bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs
Authors: Giugliano Dario , Longo Miriam , Signoriello Simona , Maiorino Maria Ida , Solerte Bruno , Chiodini Paolo , Esposito Katherine 
Published: March 2022

Abstract
Background
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors reduce cardiorenal outcomes. We performed a network meta-analysis to compare the effect on cardiorenal outcomes among GLP-1 RAs, SGLT-2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors.

Methods
We searched the PUBMED, Embase and Cochrane databases for relevant studies published up until 10 December 2021. Cardiovascular and renal outcome trials reporting outcomes on GLP-1RA, SGLT-2 inhibitors and DPP-4 inhibitors in patients with or without type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE); other outcomes were cardiovascular and total death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure (HHF), and renal outcome.

Results
Twenty-three trials enrolling a total number of 181,143 participants were included. DPP-4 inhibitors did not lower the risk of any cardiorenal outcome when compared with placebo and were associated with higher risks of MACE, HHF, and renal outcome when compared with the other two drug classes. SGLT-2 inhibitors significantly reduced cardiovascular (RR = 0.88) and total (RR = 0.87) death, as compared with DPP-4 inhibitors, while GLP-1 RA reduced total death only (RR = 0.87). The comparison between GLP-1RA and SGLT-2 inhibitors showed no difference in their risks of MACE, nonfatal MI, nonfatal stroke, CV and total death; SGLT-2 inhibitors were superior to GLP-1RA in reducing the risk of HHF and the renal outcome (24% and 22% lower risk, respectively). Only GLP-1RA reduced the risk of nonfatal stroke (RR = 0.84), as compared with placebo. There was no head-to-head trial directly comparing these antidiabetic drug classes.

Conclusions
SGLT-2 inhibitors and GLP-1RA are superior to DPP-4 inhibitors in reducing the risk of most cardiorenal outcomes; SGLT-2 inhibitors are superior to GLP-1RA in reducing the risk of HHF and renal events; GLP-1RA only reduced the risk of nonfatal stroke. Both SGLT-2 inhibitors and GLP-1RA should be the preferred treatment for type 2 diabetes and cardiorenal diseases.
LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in gastric cancer
Authors: Shen Dan-Dan , Pang Jing-Ru , Bi Ya-Ping , Zhao Long-Fei , Li Yin-Rui , Zhao Li-Juan , Gao Ya , Wang Bo , Wang Ning , Wei Liuya , Guo Huiqin , Liu Hong-Min , Zheng Yi-Chao 
Published: March 2022

Abstract
Background
Histone lysine-specific demethylase 1 (LSD1) expression has been shown to be significantly elevated in gastric cancer (GC) and may be associated with the proliferation and metastasis of GC. It has been reported that LSD1 repressed tumor immunity through programmed cell death 1 ligand 1 (PD-L1) in melanoma and breast cancer. The role of LSD1 in the immune microenvironment of GC is unknown.

Methods
Expression LSD1 and PD-L1 in GC patients was analyzed by immunohistochemical (IHC) and Western blotting. Exosomes were isolated from the culture medium of GC cells using an ultracentrifugation method and characterized by transmission electronic microscopy (TEM), nanoparticle tracking analysis (NTA), sucrose gradient centrifugation, and Western blotting. The role of exosomal PD-L1 in T-cell dysfunction was assessed by flow cytometry, T-cell killing and enzyme-linked immunosorbent assay (ELISA).

Results
Through in vivo exploration, mouse forestomach carcinoma (MFC) cells with LSD1 knockout (KO) showed significantly slow growth in 615 mice than T-cell-deficient BALB/c nude mice. Meanwhile, in GC specimens, expression of LSD1 was negatively correlated with that of CD8 and positively correlated with that of PD-L1. Further study showed that LSD1 inhibited the response of T cells in the microenvironment of GC by inducing the accumulation of PD-L1 in exosomes, while the membrane PD-L1 stayed constant in GC cells. Using exosomes as vehicles, LSD1 also obstructed T-cell response of other cancer cells while LSD1 deletion rescued T-cell function. It was found that while relying on the existence of LSD1 in donor cells, exosomes can regulate MFC cells proliferation with distinct roles depending on exosomal PD-L1-mediated T-cell immunity in vivo.

Conclusion
LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in GC; this finding indicates a new mechanism with which LSD1 may regulate cancer immunity in GC and provides a new target for immunotherapy against GC.
Analysing 3429 digital supervisory interactions between Community Health Workers in Uganda and Kenya: the development, testing and validation of an open access predictive machine learning web app
Authors: O’Donovan James , Kahn Ken , MacRae MacKenzie , Namanda Allan Saul , Hamala Rebecca , Kabali Ken , Geniets Anne , Lakati Alice , Mbae Simon M. , Winters Niall 
Published: March 2022

Abstract
Background
Despite the growth in mobile technologies (mHealth) to support Community Health Worker (CHW) supervision, the nature of mHealth-facilitated supervision remains underexplored. One strategy to support supervision at scale could be artificial intelligence (AI) modalities, including machine learning. We developed an open access, machine learning web application (CHWsupervisor) to predictively code instant messages exchanged between CHWs based on supervisory interaction codes. We document the development and validation of the web app and report its predictive accuracy.

Methods
CHWsupervisor was developed using 2187 instant messages exchanged between CHWs and their supervisors in Uganda. The app was then validated on 1242 instant messages from a separate digital CHW supervisory network in Kenya. All messages from the training and validation data sets were manually coded by two independent human coders. The predictive performance of CHWsupervisor was determined by comparing the primary supervisory codes assigned by the web app, against those assigned by the human coders and calculating observed percentage agreement and Cohen’s kappa coefficients.

Results
Human inter-coder reliability for the primary supervisory category of messages across the training and validation datasets was ‘substantial’ to ‘almost perfect’, as suggested by observed percentage agreements of 88–95% and Cohen’s kappa values of 0.7–0.91. In comparison to the human coders, the predictive accuracy of the CHWsupervisor web app was ‘moderate’, suggested by observed percentage agreements of 73–78% and Cohen’s kappa values of 0.51–0.56.

Conclusions
Augmenting human coding is challenging because of the complexity of supervisory exchanges, which often require nuanced interpretation. A realistic understanding of the potential of machine learning approaches should be kept in mind by practitioners, as although they hold promise, supportive supervision still requires a level of human expertise. Scaling-up digital CHW supervision may therefore prove challenging.
Trial registration: This was not a clinical trial and was therefore not registered as such.
Autoimmunity is a hallmark of post-COVID syndrome
Authors: Rojas Manuel , Rodríguez Yhojan , Acosta-Ampudia Yeny , Monsalve Diana M. , Zhu Chengsong , Li Quan-Zhen , Ramírez-Santana Carolina , Anaya Juan-Manuel 
Published: March 2022

AbstractAutoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5–10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.
Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis
Authors: Guan Huanshuai , Kong Ning , Tian Run , Cao Ruomu , Liu Guanzhi , Li Yiyang , Wei Qilu , Jiao Ming , Lei Yutian , Xing Fangze , Tian Peng , Wang Kunzheng , Yang Pei 
Published: March 2022

Abstract
Background
Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown.

Methods
Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis.

Results
Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis.

Conclusions
Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.
3D target location based on RFID polarization phase model
Authors: Shi Wei , Chen Zuhao , Zhao Kun , Xi Wei , Qu Yuhang , He Hui , Guo Zhenge , Ma Zhe , Huang Xuhui , Wang Peng , Dong Bo , Zhao Jizhong 
Published: March 2022

AbstractThe three-dimensional target position is vital to automatic driving, which can efficiently detect the geometrical shape of obstacles and achieve automatic environment recognition for both indoor and outdoor scenarios. In this paper, we propose an RFID 3D localization prototype based on the polarization phase model. To eliminate the impacts of tag angle, we leverage the polarization effect to obtain polarized phases. After that, we use polarized phase decomposition to get pure phases, i.e., the phase corresponding to the line of sight path. Hence, we can calculate the raw phases using the HMFCW algorithm. Finally, we can estimate the target’s 3D position according to unwrapped phase information. In this way, we implement a low-cost, high-precision, easy-for-deployment 3D position solution using commercial UHF RFID hardware. The experiments show that the method can obtain effective positioning results in various environments and achieve positioning accuracy with an average error of about 9 cm.
Structural change in the dairy sector: exit from farming and farm type change
Authors: Zorn Alexander , Zimmert Franziska 
Published: March 2022

AbstractThis paper analyses the factors driving structural change in Swiss dairy farming. We focus on the most important farm type in Switzerland, dairy farms, to examine which factors contribute to a farmer’s decision to abandon farming or change to suckler cow farm type. Swiss dairy farming is characterised by a high proportion of farms with animal welfare programmes and extensive use of grassland. This farm sector can therefore provide a blueprint for sustainable dairy farming, especially in mountain regions. Using administrative data from the agricultural policy information system, the results from logistic regression show that age is a major reason for farm exit. Interestingly, dairy farms that are more specialised reveal higher exit probabilities, whereas farm size in terms of employees and the number of dairy cows as well as the adherence to organic or animal welfare standards reduce the exit probabilities. Changes to the farm type suckler cow occur rather at younger age and by farms that are acquainted with organic and free-range animal husbandry. Finally, there are factors that differently influence farm exit and farm type change. These findings allow for the adjustment of policy instruments to better control structural change of the Swiss dairy farm sector. Given the partly conflicting economic and environmental objectives in agricultural policy, a profound understanding and control of structural development in the agricultural sector is pivotal.
Patient perspectives on premature termination of eating disorder treatment: a systematic review and qualitative synthesis
Authors: Vinchenzo Cecilia , Lawrence Vanessa , McCombie Catherine 
Published: March 2022

Abstract
Background
High rates of premature treatment termination are a well-reported issue in eating disorder treatment, and present a significant barrier for treatment effectiveness and longer term health outcomes of patients with eating disorders. Understanding patient perspectives on this phenomenon is essential in improving treatment completion rates and informing research and intervention development. The aim of this review is to synthesise qualitative literature on patient perspectives of premature termination of eating disorder treatment and to summarise the key issues leading to discontinuation of treatment.

Methods
A systematic review of 1222 articles was conducted to identify studies using qualitative methods to investigate patient experiences of prematurely terminating eating disorder treatment. Ten articles were included in the review, with thematic synthesis used to analyse the primary research and develop overarching analytical themes.

Results
Conflict around enmeshment of eating disorder with identity, and lack of support with reconstructing a sense of self without the eating disorder; challenges of managing pressures of social and clinical relationships while feeling unheard and misunderstood by both; expectations and disappointments around treatment; and dissatisfaction with progress were key themes behind premature termination of treatment.

Conclusions
The findings of this review demonstrate the key issues influencing the decision to end treatment early, highlighting the contribution of individual, environmental, and service-level factors. Implications of these factors are discussed and suggestions raised for future research and service development.
Implementing a peer-to-peer, self-management intervention for young people with depression and anxiety in Denmark
Authors: Lauridsen Sigurd , Nielsen Maj Britt Dahl , Kusier Amalie Oxholm , Cloos Camilla Øst , Jensen Marie Pil , Andersen Susan , Thygesen Lau Casper , Folker Anna Paldam 
Published: March 2022

Abstract
Background
Depressive and anxiety disorders share major risk factors and can often be effectively prevented or treated with similar interventions. However, less than half of young people with mental health problems seek professional help and hence innovative approaches to support this group are needed. To this end Coping with Anxiety and Depression shows promise. The aim of this paper was to evaluate the implementation of Coping with Anxiety and Depression for young people aged 15–25 years showing symptoms of anxiety and/or depression in a Danish community setting.

Methods
The programme was implemented in 39 Danish municipalities. To evaluate the implementation of the programme, we collected quantitative and qualitative data simultaneously and subsequently we triangulated it in the data analysis. The qualitative data collection comprised semi-structured interviews in seven case municipalities. In each municipality we conducted interviews with a local municipality coordinator of the program, a group interview with two voluntary instructors facilitating the program and a group interview with two to seven participants in the programme. In total, seven local coordinators, 14 voluntary instructors and 23 participants (8 men and 15 women) were interviewed. We also carried out a baseline and post-intervention survey. Interview data was coded via an inductive and deductive analysis approach. Survey data was analysed via descriptive statistics in the statistical software programme STATA 16.

Results
The evaluation showed that the implementation of the programme is feasible, and that most participants (83%) were satisfied with the programme to a high/very high extent. In total, 84% of the participants strongly agreed/agreed that it was advantageous that instructors themselves had experience with anxiety and depression. Qualitative data showed that the participants were very positive about the group format. It also showed that recruitment and retention of participants and especially young instructors were challenging but doable. Thus our findings suggest that the programme can be implemented in a way that is perceived as useful and satisfying to young people.

Conclusions
Coping with Anxiety and Depression constitutes a feasible peer-to-peer, group-based community programme that is well-received by its target group. Recruitment and retention of participants and instructors is challenging but doable.
Effect of OSLM features and gamification motivators on motivation in DGBL: pupils' viewpoint
Authors: Leonardou Angeliki , Rigou Maria , Panagiotarou Aliki , Garofalakis John 
Published: March 2022

AbstractThe primary question of this study is whether OLM and OSLM mechanisms, when used in a digital game, offer higher motivation. Furthermore, the study investigates whether a game’s aesthetics and mechanics support players’ intrinsic motivation. Both claims are tested through the design, implementation and pilot use of the Multiplication Game (MG). MG is a digital learning activity that supports pupils in achieving multiplication competence and provides teacher a dashboard to assess and watch own pupils’ performance. The game enriched with gamification elements to engage and motivate participants. Three versions of the game were used by pupils: without any Open Learner Modeling (OLM) support (i.e. without providing access to own progress data), with OLM support and with Open Social Learner Modeling (OSLM) support, to investigate the difference in motivation among these characteristics. After using the MG for a 2-month period, pupils answered a questionnaire anonymously to express their opinion about MG mechanics, MG aesthetics and intrinsic motivation MG can offer. Furthermore, the corresponding teachers were interviewed to provide insights on their attitude towards MG and its functionalities. A statistically significant difference in Intrinsic Motivation (IM) between the three different MG versions was found and a statistically significant difference in MG Aesthetics and Mechanics between the different grades of primary school. Additionally, Intrinsic Motivation was positively correlated with gamification motivators and MG Aesthetics. Participating teachers stated that MG can improve pupils’ multiplication competence and it is worthy of a stable place in the instructional procedure, as it is a means of pupils’ progress tracking and (self-) assessment, as well as a fun way of practicing and developing multiplication skills.
Biomineralization of lithium nanoparticles by Li-resistant Pseudomonas rodhesiae isolated from the Atacama salt flat
Authors: Bruna N. , Galliani E. , Oyarzún P. , Bravo D. , Fuentes F. , Pérez-Donoso J. M. 
Published: March 2022

Abstract
Background
The Atacama salt flat is located in northern Chile, at 2300 m above sea level, and has a high concentration of lithium, being one of the main extraction sites in the world. The effect of lithium on microorganism communities inhabiting environments with high concentrations of this metal has been scarcely studied. A few works have studied the microorganisms present in lithium-rich salt flats (Uyuni and Hombre Muerto in Bolivia and Argentina, respectively). Nanocrystals formation through biological mineralization has been described as an alternative for microorganisms living in metal-rich environments to cope with metal ions. However, bacterial lithium biomineralization of lithium nanostructures has not been published to date. In the present work, we studied lithium-rich soils of the Atacama salt flat and reported for the first time the biological synthesis of Li nanoparticles.

Results
Bacterial communities were evaluated and a high abundance of Cellulomonas, Arcticibacter, Mucilaginibacter, and Pseudomonas were determined. Three lithium resistant strains corresponding to Pseudomonas rodhesiae, Planomicrobium koreense, and Pseudomonas sp. were isolated (MIC > 700 mM). High levels of S2− were detected in the headspace of P. rodhesiae and Pseudomonas sp. cultures exposed to cysteine. Accordingly, biomineralization of lithium sulfide-containing nanomaterials was determined in P. rodhesiae exposed to lithium salts and cysteine. Transmission electron microscopy (TEM) analysis of ultrathin sections of P. rodhesiae cells biomineralizing lithium revealed the presence of nanometric materials. Lithium sulfide-containing nanomaterials were purified, and their size and shape determined by dynamic light scattering and TEM. Spherical nanoparticles with an average size < 40 nm and a hydrodynamic size ~ 44.62 nm were determined.

Conclusions
We characterized the bacterial communities inhabiting Li-rich extreme environments and reported for the first time the biomineralization of Li-containing nanomaterials by Li-resistant bacteria. The biosynthesis method described in this report could be used to recover lithium from waste batteries and thus provide a solution to the accumulation of batteries.