bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)
Authors: O’Hearn Katie , Menon Kusum , Weiler Hope A. , Amrein Karin , Fergusson Dean , Gunz Anna , Bustos Raul , Campos Roberto , Catalan Valentina , Roedl Siegfried , Tsampalieros Anne , Barrowman Nick , Geier Pavel , Henderson Matthew , Khamessan Ali , Lawson Margaret L. , McIntyre Lauralyn , Redpath Stephanie , Jones Glenville , Kaufmann Martin , McNally Dayre ,   the Canadian Critical Care Trials Group
Published: August 2023

Abstract
Background
Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU.

Methods
We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial.

Results
Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%).

Conclusions
A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up.
Trial Registration.
Clinicaltrials.gov NCT02452762 Registered 25/05/2015.
Trusted residents and housing assistance to decrease violence exposure in New Haven (TRUE HAVEN): a strengths-based and community-driven stepped-wedge intervention to reduce gun violence
Authors: Tong Guangyu , Spell Virginia T. , Horton Nadine , Thornhill Thomas , Keene Danya , Montgomery Christine , Spiegelman Donna , Wang Emily A. , Roy Brita 
Published: August 2023

Abstract
Background
We describe the rationale and study design for “TRUsted rEsidents and Housing Assistance to decrease Violence Exposure in New Haven (TRUE HAVEN),” a prospective type 1 hybrid effectiveness/implementation study of a multi-level intervention using a stepped wedge design. TRUE HAVEN aims to lower rates of community gun violence by fostering the stability, wealth, and well-being of individuals and families directly impacted by incarceration through the provision of stable housing and by breaking the cycle of trauma.

Design
TRUE HAVEN is an ongoing, multi-level intervention with three primary components: financial education paired with housing support (individual level), trauma-informed counseling (neighborhood level), and policy changes to address structural racism (city/state level). Six neighborhoods with among the highest rates of gun violence in New Haven, Connecticut, will receive the individual and neighborhood level intervention components sequentially beginning at staggered 6-month steps. Residents of these neighborhoods will be eligible to participate in the housing stability and financial education component if they were recently incarcerated or are family members of currently incarcerated people; participants will receive intense financial education and follow-up for six months and be eligible for special down payment and rental assistance programs. In addition, trusted community members and organization leaders within each target neighborhood will participate in trauma-informed care training sessions to then be able to recognize when their peers are suffering from trauma symptoms, to support these affected peers, and to destigmatize accessing professional mental health services and connect them to these services when needed. Finally, a multi-stakeholder coalition will be convened to address policies that act as barriers to housing stability or accessing mental healthcare. Interventions will be delivered through existing partnerships with community-based organizations and networks. The primary outcome is neighborhood rate of incident gun violence. To inform future implementation and optimize the intervention package as the study progresses, we will use the Learn As You Go approach to optimize and assess the effectiveness of the intervention package on the primary study outcome.

Discussion
Results from this protocol will yield novel evidence for whether and how addressing structural racism citywide leads to a reduction in gun violence.

Trial registration
ClinicalTrials.gov Identifier: NCT05723614. Registration date: February 01, 2023. Please refer to https://clinicaltrials.gov/ct2/show/NCT05723614 for public and scientific inquiries.
Characterization of tea (Camellia sinensis L.) flower extract and insights into its antifungal susceptibilities of Aspergillus flavus
Authors: Chen Fangfang , Chen Yu-Pei , Wu Hongtan , Li Ya , Zhang Shudi , Ke Jincheng , Yao Jeng-Yuan 
Published: August 2023

Abstract
Background
Tea (Camellia sinensis L.) flowers will compete with tea leaves in nutrition and are abandoned as an undesirable by-product. In this study, the biological efficacy of tea flowers was investigated. Further exploration of its antifungal activity was explained.

Methods
Tea flowers harvested from China were characterized in term of component, antioxidant ability, tyrosinase inhibition, and antifungal ability. Chemical compounds of tea flowers were analyzed by LC-MS. Disinfectant compounds were identified in tea flowers, and 2-ketobutyric acid exhibited antifungal activity against Aspergillus flavusCCTCC AF 2023038. The antifungal mechanism of 2-ketobutyric acid was further investigated by RNA-seq.

Results
Water-soluble tea flower extracts (TFEs) exhibited free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) as well as a high ferric-reducing ability. However, no inhibition of tyrosinase activity was observed. In the antifungal test, 6.4 mg/mL TFE reached 71.5% antifungal rate and the electrical conductivity of the culture broth increased with increasing concentration of TFE, implying that it damaged the fungal cell membrane by the TFE. Several disinfectants were identified in TFE by LC-MS, and 2-ketobutyric acid was also confirmed to be capable of fungal inhibition. Propidium iodide (PI) staining indicated that 2-ketobutyric acid caused damage to the cell membrane. RNA-seq analysis revealed that 3,808 differentially expressed genes (DEGs) were found in A. flavus CCTCC AF 2023038 treated by 2-ketobutyric acid, and more than 1,000 DEGs involved in the integral and intrinsic component of membrane were affected. Moreover, 2-ketobutyric acid downregulated aflatoxin biosynthesis genes and decreased the aflatoxin production.

Conclusions
Overall, TFE exhibited excellent antioxidant ability and fungal inhibition against A. flavus CCTCC AF 2023038 due to its abundant disinfectant compounds. As a recognized food additive, 2-ketobutyric acid is safe to use in the food industry and can be utilized as the basis for the research and development of strong fungicides.
Shared decision making and advance care planning: a systematic literature review and novel decision-making model
Authors: Rosca Ana , Karzig-Roduner Isabelle , Kasper Jürgen , Rogger Niek , Drewniak Daniel , Krones Tanja 
Published: August 2023

AbstractBackground and AimsShared decision making (SDM) and advance care planning (ACP) are important evidence and ethics based concepts that can be translated in communication tools to aid the treatment decision-making process. Although both have been recommended in the care of patients with risks of complications, they have not yet been described as two components of one single process. In this paper we aim to (1) assess how SDM and ACP is being applied, choosing patients with aortic stenosis with high and moderate treatment complication risks such as bleeding or stroke as an example, and (2) propose a model to best combine the two concepts and integrate them in the care process.MethodsIn order to assess how SDM and ACP is applied in usual care, we have performed a systematic literature review. The included studies have been analysed by means of thematic analysis as well as abductive reasoning to determine which SDM and ACP steps are applied as well as to propose a model of combining the two concepts into one process.ResultsThe search in Medline, Cinahl, Embase, Scopus, Web of science, Psychinfo and Cochrane revealed 15 studies. Eleven describe various steps of SDM while four studies discuss the documentation of goals of care. Based on the review results and existing evidence we propose a model that combines SDM and ACP in one process for a complete patient informed choice.ConclusionTo be able to make informed choices about immediate and future care, patients should be engaged in both SDM and ACP decision-making processes. This allows for an iterative process in which each important decision-maker can share their expertise and concerns regarding the care planning and advance care planning. This would help to better structure and prioritize information while creating a trustful and respectful relationship between the participants.PROSPERO 2019.CRD42019124575
The impact of the three-level collaboration exercise on collaboration and leadership during scenario-based hospital evacuation exercises using flexible surge capacity concept: a mixed method cross-sectional study
Authors: Phattharapornjaroen Phatthranit , Carlström Eric , Atiksawedparit Pongsakorn , Holmqvist Lina Dahlén , Pitidhammabhorn Dhanesh , Sittichanbuncha Yuwares , Khorram-Manesh Amir 
Published: August 2023

Abstract
Background
Hospitals play a crucial role in responding to disasters and public health emergencies. However, they are also vulnerable to threats such as fire or flooding and can fail to respond or evacuate adequately due to unpreparedness and lack of evacuation measures. The United Nations Office for Disaster Risk Reduction has emphasised the importance of partnerships and capacity building in disaster response. One effective way to improve and develop disaster response is through exercises that focus on collaboration and leadership. This study aimed to examine the effectiveness of using the 3-level collaboration (3LC) exercise in developing collaboration and leadership in districts in Thailand, using the concept of flexible surge capacity (FSC) and its collaborative tool during a hospital evacuation simulation.

Methods
A mixed-method cross-sectional study was conducted with 40 participants recruited from disaster-response organisations and communities. The data from several scenario-based simulations were collected according to the collaborative elements (Command and control, Safety, Communication, Assessment, Triage, Treatment, Transport), in the disaster response education, “Major Incident Medical Management and Support” using self-evaluation survey pre- and post-exercises, and direct observation.

Results
The 3LC exercise effectively facilitated participants to gain a mutual understanding of collaboration, leadership, and individual and organisational flexibility. The exercise also identified gaps in communication and the utilisation of available resources. Additionally, the importance of early community engagement was highlighted to build up a flexible surge capacity during hospital evacuation preparedness.

Conclusions
the 3LC exercise is valuable for improving leadership skills and multiagency collaboration by incorporating the collaborative factors of Flexible Surge Capacity concept in hospital evacuation preparedness.
Effect of two insect meals on the gut commensal microbiome of healthy sea trout (Salmo trutta vr. trutta)
Authors: Józefiak Agata , Rawski Mateusz , Kierończyk Bartosz , Józefiak Damian , Mazurkiewicz Jan 
Published: August 2023

Abstract
Background
The balance of the intestinal commensal microbiome of fish and other animals plays an important role in the physiological processes of healthy animals, contributes to the defense against pathogens, stimulates the immune system and facilitates nutrient metabolism. In the last decade, the interest in the application of the insects in fish nutrition increased, although little is known regarding the effects of insect meals on the gastrointenstinal tract microbiome of the sea trout fingerlings. The aim of this study was to evaluate the effect of two diets containing mealworm (MW) and superworm (SW) on the microbiome of the digesta of sea trout fingerlings and the relative abundances of different taxa among communities under controlled conditions.

Results
The insect meals produced a similar weight gain and survival rate to sea trout fed fishmeal. The most abundant bacterial phylum in all the treatment groups was Firmicutes followed by Proteobacteria and Actinobacteria, and significant differences in the amount of Cyanobacteria were observed in the SW group.

Conclusions
The insect meals did not produce differences in the three most abundant phyla in the sea trout digesta. However, the effect of each type of meal on the lower taxonomic levels was evident, particularly in the case of the superworm meal. These microbiome differences indicated that mealworm meal was more related to fishmeal than superworm meal. Our results highlight the potential effects of insect meals, such as mealworm and superworm meals, on the microbiota of sea trout.
The RNA-binding protein KSRP aggravates malignant progression of clear cell renal cell carcinoma through transcriptional inhibition and post-transcriptional destabilization of the NEDD4L ubiquitin ligase
Authors: Yang Yi-Chieh , Lin Yung-Wei , Lee Wei-Jiunn , Lai Feng-Ru , Ho Kuo-Hao , Chu Chih-Ying , Hua Kuo-Tai , Chen Ji-Qing , Tung Min-Che , Hsiao Michael , Wen Yu-Ching , Chien Ming-Hsien 
Published: August 2023

Abstract
Background
KH-type splicing regulatory protein (KHSRP, also called KSRP), a versatile RNA-binding protein, plays a critical role in various physiological and pathological conditions through modulating gene expressions at multiple levels. However, the role of KSRP in clear cell renal cell carcinoma (ccRCC) remains poorly understood.

Methods
KSRP expression was detected by a ccRCC tissue microarray and evaluated by an in silico analysis. Cell loss-of-function and gain-of-function, colony-formation, anoikis, and transwell assays, and an orthotopic bioluminescent xenograft model were conducted to determine the functional role of KRSP in ccRCC progression. Micro (mi)RNA and complementary (c)DNA microarrays were used to identify downstream targets of KSRP. Western blotting, quantitative real-time polymerase chain reaction, and promoter- and 3-untranslated region (3'UTR)-luciferase reporter assays were employed to validate the underlying mechanisms of KSRP which aggravate progression of ccRCC.

Results
Our results showed that dysregulated high levels of KSRP were correlated with advanced clinical stages, larger tumor sizes, recurrence, and poor prognoses of ccRCC. Neural precursor cell-expressed developmentally downregulated 4 like (NEDD4L) was identified as a novel target of KSRP, which can reverse the protumorigenic and prometastatic characteristics as well as epithelial-mesenchymal transition (EMT) promotion by KSRP in vitro and in vivo. Molecular studies revealed that KSRP can decrease NEDD4L messenger (m)RNA stability via inducing mir-629-5p upregulation and directly targeting the AU-rich elements (AREs) of the 3’UTR. Moreover, KSRP was shown to transcriptionally suppress NEDD4L via inducing the transcriptional repressor, Wilm's tumor 1 (WT1). In the clinic, ccRCC samples revealed a positive correlation between KSRP and mesenchymal-related genes, and patients expressing high KSRP and low NEDD4L had the worst prognoses.

Conclusion
The current findings unveil novel mechanisms of KSRP which promote malignant progression of ccRCC through transcriptional inhibition and post-transcriptional destabilization of NEDD4L transcripts. Targeting KSRP and its pathways may be a novel pharmaceutical intervention for ccRCC.
Rhizopus stolonifer biomass catalytic transesterification capability: optimization of cultivation conditions
Authors: Elhussieny Nadeem I. , El-Refai Heba A. , Mohamed Sayeda S. , Shetaia Yousseria M. , Amin Hala A. , Klöck Gerd 
Published: August 2023

AbstractBackgroundUsing fungal biomass for biocatalysis is a potential solution for the expensive cost of the use o enzymes. Production of fungal biomass with effective activity requires optimizing the cultivation conditions.ResultsRhizopus stoloniferbiomass was optimized for transesterification and hydrolysis of waste frying oil (WFO). Growth and biomass lipolytic activities ofR. stoloniferimproved under shaking conditions compared to static conditions, and 200 rpm was optimum. As biomass lipase and transesterification activities inducer, olive oil was superior to soybean, rapeseed, and waste frying oils. Biomass produced in culture media containing fishmeal as an N-source feedstock had higher lipolytic capabilities than corn-steep liquor and urea. Plackett Burman screening of 9 factors showed that pH (5–9), fishmeal (0.25–1.7%, w/v), and KH2PO4(0.1–0.9%, w/v) were significant factors with the highest main effect estimates 11.46, 10.42, 14.90, respectively. These factors were selected for response surface methodology (RSM) optimization using central composite design (CCD). CCD models for growth, biomass lipase activity, and transesterification capability were significant. The optimum conditions for growth and lipid modification catalytic activities were pH 7.4, fishmeal (2.62%, w/v), and KH2PO4 (2.99%, w/v).ConclusionOptimized culture conditions improved the whole cell transesterification capability ofRhizopus stoloniferbiomass in terms of fatty acid methyl ester (FAME) concentration by 67.65% to a final FAME concentration of 85.5%, w/w.
Elevated levels of neutrophil related chemokine citrullinated histone H3, interleukin-8 and C-reaction protein in patients with immune checkpoint inhibitor therapy: predictive biomarkers for response to treatment
Authors: Wang Xueping , Huang Hao , Zhang Lin , Wu Yaxian , Wen Yingsheng , Weng Xuezi , Chen Qi , Liu Wanli 
Published: August 2023

Abstract
Background
Immune checkpoint inhibitor (ICI) therapy has been used in various tumors. The biomarkers predictive of a response to ICI treatment remain unclear, and additional and combined biomarkers are urgently needed. Secreted factors related to the tumor microenvironment (TME) have been evaluated to identify novel noninvasive predictive biomarkers.

Methods
We analyzed 85 patients undergoing ICI therapy as the primary cohort. The associations between ICI response and all biomarkers were evaluated. A prediction model and a nomogram were developed and validated based on the above factors.

Results
Seventy-seven patients were enrolled in the validation cohort. In the primary cohort, the baseline serum levels of H3Cit, IL-8 and CRP were significantly higher in nonresponder patients. A model based on these three factors was developed, and the “risk score” of an ICI response was calculated with the formula: “risk score” = 3.4591×H3Cit + 2.5808×IL8 + 2.0045 ×CRP– 11.3844. The cutoff point of the “risk score” was 0.528, and patients with a “risk score” lower than 0.528 were more likely to benefit from ICI treatment (AUC: 0.937, 95% CI: 0.886–0.988, with sensitivity 80.60%, specificity 91.40%). The AUC was 0.719 (95% CI: 0.600-0.837, P = 0.001), with a sensitivity of 70.00% and specificity of 65.20% in the validation cohort.

Conclusions
A model incorporating H3Cit, IL-8 and CRP has an excellent prediction ability for ICI response; thus, patients with a lower “risk score” selectively benefit from ICI treatment, which may have significant clinical implications for the early detection of an ICI response.
Distorted thoughts as a mediator of depressive symptoms in patients with major depressive disorder: a longitudinal study
Authors: Carneiro Adriana Munhoz , Pereira Danilo Assis , Fernandes Fernando , Baptista Makilim Nunes , Brunoni André Russowsky , Moreno Ricardo Alberto 
Published: August 2023

Abstract
Background
Distorted thoughts are common in Major Depressive Disorder (MDD), and can impact patients’ perceptions of depression severity, and predict chronicity and treatment response. This study aimed to investigate whether distorted thoughts mediate depressive symptoms in MDD over a 6-month period.

Method
These are secondary results from a study that followed 119 patients diagnosed with moderate to severe MDD for 6 months. Diagnoses were confirmed by the Structured Interview for DSM-IV (SCID-CV). The analysis was composed of results from the Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS), the second edition of the Beck Depression Inventory (BDI-II), and the Depression Thoughts Scale (DTS) collected at weeks 1, 8, 12 and 24.

Results
Results showed that the DTS mediated the relationship between depressive symptoms experienced approximately 3 months after starting antidepressant treatment.

Conclusion
Cognitive distortions were linked as a mediator to depressive symptoms, highlighting the importance of early psychological interventions in patients with MDD who exhibit these distortions.

Trial registration
NCT02268487.