and RXRG genes were downregulated, but the ACSL1, FABP5, PCK2, PDPK1, PPARG, SCD, SCD5, and SLC27A6 genes were upregulated (P < 0.05 or P < 0.01) in the DIMFPs. In addition, the well-known pathways affecting lipid metabolism (MAPK, TGF-beta and calcium) and the pathways related to cell communication were enriched, which may also contribute to the regulation of lipid deposition. Finally, the regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs was proposed based on the above information.

Conclusions

Our data suggested a difference in lipid deposition between DIMFPs and DAFPs of chickens in vitro and proposed a molecular regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs. The lipid content was significantly increased in DAFPs by the direct mediation of PPAR signaling pathways. These findings provide new insights into the regulation of tissue-specific fat deposition and the optimization of body fat distribution in broilers.
Type I error control for cluster randomized trials under varying small sample structures
Authors: Nugent Joshua R. , Kleinman Ken P.
Published: April 2021

Background

Linear mixed models (LMM) are a common approach to analyzing data from cluster randomized trials (CRTs). Inference on parameters can be performed via Wald tests or likelihood ratio tests (LRT), but both approaches may give incorrect Type I error rates in common finite sample settings. The impact of different combinations of cluster size, number of clusters, intraclass correlation coefficient (ICC), and analysis approach on Type I error rates has not been well studied. Reviews of published CRTs find that small sample sizes are not uncommon, so the performance of different inferential approaches in these settings can guide data analysts to the best choices.

Methods

Using a random-intercept LMM stucture, we use simulations to study Type I error rates with the LRT and Wald test with different degrees of freedom (DF) choices across different combinations of cluster size, number of clusters, and ICC.

Results

Our simulations show that the LRT can be anti-conservative when the ICC is large and the number of clusters is small, with the effect most pronouced when the cluster size is relatively large. Wald tests with the between-within DF method or the Satterthwaite DF approximation maintain Type I error control at the stated level, though they are conservative when the number of clusters, the cluster size, and the ICC are small.

Conclusions

Depending on the structure of the CRT, analysts should choose a hypothesis testing approach that will maintain the appropriate Type I error rate for their data. Wald tests with the Satterthwaite DF approximation work well in many circumstances, but in other cases the LRT may have Type I error rates closer to the nominal level.
Deep generative models in DataSHIELD
Authors: Lenz Stefan , Hess Moritz , Binder Harald
Published: April 2021

Background

The best way to calculate statistics from medical data is to use the data of individual patients. In some settings, this data is difficult to obtain due to privacy restrictions. In Germany, for example, it is not possible to pool routine data from different hospitals for research purposes without the consent of the patients.

Methods

The DataSHIELD software provides an infrastructure and a set of statistical methods for joint, privacy-preserving analyses of distributed data. The contained algorithms are reformulated to work with aggregated data from the participating sites instead of the individual data. If a desired algorithm is not implemented in DataSHIELD or cannot be reformulated in such a way, using artificial data is an alternative. Generating artificial data is possible using so-called generative models, which are able to capture the distribution of given data. Here, we employ deep Boltzmann machines (DBMs) as generative models. For the implementation, we use the package “BoltzmannMachines” from the Julia programming language and wrap it for use with DataSHIELD, which is based on R.

Results

We present a methodology together with a software implementation that builds on DataSHIELD to create artificial data that preserve complex patterns from distributed individual patient data. Such data sets of artificial patients, which are not linked to real patients, can then be used for joint analyses. As an exemplary application, we conduct a distributed analysis with DBMs on a synthetic data set, which simulates genetic variant data. Patterns from the original data can be recovered in the artificial data using hierarchical clustering of the virtual patients, demonstrating the feasibility of the approach. Additionally, we compare DBMs, variational autoencoders, generative adversarial networks, and multivariate imputation as generative approaches by assessing the utility and disclosure of synthetic data generated from real genetic variant data in a distributed setting with data of a small sample size.

Conclusions

Our implementation adds to DataSHIELD the ability to generate artificial data that can be used for various analyses, e.g., for pattern recognition with deep learning. This also demonstrates more generally how DataSHIELD can be flexibly extended with advanced algorithms from languages other than R.
Predictors of the one-year-change in depressiveness in informal caregivers of community-dwelling people with dementia
Authors: Kürten Lara , Dietzel Nikolas , Kolominsky-Rabas Peter L. , Graessel Elmar
Published: April 2021

Background

The care of people with dementia is usually carried out by their family members, which can cause objective und subjective burden and raise their risk of depressiveness. Thus, the aim of this study is to identify predictors of the change in depressiveness of informal caregivers over 1 year in order to be able to derive hypotheses for interventions that promise success.

Methods

The Bavarian Dementia Survey (BayDem) is a multi-center, longitudinal study conducted at three different sites in Bavaria, Germany. Participants were people with dementia and their informal caregivers. Data was collected at baseline and after 12 months by standardized face-to-face interviews in cooperation with local players. The informal caregivers’ depressiveness was assessed with the WHO-5. Data was also collected on the people with dementia’s cognition (MMSE), behavioral symptoms (NPI) and comorbidities (Charlson Comorbidity Index) as well as caregivers’ social inclusion (LSNS), time spent on care and care contribution (RUD). For statistical analysis, a multiple regression model was used.

Results

The data of 166 people with dementia and their informal caregivers was analyzed. Of the latter, 46% were categorized as “likely depressed”. The change in depressiveness over a year was significantly predicted by baseline depressiveness as well as an increase in the time informal caregivers spent supervising the person with dementia.

Conclusions

Informal caregivers of people with dementia are at high risk of depression. The time spent supervising the person with dementia has a significant impact on increasing depressiveness. This highlights the importance of support services to provide the informal caregiver with relief and possibly reduce depressiveness.
‘Too old to test?’: A life course approach to HIV-related risk and self-testing among midlife-older adults in Malawi
Authors: Johnson Cheryl , Kumwenda Moses , Meghji Jamilah , Choko Augustine T. , Phiri Mackwellings , Hatzold Karin , Baggaley Rachel , Taegtmeyer Miriam , Terris-Prestholt Fern , Desmond Nicola , Corbett Elizabeth L.
Published: April 2021

Background

Despite the aging HIV epidemic, increasing age can be associated with hesitancy to test. Addressing this gap is a critical policy concern and highlights the urgent need to identify the underlying factors, to improve knowledge of HIV-related risks as well as uptake of HIV testing and prevention services, in midlife-older adults.

Methods

We conducted five focus group discussions and 12 in-depth interviews between April 2013 and November 2016 among rural and urban Malawian midlife-older (≥30 years) men and women. Using a life-course theoretical framework we explored how age is enacted socially and its implications on HIV testing and sexual risk behaviours. We also explore the potential for HIV self-testing (HIVST) to be part of a broader strategy for engaging midlife-older adults in HIV testing, prevention and care. Thematic analysis was used to identify recurrent themes and variations.

Results

Midlife-older adults (30–74 years of age) associated their age with respectability and identified HIV as “a disease of youth” that would not affect them, with age protecting them against infidelity and sexual risk-taking. HIV testing was felt to be stigmatizing, challenging age norms, threatening social status, and implying “lack of wisdom”. These norms drove self-testing preferences at home or other locations deemed age and gender appropriate. Awareness of the potential for long-standing undiagnosed HIV to be carried forward from past relationships was minimal, as was understanding of treatment-as-prevention. These norms led to HIV testing being perceived as a threat to status by older adults, contributing to low levels of recent HIV testing compared to younger adults.

Conclusions

Characteristics associated with age-gender norms and social position encourage self-testing but drive poor HIV-risk perception and unacceptability of conventional HIV testing in midlife-older adults. There is an urgent need to provide targeted messages and services more appropriate to midlife-older adults in sub-Saharan Africa. HIVST which has often been highlighted as a tool for reaching young people, may be a valuable tool for engaging midlife-older age groups who may not otherwise test.
Changes in the characteristics of dental emergencies under the influence of SARS-CoV-2 pandemic: a retrospective study
Authors: Wu Kan , Li Chunjie , Yang Zheng , Yang Shangchun , Yang Wenbing , Hua Chengge
Published: April 2021

Background

Further understanding of the distribution and changing characteristics of dental diseases is of great significance for all dental emergency centers for strengthening the medical staff’s treatment knowledge abilities and effective use of emergency resources in the face of public health emergencies involving highly infectious respiratory diseases.

Methods

The medical records of 4158 dental emergency patients in 2019 and 2020 were retrospectively analyzed and divided into pre-SARS-COV-2 group and SARS-COV-2 group according to time. The demographic data, date and time, diagnosis, and treatment methods of the two groups were statistically described, and the chi-squared test was used to analyze the differences. The medical records of 4158 dental emergency patients during the same period of two years in 2019 and 2020 were retrospectively analyzed and divided into SARS-COV-2 pre-group and SARS-COV-2 group according to time. The demographic data, date and time, diagnosis and treatment methods of the two groups were statistically described, and the chi-square test was used to determine the differences.

Results

During the SARS-COV-2 pandemic, the number of dental emergency visits increased by 29.7%. During the pandemic, males (n = 286, 58.1%) were more likely to visit dental emergency centers for trauma than females (n = 206, 41.9%) (P < 0.05); females (n = 242, 60.8%) were more likely to visit dental emergency centers for acute gingivitis and acute pericoronitis than males (n = 156, 39.2%) (P < 0.05). A major change in diagnosis was related to acute pulpitis (K04.0) and acute apical periodontitis (K04.4), which increased by 9.2%; acute gingivitis (K05.0) and acute pericoronitis (K05.2) increased by 3.5%; open wound of the lip and oral cavity (S01.5) decreased by 17.9%; other conditions (non-emergency diseases) increased by 6.8%, compared with the pre-SARS-COV-2 period. Among the treatment modalities, during the pre-SARS-COV-2 period, 304 patients (17.7%) received a prescription for antibiotics and analgesics, and 1485 (86.5%) received a prescription for local treatment. During the SARS-COV-2 period, 958 (39.2%) received a prescription for antibiotics and analgesics, and 1636 (67.0%) received a prescription for local treatment.

Conclusion

SARS-COV-2 pandemic led to changes in the characteristics of dental emergency patients. Trauma, acute pulpitis, and acute periodontitis are the leading reasons patients refer to dental emergency centers. Dental emergency centers should optimize treatment procedures, optimize the staff, and reasonably allocate materials according to the changes to improve the on-site treatment capacity and provide adequate dental emergency care.
Development and operation of a digital platform for sharing pathology image data
Authors: Kang Yunsook , Kim Yoo Jung , Park Seongkeun , Ro Gun , Hong Choyeon , Jang Hyungjoon , Cho Sungduk , Hong Won Jae , Kang Dong Un , Chun Jonghoon , Lee Kyoungbun , Kang Gyeong Hoon , Moon Kyoung Chul , Choe Gheeyoung , Lee Kyu Sang , Park Jeong Hwan , Jeong Won-Ki , Chun Se Young , Park Peom , Choi Jinwook
Published: April 2021

Background

Artificial intelligence (AI) research is highly dependent on the nature of the data available. With the steady increase of AI applications in the medical field, the demand for quality medical data is increasing significantly. We here describe the development of a platform for providing and sharing digital pathology data to AI researchers, and highlight challenges to overcome in operating a sustainable platform in conjunction with pathologists.

Methods

Over 3000 pathological slides from five organs (liver, colon, prostate, pancreas and biliary tract, and kidney) in histologically confirmed tumor cases by pathology departments at three hospitals were selected for the dataset. After digitalizing the slides, tumor areas were annotated and overlaid onto the images by pathologists as the ground truth for AI training. To reduce the pathologists’ workload, AI-assisted annotation was established in collaboration with university AI teams.

Results

A web-based data sharing platform was developed to share massive pathological image data in 2019. This platform includes 3100 images, and 5 pre-processing algorithms for AI researchers to easily load images into their learning models.

Discussion

Due to different regulations among countries for privacy protection, when releasing internationally shared learning platforms, it is considered to be most prudent to obtain consent from patients during data acquisition.

Conclusions

Despite limitations encountered during platform development and model training, the present medical image sharing platform can steadily fulfill the high demand of AI developers for quality data. This study is expected to help other researchers intending to generate similar platforms that are more effective and accessible in the future.
Development, validation, and proof-of-concept implementation of a two-year risk prediction model for undiagnosed atrial fibrillation using common electronic health data (UNAFIED)
Authors: Grout Randall W. , Hui Siu L. , Imler Timothy D. , El-Azab Sarah , Baker Jarod , Sands George H. , Ateya Mohammad , Pike Francis
Published: April 2021

Background

Many patients with atrial fibrillation (AF) remain undiagnosed despite availability of interventions to reduce stroke risk. Predictive models to date are limited by data requirements and theoretical usage. We aimed to develop a model for predicting the 2-year probability of AF diagnosis and implement it as proof-of-concept (POC) in a production electronic health record (EHR).

Methods

We used a nested case–control design using data from the Indiana Network for Patient Care. The development cohort came from 2016 to 2017 (outcome period) and 2014 to 2015 (baseline). A separate validation cohort used outcome and baseline periods shifted 2 years before respective development cohort times. Machine learning approaches were used to build predictive model. Patients ≥ 18 years, later restricted to age ≥ 40 years, with at least two encounters and no AF during baseline, were included. In the 6-week EHR prospective pilot, the model was silently implemented in the production system at a large safety-net urban hospital. Three new and two previous logistic regression models were evaluated using receiver-operating characteristics. Number, characteristics, and CHA2DS2-VASc scores of patients identified by the model in the pilot are presented.

Results

After restricting age to ≥ 40 years, 31,474 AF cases (mean age, 71.5 years; female 49%) and 22,078 controls (mean age, 59.5 years; female 61%) comprised the development cohort. A 10-variable model using age, acute heart disease, albumin, body mass index, chronic obstructive pulmonary disease, gender, heart failure, insurance, kidney disease, and shock yielded the best performance (C-statistic, 0.80 [95% CI 0.79–0.80]). The model performed well in the validation cohort (C-statistic, 0.81 [95% CI 0.8–0.81]). In the EHR pilot, 7916/22,272 (35.5%; mean age, 66 years; female 50%) were identified as higher risk for AF; 5582 (70%) had CHA2DS2-VASc score ≥ 2.

Conclusions

Using variables commonly available in the EHR, we created a predictive model to identify 2-year risk of developing AF in those previously without diagnosed AF. Successful POC implementation of the model in an EHR provided a practical strategy to identify patients who may benefit from interventions to reduce their stroke risk.
PAR-4/Ca2+-calpain pathway activation stimulates platelet-derived microparticles in hyperglycemic type 2 diabetes
Authors: Giannella Alessandra , Ceolotto Giulio , Radu Claudia Maria , Cattelan Arianna , Iori Elisabetta , Benetti Andrea , Fabris Fabrizio , Simioni Paolo , Avogaro Angelo , Vigili de Kreutzenberg Saula
Published: April 2021

Background

Patients with type 2 diabetes (T2DM) have a prothrombotic state that needs to be fully clarified; microparticles (MPs) have emerged as mediators and markers of this condition. Thus, we investigate, in vivo, in T2DM either with good (HbA1c ≤ 7.0%; GGC) or poor (HbA1c > 7.0%; PGC) glycemic control, the circulating levels of MPs, and in vitro, the molecular pathways involved in the release of MPs from platelets (PMP) and tested their pro-inflammatory effects on THP-1 transformed macrophages.

Methods

In 59 T2DM, and 23 control subjects with normal glucose tolerance (NGT), circulating levels of CD62E+, CD62P+, CD142+, CD45+ MPs were determined by flow cytometry, while plasma levels of ICAM-1, VCAM-1, IL-6 by ELISA. In vitro, PMP release and activation of isolated platelets from GGC and PGC were investigated, along with their effect on IL-6 secretion in THP-1 transformed macrophages.

Results

We found that MPs CD62P+ (PMP) and CD142+ (tissue factor-bearing MP) were significantly higher in PGC T2DM than GGC T2DM and NGT. Among MPs, PMP were also correlated with HbA1c and IL-6. In vitro, we showed that acute thrombin exposure stimulated a significantly higher PMP release in PGC T2DM than GGC T2DM through a more robust activation of PAR-4 receptor than PAR-1 receptor. Treatment with PAR-4 agonist induced an increased release of PMP in PGC with a Ca2+-calpain dependent mechanism since this effect was blunted by calpain inhibitor. Finally, the uptake of PMP derived from PAR-4 treated PGC platelets into THP-1 transformed macrophages promoted a marked increase of IL-6 release compared to PMP derived from GGC through the activation of the NF-kB pathway.

Conclusions

These results identify PAR-4 as a mediator of platelet activation, microparticle release, and inflammation, in poorly controlled T2DM.
Triglyceride–glucose index and the incidence of atherosclerotic cardiovascular diseases: a meta-analysis of cohort studies
Authors: Ding Xiaobo , Wang Xiaozhen , Wu Jing , Zhang Manli , Cui Meizi
Published: April 2021

Background

Insulin resistance has been demonstrated to be involved in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVDs). This study evaluated the association between the triglyceride–glucose (TyG) index, a novel surrogate indicator of insulin resistance, and the incidence of ASCVDs in people without ASCVDs at baseline by performing a meta-analysis.

Methods

Cohort studies reporting the multivariate-adjusted association between the TyG index and the incidence of ASCVDs were obtained by searching the PubMed and Embase databases. A random-effects model incorporating intra-study heterogeneity was applied to combine the results.

Results

Eight cohort studies comprising 5,731,294 participants were included in this meta-analysis. The results showed that compared to those with the lowest TyG index category, participants with the highest TyG index category were independently associated with a higher risk of ASCVDs [hazard ratio (HR): 1.61, 95% confidence interval (CI) 1.29–2.01, I2 = 80%, P < 0.001]. This finding was consistent with the meta-analysis results with the TyG index analyzed as a continuous variable (HR per 1-unit increment of the TyG index: 1.39, 95% CI 1.18–1.64, I2 = 89%, P < 0.001). Subgroup analyses suggested that the age, sex, and diabetic status did not significantly affect the association (for subgroup analyses, all P > 0.05). Moreover, participants with the highest TyG index category were independently associated with a higher risk of coronary artery disease [(CAD), HR: 1.95, 95% CI 1.47–2.58, I2 = 92%, P < 0.001] and stroke (HR: 1.26, 95% CI 1.23–1.29, I2 = 0%, P < 0.001).

Conclusions

A higher TyG index may be independently associated with a higher incidence of ASCVDs, CAD, and stroke in people without ASCVDs at baseline.
Age and sex are associated with the plasma lipidome: findings from the GOLDN study
Authors: Slade Emily , Irvin Marguerite R. , Xie Kevin , Arnett Donna K. , Claas Steven A. , Kind Tobias , Fardo David W. , Graf Gregory A.
Published: April 2021

Background

Developing an understanding of the biochemistry of aging in both sexes is critical for managing disease throughout the lifespan. Lipidomic associations with age and sex have been reported, but prior studies are limited by measurements in serum rather than plasma or by participants taking lipid-lowering medications.

Methods

Our study included lipidomic data from 980 participants aged 18–87 years old from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN). Participants were off lipid-lowering medications for at least 4 weeks, and signal intensities of 413 known lipid species were measured in plasma. We examined linear age and sex associations with signal intensity of (a) 413 lipid species; (b) 6 lipid classes (glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, fatty acids, and acylcarnitines); and (c) 15 lipid subclasses; as well as with the particle sizes of three lipoproteins.

Results

Significant age associations were identified in 4 classes, 11 subclasses, 147 species, and particle size of one lipoprotein while significant sex differences were identified in 5 classes, 12 subclasses, 248 species, and particle sizes of two lipoproteins. For many lipid species (n = 97), age-related associations were significantly different between males and females. Age*sex interaction effects were most prevalent among phosphatidylcholines, sphingomyelins, and triglycerides.

Conclusion

We identified several lipid species, subclasses, and classes that differ by age and sex; these lipid phenotypes may serve as useful biomarkers for lipid changes and associated cardiovascular risk with aging in the future. Future studies of age-related changes throughout the adult lifespan of both sexes are warranted.

Trial registration

ClinicalTrials.govNCT00083369; May 21, 2004.
Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion
Authors: Suzuki Kaoru , Shinohara Mitsuru , Uno Yoshihiro , Tashiro Yoshitaka , Gheni Ghupurjan , Yamamoto Miho , Fukumori Akio , Shindo Akihiko , Mashimo Tomoji , Tomimoto Hidekazu , Sato Naoyuki
Published: April 2021

Background

Subcortical ischemic vascular dementia, one of the major subtypes of vascular dementia, is characterized by lacunar infarcts and white matter lesions caused by chronic cerebral hypoperfusion. In this study, we used a mouse model of bilateral common carotid artery stenosis (BCAS) to investigate the role of B-cell translocation gene 2 (BTG2), an antiproliferation gene, in the white matter glial response to chronic cerebral hypoperfusion.

Methods

Btg2−/−mice and littermate wild-type control mice underwent BCAS or sham operation. Behavior phenotypes were assessed by open-field test and Morris water maze test. Brain tissues were analyzed for the degree of white matter lesions and glial changes. To further confirm the effects ofBtg2deletion on proliferation of glial cells in vitro, BrdU incorporation was investigated in mixed glial cells derived from wild-type andBtg2−/−mice.

Results

Relative to wild-type mice with or without BCAS, BCAS-treatedBtg2−/−mice exhibited elevated spontaneous locomotor activity and poorer spatial learning ability. Although the severities of white matter lesions did not significantly differ between wild-type andBtg2−/−mice after BCAS, the immunoreactivities of GFAP, a marker of astrocytes, and Mac2, a marker of activated microglia and macrophages, in the white matter of the optic tract were higher in BCAS-treatedBtg2−/−mice than in BCAS-treated wild-type mice. The expression level ofGfapwas also significantly elevated in BCAS-treatedBtg2−/−mice. In vitro analysis showed that BrdU incorporation in mixed glial cells in response to inflammatory stimulation associated with cerebral hypoperfusion was higher inBtg2−/−mice than in wild-type mice.

Conclusion

BTG2 negatively regulates glial cell proliferation in response to cerebral hypoperfusion, resulting in behavioral changes.
Barriers and drivers to stakeholder engagement in global mental health projects
Authors: Murphy Jill , Qureshi Onaiza , Endale Tarik , Esponda Georgina Miguel , Pathare Soumitra , Eaton Julian , De Silva Mary , Ryan Grace
Published: April 2021

Background

Engagement with diverse stakeholders, including policy makers, care providers and service users and communities, is essential for successful implementation of global mental health interventions. Despite being a fundamental factor in the implementation process, evidence about challenges and drivers to stakeholder engagement is limited in the global mental health literature.

Methods

We conducted semi-structured qualitative interviews with 29 recipients of Grand Challenges Canada Global Mental Health funding to assess barriers and drivers to global mental health implementation across a portfolio of projects. We used framework analysis to identify key themes related to implementation barriers and drivers. This paper reports on barriers and drivers to stakeholder engagement, with results related to capacity development and service delivery reported elsewhere in this journal.

Results

Barriers and drivers to stakeholder engagement were identified across four themes: (1) Contextual Considerations, (2) Resources, (3) Participation, Uptake and Empowerment, and (4) Stigma. While complex contextual challenges create barriers, mechanisms such as formative research can facilitate a deeper contextual understanding that supports effective implementation planning. Limited financial and human resources and competing priorities can lead to substantial challenges. Investing in and leveraging existing local resources and expertise can help to mitigate these barriers. The challenge of achieving active participation from stakeholders and diverging expectations about the nature of participation were identified as barriers, while providing opportunities for meaningful participation and empowerment acted as drivers. Stigma at the institutional, community and individual level was also identified as a substantial barrier to engagement.

Conclusion

The findings of this study are relevant to implementers in global mental health. They also have implications for global mental health funding agencies and policy organizations, who can support improved stakeholder engagement by investing in high-quality formative research, supporting capacity building for policy engagement, investing in longer-term funding schemes to support sustainable partnerships and scale-up, thus fostering successful engagement and supporting effective implementation of global mental health innovations.
Professional stakeholder’s views of adolescent weight management programmes: a qualitative study
Authors: Jones Helen M. , Oyebode Oyinlola , Melendez-Torres G. J. , Al-Khudairy Lena
Published: April 2021

Objective

Family-based multi-component weight management programmes are recommended for adolescents with obesity in England and Wales, however, these programmes suffer from poor uptake and high attrition rates. This study aimed to gather the views of professional stakeholders in a UK weight management programme to identify potential areas to target to improve engagement and success for such programmes.

Results

Semi-structured interviews were conducted with those involved in the commissioning, referral, coordination or delivery of a weight management programme (n = 11). Interviews were analysed using qualitative content analysis. Three main categories developed: professional support, tailoring and intervention content. Participants recognised the importance of support from experienced professionals, as well as family and peers. There was agreement that longer-term support was needed for adolescents with obesity; suggestions included integrating follow-up support with schools and leisure services. Emotional and psychological support must be prioritised. Having a variety of delivery modes, such as group and one to one, particularly in the home environment, were recommended. Stakeholders agreed that weight management programmes for adolescents need to be more proactive at incorporating technology. By acting on the views of those that work closely with adolescents, engagement with weight management programmes may be improved.
On the geophysical processes impacting palaeo-sea-level observations
Authors: Yokoyama Yusuke , Purcell Anthony
Published: April 2021

Past sea-level change represents the large-scale state of global climate, reflecting the waxing and waning of global ice sheets and the corresponding effect on ocean volume. Recent developments in sampling and analytical methods enable us to more precisely reconstruct past sea-level changes using geological indicators dated by radiometric methods. However, ice-volume changes alone cannot wholly account for these observations of local, relative sea-level change because of various geophysical factors including glacio-hydro-isostatic adjustments (GIA). The mechanisms behind GIA cannot be ignored when reconstructing global ice volume, yet they remain poorly understood within the general sea-level community. In this paper, various geophysical factors affecting sea-level observations are discussed and the details and impacts of these processes on estimates of past ice volumes are introduced.
Tunnel engineering for modulating the substrate preference in cytochrome P450BsβHI
Authors: Meng Shuaiqi , An Ruipeng , Li Zhongyu , Schwaneberg Ulrich , Ji Yu , Davari Mehdi D. , Wang Fang , Wang Meng , Qin Meng , Nie Kaili , Liu Luo
Published: April 2021

An active site is normally located inside enzymes, hence substrates should go through a tunnel to access the active site. Tunnel engineering is a powerful strategy for refining the catalytic properties of enzymes. Here, P450BsβHI (Q85H/V170I) derived from hydroxylase P450Bsβ from Bacillus subtilis was chosen as the study model, which is reported as a potential decarboxylase. However, this enzyme showed low decarboxylase activity towards long-chain fatty acids. Here, a tunnel engineering campaign was performed for modulating the substrate preference and improving the decarboxylation activity of P450BsβHI. The finally obtained BsβHI-F79A variant had a 15.2-fold improved conversion for palmitic acid; BsβHI-F173V variant had a 3.9-fold improved conversion for pentadecanoic acid. The study demonstrates how the substrate preference can be modulated by tunnel engineering strategy.
Biotransformation of soy whey into a novel functional beverage by Cordyceps militaris SN-18
Authors: Dai Yiqiang , Zhou Jianzhong , Wang Lixia , Dong Mingsheng , Xia Xiudong
Published: April 2021

Soy whey, a liquid nutritional by-product of soybean manufacture, is rich in proteins, oligosaccharides and isoflavones. Soy whey can be used to produce functional beverages, instead of discarding it as a waste. In this study, unfermented soy whey (USW) and Cordyceps militaris SN-18-fermented soy whey (FSW) were investigated and compared for their physicochemical and functional properties by high performance liquid chromatography (HPLC) and DNA damage assay. Results show that C. militaris SN-18 fermentation could increase the contents of essential amino acids, total phenolic and flavonoid and isoflavone aglycones and eliminate the oligosaccharides in soy whey. Furthermore, C. militaris SN-18 could significantly enhance the ABTS radical scavenging ability, reducing power and ferric reducing power of soy whey, and its fermented products could prominently attenuate Fenton reaction-induced DNA damage. These findings indicate that soy whey can potentially be converted into a novel soy functional beverage by C. militaris SN-18 fermentation.

Graphical abstract
Challenges in shallow target reconstruction by 3D elastic full-waveform inversion — Which initial model?
Authors: Teodor Daniela , Comina Cesare , Khosro Anjom Farbod , Brossier Romain , Valentina Socco Laura , Virieux Jean
Published: April 2021

Elastic full-waveform inversion (FWI) is a powerful tool for high-resolution subsurface multiparameter characterization. However, 3D FWI applied to land data for near-surface applications is particularly challenging because the seismograms are dominated by highly energetic, dispersive, and complex-scattered surface waves (SWs). In these conditions, a successful deterministic FWI scheme requires an accurate initial model. Our study, primarily focused on field data analysis for 3D applications, aims at enhancing the resolution in the imaging of complex shallow targets, by integrating devoted SW analysis techniques with a 3D spectral-element-based elastic FWI. From dispersion curves, extracted from seismic data recorded over a sharp-interface shallow target, we build different initial S-wave ([Formula: see text]) and P-wave ([Formula: see text]) velocity models (laterally homogeneous and laterally variable), using a specific data transform. Starting from these models, we carry out 3D FWI tests on synthetic and field data, using a relatively straightforward inversion scheme. The field data processing before FWI consists of band-pass filtering and muting of noisy traces. During FWI, a weighting function is applied to the far-offset traces. We test 2D and 3D acquisition layouts, with different positions of the sources and variable offsets. The 3D FWI workflow enriches the overall content of the initial models, allowing a reliable reconstruction of the shallow target, especially when using laterally variable initial models. Moreover, a 3D acquisition layout guarantees a better reconstruction of the target’s shape and lateral extension. In addition, the integration of model-oriented (preliminary monoparametric FWI) and data-oriented (time windowing) strategies into the main optimization scheme has produced further improvement of the FWI results.