bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel genetic loci, lifestyle factors, and inflammatory markers identified as risk factors for sarcoidosis
Authors: Yuan Shuai , Chen Jie , Zhao Sizheng Steven , Yarmolinsky James , Arkema Elizabeth , Tsilidis Konstantinos , Burgess Stephen , Larsson Susanna 
Published: March 2024

Abstract
We carried out a genome-wide association and Mendelian randomization analysis to probe genetic and environmental risk factors for sarcoidosis. We performed a genome-wide meta-analysis in 5,194 sarcoidosis cases and 777,559 non-cases from the FinnGen and UK Biobank studies. We estimated the heritability, pinpointed genomic risk loci, predicted deleteriousness, mapped corresponding genes, and enriched gene expression to tissues using FUMA (Functional Mapping and Annotation) and MAGMA (Multi-marker Analysis of GenoMic Annotation) softwares. We performed Mendelian randomization analyses to investigate the links between 6 modifiable factors and 66 inflammatory markers in relation to sarcoidosis. Genetic variants associated with these exposures at the genome-wide significance level and in low linkage disequilibrium were used as instrumental variables. The heritability of sarcoidosis explained by common genetic variants was around 12%. We annotated 14 genomic loci that surpassed the genome-wide significance threshold of which 6 loci were previously unreported. The locus proximal to TYK2 had a high potential deleterious impact on protein function. MAGMA revealed notable gene expression patterns in whole blood, spleen, and lung. Genetically predicted lower levels of physical activity and higher levels of body mass index, interleukin-23 receptor, and interleukin 1 receptor-like 2 were associated with a heighted risk of sarcoidosis.
The role of minocycline in inhibiting the formation of glial scars through the expression of CNTF, TGF-β1, and NF-κB p65 in traumatic brain injury model rats
Authors: Wardhana Donny Wisnu , Khotimah Husnul , Nazwar Tommy Alfandy , Nurdiana Nurdiana 
Published: March 2024

Abstract

Objective Traumatic brain injury (TBI) is one of the causes of permanent disability. The formation of glial scar after TBI is thought to be a contributing factor to this permanent disability. Currently, there is no effective therapy and research is being conducted to find neuroprotectant therapy in TBI, it is proven that one of the drugs that has potential as a neuroprotectant is minocycline. With different target organs and diseases, minocycline can inhibit CNTF, TGF-β1, and NF-κB p65 which contribute to the formation of glial scar. Therefore, this study aims to determine the role of minocycline in inhibiting glial scar formation through CNTF, TGF-β1, and NF-κB p65 pathways in TBI rats.
Methods A total of 16 rats were randomly divided into four groups: TBI, TBI + MNO1, TBI + MNO2, and TBI + MNO3. On day 0, rats were exposed to brain injury with a weight drop model, then treated with minocycline orally for 14 days, and observed for cognitive function through Novel Object Recognition (NOR) test on day 15. On the next day, the rats were decapitated, and the brain was taken for immunofluorescence double staining. The determination of signaling pathways was performed by observing immunofluorescence double staining of CNTF, TGF-β1, and NF-κB p65 in perilesional areas containing glial scar using a Confocal Laser Scanning Microscope (CLSM).
Results Administration of minocycline in TBI rats with a weight drop model can improve cognitive disorders after 14 days. The mechanism of minocycline in inhibiting glial scar formation is characterized by a decrease in GFAP intensity in the perilesion area of the brain through CNTF and TGF-β1 signaling pathways at doses of 50 mg/kg and 100 mg/kg orally. Although NF-κB p65 is not inhibited by minocycline specifically, NF-κB p65 interacting with CNTF and TGF-β1 plays a role in the mechanism of glial scar inhibition by minocycline. Inhibition of glial scar formation by minocycline promotes a permissive environment for axon regeneration, resulting in cognitive improvement after day 14.
Conclusion Minocycline plays a role in inhibiting glial scar formation through CNTF and TGF-β1 pathways in TBI model rats.
Strengthening crisis resilience in German primary care by using quality indicators: Findings of a process evaluation in the RESILARE project
Authors: Poß-Doering Regina , Koetsenrujiter Jan , Litke Nicola Alexandra , Weis Aline , Köppen Martina , Kümmel Stephanie , Szecsenyi Joachim , Wensing Michel 
Published: March 2024

Abstract

Background: In recent years, health systems worldwide were confronted with several crises such as natural disasters or the Covid-19 pandemic that affected lives and health of many people. In light of occurring waves of infections and heat, climate change is considered to be the biggest health threat of the 21st century. Strengthening individual and organizational crisis resilience in healthcare settings thus becomes a crucial factor in maintaining care quality and protecting vulnerable patients during such crises. The project RESILARE therefore aimed to develop and evaluate quality indicators which support primary care practices in preparing for and adapting to crisis-related challenges.
Methods: In a three-phased process, indicator development was based on systematic literature research and qualitative data, a two-stage expert panel process, and a pilot testing in a maximum of n=35 ambulatory practices during an outreach visit. Practice-individual indicator-related status and benchmarking were provided via feedback reports to complete the audit and feedback program. A mixed-methods process evaluation used semi-structured interviews with participating General Practitioners and non-physician health professionals to explore support and challenges for implementation of the derived set of quality indicators. Two online surveys were conducted to evaluate all indicators and the two-part feedback report. Qualitative data were analyzed inductively using a Thematic Analysis approach. Survey data were analyzed descriptively.
Results: A total of n=32 indicators covered four domains: (1) Individual Resilience, (2) Crisis Prevention, (3) Organizational Resilience, and (4) Climate Resilience. N=34 practices participated in the piloting and the process evaluation. Participants generally attributed a high relevance to the domains, and considered the indicator set to be suitable for implementation into existing quality management systems. Planning and implementation of measures that strengthen crisis resilience in practices were triggered or intensified by piloting the indicators and by the two-part feedback report. Identified challenges referred to the volume of indicators and to practice-individual implementation of the use of renewable energy sources in rented premises. Participants expressed their desire for peer exchange regarding proven concepts for crisis resilience.
Conclusion: The RESILARE quality indicators can strengthen crisis resilience and ecologically sustainable processes in primary care practices. Implementation into quality management systems should heed identified potential challenges to avoid overstraining of practices.
Untargeted Metabolomics Reveals Fruit Secondary Metabolites Alter Bat Nutrient Absorption
Authors: GELAMBI MARIANA , WHITEHEAD SUSAN R. 
Published: March 2024

Abstract
The ecological interaction between fleshy fruits and frugivores is influenced by diverse mixtures of secondary metabolites that naturally occur in the fruit pulp. Although some fruit secondary metabolites have a primary role in defending the pulp against antagonistic frugivores, these metabolites also potentially affect mutualistic interactions. The physiological impact of these secondary metabolites on mutualistic frugivores remains largely unexplored. Using a mutualistic fruit bat (Carollia perspicillata), we showed that ingesting four secondary metabolites commonly found in plant tissues affects bat foraging behavior and induces changes in the fecal metabolome. Our behavioral trials showed that the metabolites tested typically deter bats. Our metabolomic surveys suggest that secondary metabolites alter, either by increasing or decreasing, the absorption of essential macronutrients, including carbohydrates and lipids. These behavioral and physiological effects vary based on the specific identity and concentration of the metabolite tested. Our results also suggest that a portion of the secondary metabolites consumed is excreted by the bat intact or slightly modified. By identifying key shifts in the fecal metabolome of a mutualistic frugivore caused by secondary metabolite consumption, this study improves our understanding of the effects of fruit chemistry on frugivore physiology.
Real World Community-Based HIV Rapid Start Antiretroviral with B/F/TAF versus Conventional HIV Antiretroviral Therapy Start – The RoCHaCHa Study, A Pilot Study
Authors: Valenti William , Scutaru Jacob , Mancenido Michael , Zuppelli Ashley , Danforth Alexandra , Corales Roberto , Hilliard Shealynn 
Published: March 2024

Abstract
Background
The rapid start of antiretroviral therapy (RSA) model initiates antiretroviral therapy (ART) as soon as possible after a new or preliminary diagnosis of HIV, in advance of HIV-1 RNA and other baseline laboratory testing. This observational study aims to determine if RSA with a single tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) is an effective regimen for achieving viral suppression and accepted by patients at the time of diagnosis.
Methods
Adults newly or preliminarily diagnosed with HIV were enrolled from October 2018 through September 2021. Real world advantage, measured in days between clinical milestones and time to virologic suppression, associated with B/F/TAF RSA was compared to historical controls.
Results
All Study RSA participants (n = 45) accepted treatment at their first visit and 43(95.6%) achieved virologic suppression by week 48. Study RSA participants had a significantly shorter time (median 32 days) from diagnosis to ART initiation and virologic suppression, in comparison to historical controls (median 181 days) (n = 42). Qualitative feedback from study RSA participants showed high acceptance positive response to RSA.
Conclusions
RSA is feasible and well accepted by patients in a real-world community-based clinic setting. Promoting RSA in community-based clinics is an important tool in ending the HIV epidemic.
The effect of a sub-classification of pediatric Gartland type Ⅲ on determining the prognosis of supracondylar humerus fractures and treatment modality.
Authors: Qiao Yusen , Zhao Xue-quan , Xixi Han , Haifu Sun , Yongben Li , Bin Zhao , Yao Shuzhang 
Published: March 2024

Abstract
Background
The new Gartland classification of supracondylar humeral fractures was based on fracture location and displacement. However, incarcerated supracondylar humerus fractures were not considered. The new sub-classification is Gartland Ⅲ C. This paper explains the theory and methods of this classification.
Methods
In this study, we included all patients with Gartland Ⅲ C who underwent surgery between January 2019 and January 2023. The patients were divided into two groups according to surgical treatment. One patient underwent closed reduction and internal fixation (Group A), whereas the other underwent open reduction and internal fixation (Group B). The Baumann angle, final Flynn scores, and malformations were evaluated in both groups.
Results
We include 56 patients with a mean age of 6.96 years (4–12 years). The chosen treatments were 34 closed reduction and internal fixation (Group A) and 22 open reduction and internal fixation (Group B). The difference in fracture healing time between the two groups was not statistically significant. At 6 months postoperatively, group B had a smaller robust Baumann angle than group A. The Flynn grade of elbow function at the last follow-up was better in group B than in group A. The postoperative review showed coronal and sagittal deformities were smaller in group B than in group A.
Conclusions
Completely displaced Gartland Ⅲ C fractures treated using open reduction and internal fixation have a lower risk of complications than those treated using closed reduction and internal fixation. We propose the sub-classification of Gartland IIIC for this type of fracture.
Multilevel barriers to guideline implementation - a nationwide multi- professional cross- sectional study within child and adolescent psychiatry
Authors: Santesson Anna Helena Elisabeth , Holmberg Robert , Bäckström Martin , Gustafsson Peik , Perrin Sean , Jarbin Håkan 
Published: March 2024

Abstract

Background
Despite efforts to promote guideline use, guideline adoption is often suboptimal due to failure to identify and address relevant barriers. Barriers vary not only between guidelines but also between settings, intended users, and targeted patients. Multi-professional guidelines are often used in child and adolescent mental health services (CAMHS), making the implementation process more difficult. Despite this, there is a lack of knowledge about which barriers to consider or if barriers vary by profession. The aim of this study was to address these gaps by examining barriers to adopting a multi-professional depression guideline in the context of a nationwide implementation study.
Methods
440 CAMHS clinicians across Sweden (52%) completed the Barriers and Facilitators Assessment Instrument (BFAI) ahead of an implementation endeavour. BFAI is a widely used and validated measure of guideline implementation on four scales: Innovation, Provider, Context, and Patient. Barriers were calculated at scale and at item levels. ANOVA and chi-square tests were used to analyse differences by profession and effect sizes were calculated.
Results
Overall, clinicians were optimistic about guideline uptake, particularly about guideline characteristics and own adoption abilities. Barriers were related to the patient and the context domains, as well as individual clinician knowledge and training. Perceptions differed across professions; psychiatrists were most, and counsellors were least positive about guideline embeddedness.
Conclusion
This large-scale quantitative study suggests that CAMHS clinicians have an overall favourable attitude towards guideline adoption but highlight the need for adaptations to certain patient groups. Strategies to improve guideline use should primarily address these patient issues while securing proper support. Implementation efforts, particularly those targeting staff knowledge, training, and involvement, may benefit from being tailored to different professional needs. These findings may inform implementation projects in CAMHS and future research.
The Role of Family Support in Entrepreneurial Endeavors: Perspectives from Family-Owned Businesses
Authors: Dewi Lutfiana 
Published: March 2024

Abstract
This qualitative research explores the multifaceted dynamics of family support within the context of entrepreneurial ventures, with a specific focus on family-owned businesses. Through in-depth interviews and thematic analysis, the study investigates the experiences, perceptions, and challenges faced by entrepreneurs in navigating the intricate interplay between familial relationships and business pursuits. The findings highlight the pivotal role of family support in shaping entrepreneurial journeys, influencing decision-making processes, fostering resilience, and sustaining long-term success. Emotional support emerges as a central theme, with participants emphasizing the importance of encouragement, understanding, and empathy from family members. Financial support from family members is also identified as crucial, providing entrepreneurs with the resources and stability needed to pursue their business ventures. Decision-making dynamics within family-owned businesses reflect the complexities of balancing familial relationships with business objectives, while generational transitions represent a critical juncture in the lifecycle of family enterprises, with implications for continuity, innovation, and identity preservation. The study underscores the importance of understanding the nuances of family support dynamics for fostering synergy and facilitating the sustainable growth of family-owned enterprises. By illuminating the complexities and challenges inherent in family relationships and their impact on entrepreneurial outcomes, the research contributes to a deeper understanding of the role of family in entrepreneurship. Moving forward, further research and practical interventions aimed at enhancing family cohesion, communication, and governance structures can contribute to the resilience and sustainability of family-owned businesses in an increasingly dynamic and competitive business landscape.
Optimized protocol for collecting root canal biofilms for in vitro studies
Authors: Goulart Rafael da Silva , Oliveira-Silva Mariana , Silva-Sousa Yara Teresinha Correa , Miranda Carlos Eduardo Saraiva , Pitondo-Silva André 
Published: March 2024

Abstract

Aim
The goal of this study was to standardize a new protocol for collecting biofilm from the interior of the root canal system (RCS) for in vivo testing.
Methodology:
In this study, 44 bovine incisors were used. The samples were divided into three experimental groups: 14 teeth, 12 for counting colony-forming units (CFU), and two samples for scanning electron microscopy (SEM). The first group was used for the biofilm collection protocol proposed here, the second group for the 2nd Biofilm Collection Protocol collection, and the third group for biofilm collection with an absorbent paper tip. Two additional teeth were used as sterilization controls to ensure that the experiments were free of contamination. The coronal region was removed and standardized at 15 mm. They were fitted with a Protaper up to the F5 insert, and the apical foramen was sealed with composite resin. The roots were stabilized with acrylic resin in a 1.5 mL Eppendorf tube. The specimens were sterilized and then inoculated with Enterococcus faecalis NTCT 775 every 24 h for 21 days. Following the period, each group underwent biofilm collection protocols, and CFU and scanning electron microscopy (SEM) data were analyzed. Shapiro–Wilk and one-way ANOVA tests were used to determine statistically significant differences between groups.
Results
The biofilm collection protocol group had the most CFUs, with extremely high values when compared with the other groups when converted to Log10. The results of the One-Way ANOVA test revealed that the 2nd collection protocol and absorbent paper tip collection groups were statistically similar (p > 0.05), whereas the biofilm collection protocol group was not.
Conclusion
The biofilm collection protocol proposed in this study was effective at collecting microorganisms from within the RCS. Compared to the biofilm collection protocol with paper cones, the in vivo collection protocol from bovine teeth yielded significantly more CFUs. Thus, the proposed protocol significantly increases the bacterial load of biofilms collected from the RCS sample, bringing the experiments closer to the reality of endodontic infections.
Optimal parameters of protection devices for controlling hydraulic transient using genetic algorithms
Authors: Alhwij Mohammed Salah , Nakhleh Wissam 
Published: March 2024

Abstract

Air valves and pressure vessels are among the most important protection devices used to protect the main pumping lines due to their reliability in controlling transient pressures. The proper and rational design of the water hammer protection devices ensures high efficiency in controlling the values of transient pressures in addition to achieving acceptable cost. For this purpose, the genetic algorithm approach was adopted in the process of selecting the optimal parameters for both pressure vessels (size and orifice diameter) and air valves (orifice diameter of inlet and outlet, discharge coefficients of inlet and outlet) in addition to determining the type and location of the air valve. The performance of the proposed protection devices was verified by comparing three objective equations: (1) minimizing the cost of protection devices, (2) minimizing the difference between the maximum and minimum pressure, and (3) minimizing the difference between the maximum and minimum pressure with a specific constraint on the budget of protection devices. The study results showed that selecting the optimal design parameters for pressure vessels and air valves helps control the cost of protection devices and transient pressure values.
Pharmacological Mechanisms of Kirenol against Ovarian Carcinoma:
A Network Pharmacology and Experimental Validation Study In Vitro
Authors: Mao Xiaoling , Zhu Hong , Gao Jun , Lin Shixin , Bao Yin , Zhang Mingyue , Yang Huan 
Published: March 2024

Background:
Ovarian carcinoma is an aggressive gynecological malignancy. Kirenol,
a diterpene compound, has recently gained attention for its potential anticancer properties. However,
its exact anti-tumor mechanism remains largely unexplored.

Objective:
In this study, we explored the inhibitory effects of Kirenol on ovarian cancer using
network pharmacology and in vitro experiments and elucidated its underlying mechanisms.

Methods:
Through the utilization of molecular docking, we established a network of proteinprotein
interactions (PPI), which unveiled CDK4 as an essential target. Additionally, gene enrichment
and pathway analysis highlighted the significance of the PI3K/AKT pathway. The viability
of ovarian cancer cells and normal ovarian epithelial cells was evaluated using CCK8 assays
to determine the effect of Kirenol. Following in vitro tests, cell colony formation, wound
healing, flow cytometry, and Western blotting were conducted to assess its impact on cell proliferation,
metastasis, apoptosis, and the cell cycle.

Results:
Kirenol significantly reduced the viability of ovarian cancer cells (SKOV3 and A2780)
compared to normal ovarian epithelial cells (IOSE-80). Moreover, Kirenol efficiently suppressed
the growth and movement, caused a cell cycle halt, and stimulated programmed cell death in
SKOV3 and A2780 cells. Through molecular analysis, it was observed that Kirenol increased
the expression of Bax while decreasing the expression of MMP2, MMP9, and Bcl-2. It also attenuated
the phosphorylation of PI3K, AKT, and RB and downregulated CDK4 and CCND1 expression.
Notably, co-treatment with the PI3K pathway inhibitor LY294002 enhanced the inhibitory
effect of Kirenol on ovarian cancer cells.

Conclusion:
In summary, the combined results of our network pharmacology analysis and in
vitro tests emphasized that Kirenol hinders the growth of ovarian cancer cells, causes cell cycle
arrest, enhances apoptosis, and hampers migration, possibly by regulating the PI3K/AKT/CDK4
signaling pathway.
Advances in the Synthesis and Bioactivity of Polysaccharide Selenium
Nanoparticles: A Review
Authors: Ye Shiying , Sun Shaowei , Cai Jiye , Jiang Jinhuan 
Published: March 2024

Abstract:
Selenium, an essential trace element of the human body, is pivotal in human health and
disease prevention. Nevertheless, the narrow therapeutic index of selenium, where the toxic and
therapeutic doses are close, limits its clinical utility. Significantly, nanoscale selenium synthesized
by different methods using polysaccharides as stabilizers has low toxicity properties and exhibits
excellent bioactivity. Its biological activities, such as anti-tumor, anti-inflammatory, antioxidant,
antibacterial, and immune function enhancement, are improved compared with traditional organic
and inorganic selenium compounds, conferring greater potential for application in biomedicine.
Therefore, this review evaluates the advancements in various synthesis methodologies for polysaccharide
selenium nanoparticles (Se NPs) and their biological activities. It aims to provide a comprehensive
theoretical basis and research directions for the future development of highly efficient, minimally
toxic, and biocompatible polysaccharide-Se NPs and the application of polysaccharide-Se
NPs in biomedicine.