bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study on sports activities in pediatric palliative care: just do it
Authors: Avagnina Irene , Santini Anna , Maghini Irene , Salamon Eleonora , Papa Simonetta , Giacomelli Luca , Perilongo Giorgio , Agosto Caterina , Benini Franca 
Published: April 2023

Abstract
Background
There has been a growing interest in studying the value of physical exercise in children with disabilities or chronic health conditions because of evidence of improvement in quality of life, social acceptance, and physical functioning. However, only scant evidence exists for routine sports activities in children requiring pediatric palliative care (PPC), and in most cases, such evidence has been collected in oncological patients. The Pediatric Hospice of Padua is the referral center for PPC in the Veneto region (northern Italy). Starting from the experience of this PPC center, this pilot study aims to describe the personal experience of children and young people who practice physical activity and their caregivers’ perspectives, focusing particularly on the emotional and social impact of exercise and sports practice.

Methods
Patients involved in at least one regular and structured sports activity were included in the pilot analysis. Two different ICF-CY (International Classification of Functioning, Disability and Health-Children and Youth Version) scales (“Body Function” and “Activity and Participation”) were filled out to assess the children’s global functional competence. Two online ad hoc questionnaires were created and administered to children, when able to respond, and caregivers.

Results
A total of 9% of patients reported being involved in a sports activity. All children who played sports did not have indications of cognitive retardation. The most practiced sport was swimming. The use of standardized methods such as ICF-CY shown that severe motor impairments do not limit sports accessibility. Questionnaires result suggest that sports are a positive experience for both children needing PPC and their parents. Children encourage other children to do sports and can find the positive side even in difficulties.

Conclusion
Since PPC is encouraged as early as the diagnosis of incurable pathologies, the inclusion of sports activities in the context of a PPC plan should be considered from the perspective of improving quality of life.
A mechanically validated open-source silicone model for the training of gastric perforation sewing
Authors: Warnung Lukas , Sattler Stefan , Haiden Elmar , Schober Sophie , Pahr Dieter , Reisinger Andreas 
Published: April 2023

Abstract
Background
Gastrointestinal perforation is commonly seen in emergency departments. The perforation of the stomach is an emergency situation that requires immediate surgical treatment. The necessary surgical skills require regular practical training. Owing to patient`s safety, in vivo training opportunities in medicine are restricted. Animal tissue especially porcine tissue, is commonly used for surgical training. Due to its limiting factors, artificial training models are often to be preferred. Many artificial models are on the market but to our knowledge, none that mimic the haptic- and sewing properties of a stomach wall at the same time. In this study, an open source silicone model of a gastric perforation for training of gastric sewing was developed that attempts to provide realistic haptic- and sewing behaviour.

Methods
To simulate the layered structure of the human stomach, different silicone materials were used to produce three different model layups. The production process was kept as simple as possible to make it easily reproducible. A needle penetration setup as well as a systematic haptic evaluation were developed to compare these silicone models to a real porcine stomach in order to identify the most realistic model.

Results
A silicone model consisting of three layers was identified as being the most promising and was tested by clinical surgeons.

Conclusions
The presented model simulates the sewing characteristics of a human stomach wall, is easily reproducible at low-costs and can be used for practicing gastric suturing techniques.

Trial registrations
Not applicable.
Barriers and facilitators to training delivery and subsequent implementation of a localised child and adolescent mental health initiative: a qualitative content analysis
Authors: Banwell Emily , Qualter Pamela , Humphrey Neil 
Published: April 2023

Abstract
Background
Ensuring that children and young people (CYP) can obtain mental health support from a broad variety of sources is of upmost importance. This is especially true given the increasing prevalence of mental health difficulties in this population, and the associated challenges with receiving support from specialised healthcare services. Equipping professionals, from a wide range of sectors, with the skills needed to provide this support is a vital starting point. This study explored the experiences of professionals who had participated in CYP mental health training modules that related directly to the local implementation of the THRIVE Framework for System Change in Greater Manchester, UK (GM i-THRIVE) to establish the perceived barriers and facilitators behind the implementation of this training programme.

Methods
Directed qualitative content analysis of semi-structured interview data from nine CYP-facing professionals was conducted. Both the interview schedule and initial deductive coding strategy were developed using the findings of a systematic literature review by the authors, that was conducted to explore wider CYP mental health training experiences. This methodology was used to establish the presence or absence of these findings within GM i-THRIVE, before generating tailored recommendations for their training programme.

Results
When the interview data were coded and analysed, a strong level of thematic similarity with the authors’ review was found. However, we deduced that the emergence of additional themes might reflect the contextual uniqueness of GM i-THRIVE, that is likely to be further compounded by the COVID-19 pandemic. Six recommendations were made for further improvement. These included the facilitation of unstructured peer interaction during training, and ensuring that jargon and key words are fully clarified.

Conclusions
Methodological limitations, guidance for usage, and potential applications of the study’s findings are explored. Whilst the findings were largely akin to those of the review, subtle yet important differences were found. These are likely to reflect the nuances of the training programme discussed, however, we tentatively suggest that our findings are transferable to similar training interventions. This study provides a valuable example of how qualitative evidence syntheses can be used to aid study design and analysis: an underused approach.
The impact of metabolic endotoxaemia on the browning process in human adipocytes
Authors: Omran Farah , Murphy Alice M. , Younis Awais Z. , Kyrou Ioannis , Vrbikova Jana , Hainer Vojtech , Sramkova Petra , Fried Martin , Ball Graham , Tripathi Gyanendra , Kumar Sudhesh , McTernan Philip G. , Christian Mark 
Published: April 2023

Abstract
Background
Dysfunctional adipose tissue (AT) is known to contribute to the pathophysiology of metabolic disease, including type 2 diabetes mellitus (T2DM). This dysfunction may occur, in part, as a consequence of gut-derived endotoxaemia inducing changes in adipocyte mitochondrial function and reducing the proportion of BRITE (brown-in-white) adipocytes. Therefore, the present study investigated whether endotoxin (lipopolysaccharide; LPS) directly contributes to impaired human adipocyte mitochondrial function and browning in human adipocytes, and the relevant impact of obesity status pre and post bariatric surgery.

Methods
Human differentiated abdominal subcutaneous (AbdSc) adipocytes from participants with obesity and normal-weight participants were treated with endotoxin to assess in vitro changes in mitochondrial function and BRITE phenotype. Ex vivo human AbdSc AT from different groups of participants (normal-weight, obesity, pre- and 6 months post-bariatric surgery) were assessed for similar analyses including circulating endotoxin levels.

Results
Ex vivo AT analysis (lean & obese, weight loss post-bariatric surgery) identified that systemic endotoxin negatively correlated with BAT gene expression (p < 0.05). In vitro endotoxin treatment of AbdSc adipocytes (lean & obese) reduced mitochondrial dynamics (74.6% reduction; p < 0.0001), biogenesis (81.2% reduction; p < 0.0001) and the BRITE phenotype (93.8% reduction; p < 0.0001). Lean AbdSc adipocytes were more responsive to adrenergic signalling than obese AbdSc adipocytes; although endotoxin mitigated this response (92.6% reduction; p < 0.0001).

Conclusions
Taken together, these data suggest that systemic gut-derived endotoxaemia contributes to both individual adipocyte dysfunction and reduced browning capacity of the adipocyte cell population, exacerbating metabolic consequences. As bariatric surgery reduces endotoxin levels and is associated with improving adipocyte functionality, this may provide further evidence regarding the metabolic benefits of such surgical interventions.
Nutritional and immunological evaluation of Nannochloropsis oculata as a potential Nile tilapia-aquafeed supplement
Authors: Zahran Eman , Elbahnaswy Samia , Ahmed Fatma , Ibrahim Iman , Khaled Asmaa A. , Eldessouki Elsayed A. 
Published: April 2023

AbstractNannochloropsis oculata (N. oculata) is a marine microalga containing bioactive compounds and a high omega-3 polyunsaturated fatty acid (ω-3 PUFAs). Therefore, it is very promising for nutraceutical and the functional food industry applications. Three groups of Nile tilapia (forty-five fish/group) were fed on basal diets or diets containing 5% (N5) or 10% (N10) of the microalga N. oculata for seven weeks. Fish growth performance, proximate composition, and lipid (fatty acids/ FAs and lipoproteins) profile were estimated. In addition, the expression pattern of some lipid metabolism and immune-relevant genes were assessed. An enhancement in whole body crude protein and growth indices of Nile tilapia was observed on both the supplemented groups N5 and N10. Higher levels of high-density lipoproteins (HDL); and lower levels of the low-density lipoproteins (LDL) were evident in both supplemented groups, while the cholesterol and triglycerides (TG) levels were similar among groups. Ω-3 PUFAs were the significant FAs profile of tilapia fed on N. oculata-supplemented diets in terms of eicosapentaenoic acid, docosahexaenoic acid, and n3/n6 ratio. Concerning the gene expression pattern, heat-shock protein70, glutathione-S-transferase, glutathione peroxidase, and interleukin-1β (IL-1β) were elevated significantly in both supplemented groups. IL-10 is only upregulated in the N10 group. The lipid metabolism-related gene expression showed downregulation of only fatty acid synthase (FAS) in both supplemented groups, with no statistical changes in Peroxisome proliferator-activated receptor alpha (PPARα). Tumor necrosis factor-α (TNF-α), Transforming growth factor-β1 (TGF-β1), and the apoptotic related genes [caspase3 and Proliferating cell nuclear antigen (PCNA)] showed insignificant changes among groups. The histopathological examination of the intestine, liver, and spleen supports our findings and confirms the benefits and safeness of N. oculata dietary inclusion. Collectively, N. oculata is a very promising nutraceutical for improving fish health and sustainability of aquaculture production.
Graphical Abstract
Integrated microbiome and metabolome analysis reveals novel urinary microenvironmental signatures in interstitial cystitis/bladder pain syndrome patients
Authors: Zheng Zhenming , Hu Jintao , Li Wenshuang , Ma Kaiqun , Zhang Caixia , Li Kuiqing , Yao Yousheng 
Published: April 2023

Abstract
Background
The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) has not been elucidated, but urinary microorganisms and metabolites have been shown to be closely associated with the inflammatory response of IC/BPS. Nevertheless, the exact mechanisms related to this response have not been clarified.

Methods
16S rRNA sequencing and untargeted metabolomics techniques were used to analyse the urinary microbial and metabolite profiles of 30 IC/BPS patients and 30 healthy controls, and correlation analyses were performed to explore the mechanisms by which they might be involved in the inflammatory response of IC/BPS.

Results
Twenty-eight differential genera, such as Lactobacillus and Sphingomonas, were identified. A total of 44 differential metabolites such as 1,3,7-trimethyluric acid and theophylline were screened. The abundance of Lactobacillus and Escherichia-Shigella was significantly higher in the urine of female IC/BPS patients and healthy controls compared to males, while Bacteroides and Acinetobacter were lower than in males. The results of the Pearson correlation analysis suggested that differential microorganisms may influence the composition of metabolites. The Lactobacillus genus may be a protective bacterium against IC/BPS, whereas Sphingomonas may be a pathogenic factor. The differential metabolite theophylline, as an anti-inflammatory substance, may downregulate the inflammatory response of IC/BPS.

Conclusions
This study revealed microbial and metabolite profiles in the urine of IC/BPS patients versus healthy controls in both males and females. We also found some microorganisms and metabolites closely related to the inflammatory response of IC/BPS, which provided directions for future aetiological and therapeutic research.
The interplay between human papillomavirus and vaginal microbiota in cervical cancer development
Authors: Sharifian Kimia , Shoja Zabihollah , Jalilvand Somayeh 
Published: April 2023

AbstractOver the past few decades, we have grown accustomed to the idea that human papillomavirus can cause tumors. The genetic and environmental factors that make the difference between elimination of viral infection and the development of cancer are therefore an area of active investigation at present. Microbiota has emerged as an important factor that may affect this balance by increasing or decreasing the ability of viral infection to promote. The female reproductive system has its specific microbiota that helps to maintain health and prevent infection with pathogens. In contrast to other mucosal sites, the vaginal microbiota typically has low diversity and contains few Lactobacillus spp. which by using high-throughput 16s rRNA gene sequencing, classified into five different community state types. According to emerging information, increased diversity of vaginal microbiota and reduced abundance of Lactobacillus spp. contribute to HPV acquisition, persistence, and development of cervical cancer. In this review, the role of normal female reproductive tract microbiota in health, mechanisms which dysbiosis can cause diseases through interaction with microbes and several therapeutic approaches were addressed.
Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice
Authors: Li Zhen , Chen Zhenyue , Chen Jiayi , Liu Zhutong , Li Zehui , Sun He , Wang Xiaochao , Wei Jinqiang , Cao Xuewei , Zheng Decai 
Published: April 2023

AbstractBackgroundOsteoarthritis (OA) is a chronic degenerative joint disease characterized by loss of joint function, which seriously reduces the quality of life of the elderly and imposes a heavy socioeconomic burden worldwide. Monotropein (MON), the main active ingredient ofMorinda officinalisF.C. How, has exhibited therapeutic effects in different disease models. However, its potential effects on chondrocytes in an arthritic model remain unclear. This study aimed to evaluate the effects of MON in chondrocytes and a mouse model of OA, and explore the potential mechanisms.Materials and methodsMurine primary chondrocytes were pretreated with 10 ng/ml interleukin (IL)-1β for 24 h to establish an in vitro model of OA, and then treated with different concentrations of MON (0, 25, 50 and 100 μM) for 24 h. The proliferation of the chondrocytes was assayed using ethynyl-deoxyuridine (EdU) staining. Immunofluorescence staining, western blotting and TUNEL staining were performed to assess the effects of MON on cartilage matrix degradation, apoptosis and pyroptosis. The mouse model of OA was constructed by surgical destabilization of the medial meniscus (DMM), and the animals were randomly divided into the sham-operated, OA and OA + MON groups. Following OA induction, the mice were given intraarticular injection of 100 μM MON or equal volume of normal saline twice a week for 8 weeks. The effects of MON on cartilage matrix degradation, apoptosis and pyroptosis were assessed as indicated.ResultsMON significantly accelerated the proliferation of chondrocytes, and inhibited cartilage matrix degradation, apoptosis and pyroptosis in the IL-1β-stimulated cells by blocking the nuclear factor-kappa B (NF-κB) signaling pathway. In the mouse model as well, MON treatment alleviated OA progression and promoted cartilage repair by inhibiting cartilage matrix degradation, and chondrocyte apoptosis and pyroptosis through the inactivation of the NF-κB signaling pathway. Furthermore, the MON-treated arthritic mice exhibited better articular tissue morphology and lower OARSI scores.ConclusionsMON alleviated OA progression by inhibiting cartilage matrix degradation, and the apoptosis and pyroptosis of chondrocytes via NF-κB pathway inactivation, and is a promising alternative for the treatment of OA.
Subjective and objective survival prediction in mechanically ventilated critically ill patients: a prospective cohort study
Authors: Boeck Lucas , Pargger Hans , Schellongowski Peter , Luyt Charles-Edouard , Maggiorini Marco , Jahn Kathleen , Muller Grégoire , Lötscher Rene , Bucher Evelyne , Cueni Nadine , Staudinger Thomas , Chastre Jean , Siegemund Martin , Tamm Michael , Stolz Daiana 
Published: April 2023

Abstract
Background
ICU risk assessment tools, routinely used for predicting population outcomes, are not recommended for evaluating individual risk. The state of health of single patients is mostly subjectively assessed to inform relatives and presumably to decide on treatment decisions. However, little is known how subjective and objective survival estimates compare.

Methods
We performed a prospective cohort study in mechanically ventilated critically ill patients across five European centres, assessed 62 objective markers and asked the clinical staff to subjectively estimate the probability of surviving 28 days.

Results
Within the 961 included patients, we identified 27 single objective predictors for 28-day survival (73.8%) and pooled them into predictive groups. While patient characteristics and treatment models performed poorly, the disease and biomarker models had a moderate discriminative performance for predicting 28-day survival, which improved for predicting 1-year survival. Subjective estimates of nurses (c-statistic [95% CI] 0.74 [0.70–0.78]), junior physicians (0.78 [0.74–0.81]) and attending physicians (0.75 [0.72–0.79]) discriminated survivors from non-survivors at least as good as the combination of all objective predictors (c-statistic: 0.67–0.72). Unexpectedly, subjective estimates were insufficiently calibrated, overestimating death in high-risk patients by about 20% in absolute terms. Combining subjective and objective measures refined discrimination and reduced the overestimation of death.

Conclusions
Subjective survival estimates are simple, cheap and similarly discriminative as objective models; however, they overestimate death risking that live-saving therapies are withheld. Therefore, subjective survival estimates of individual patients should be compared with objective tools and interpreted with caution if not agreeing.
Trial registration ISRCTN ISRCTN59376582, retrospectively registered October 31st 2013.
PAUSE: principled feature attribution for unsupervised gene expression analysis
Authors: Janizek Joseph D. , Spiro Anna , Celik Safiye , Blue Ben W. , Russell John C. , Lee Ting-I , Kaeberlin Matt , Lee Su-In 
Published: April 2023

AbstractAs interest in using unsupervised deep learning models to analyze gene expression data has grown, an increasing number of methods have been developed to make these models more interpretable. These methods can be separated into two groups: post hoc analyses of black box models through feature attribution methods and approaches to build inherently interpretable models through biologically-constrained architectures. We argue that these approaches are not mutually exclusive, but can in fact be usefully combined. We propose PAUSE (https://github.com/suinleelab/PAUSE), an unsupervised pathway attribution method that identifies major sources of transcriptomic variation when combined with biologically-constrained neural network models.
Optimal statin use for prevention of sepsis in type 2 diabetes mellitus
Authors: Sun Mingyang , Tao Yuan , Chen Wan-Ming , Wu Szu-Yuan , Zhang Jiaqiang 
Published: April 2023

Abstract
Purpose
To investigate the dose-dependent protective effects of statins, specific classes of statins, and different intensities of statin use on sepsis risk in patients with type 2 diabetes mellitus (T2DM).

Methods
We included patients with T2DM aged  ≥ 40 years. Statin use was defined as the use of statin on most days for  > 1 months with a mean statin dose of  ≥ 28 cumulative defined daily doses (cDDDs) per year (cDDD-year). An inverse probability of treatment-weighted Cox hazard model was used to investigate the effects of statin use on sepsis and septic shock while considering statin use status as a time-dependent variable.

Results
From 2008 to 2020, a total of 812 420 patients were diagnosed as having T2DM. Among these patients, 118,765 (27.79%) statin nonusers and 50 804 (12.03%) statin users developed sepsis. Septic shock occurred in 42,755 (10.39%) individuals who did not use statins and 16,765 (4.18%) individuals who used statins. Overall, statin users had a lower prevalence of sepsis than did nonusers. The adjusted hazard ratio (aHR) of statin use was 0.37 (95% CI 0.35, 0.38) for sepsis compared with no statin use. Compared with the patients not using statins, those using different classes of statins exhibited a more significant reduction in sepsis, with aHRs (95% CIs) of sepsis being 0.09 (0.05, 0.14), 0.32 (0.31, 0.34), 0.34 (0.32, 0.36), 0.35 (0.32, 0.37), 0.37 (0.34, 0.39), 0.42 (0.38, 0.44), and 0.54 (0.51, 0.56) for pitavastatin, pravastatin, rosuvastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin use, respectively. In the patients with different cDDD-years of statins, multivariate analysis indicated a significant reduction in sepsis, with aHRs of 0.53 (0.52, 0.57), 0.40 (0.39, 0.43), 0.29 (0.27, 0.30), and 0.17 (0.15, 0.19) for Q1, Q2, Q3, and Q4 cDDD-years (P for trend < 0.0001). The optimal daily statin dose of 0.84 DDD was associated with the lowest aHR. Similar trends of higher cDDD-year and specific statin types use were associated with a decrease in septic shock when compared to statin non-users.

Conclusion
Our real-world evidence demonstrated that the persistent use of statins reduced sepsis and septic shock risk in patients with T2DM and a higher cDDD-year of statin use was associated with an increased reduction of sepsis and septic shock risk in these patients.