bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircPRKD3/miR-6783-3p responds to mechanical force to facilitate the osteogenesis of stretched periodontal ligament stem cells
Authors: Liu Jiani , Liu Rui , Wang Hong , Zhang Zijie , Wang Jixiao , Wei Fulan 
Published: April 2024

Abstract
Background
The mechanotransduction mechanisms by which cells regulate tissue remodeling are not fully deciphered. Circular RNAs (circRNAs) are crucial to various physiological processes, including cell cycle, differentiation, and polarization. However, the effects of mechanical force on circRNAs and the role of circRNAs in the mechanobiology of differentiation and remodeling in stretched periodontal ligament stem cells (PDLSCs) remain unclear. This article aims to explore the osteogenic function of mechanically sensitive circular RNA protein kinase D3 (circPRKD3) and elucidate its underlying mechanotransduction mechanism.

Materials and methods
PDLSCs were elongated with 8% stretch at 0.5 Hz for 24 h using the Flexcell® FX-6000™ Tension System. CircPRKD3 was knockdown or overexpressed with lentiviral constructs or plasmids. The downstream molecules of circPRKD3 were predicted by bioinformatics analysis. The osteogenic effect of related molecules was evaluated by quantitative real-time PCR (qRT‐PCR) and western blot.

Results
Mechanical force enhanced the osteogenesis of PDLSCs and increased the expression of circPRKD3. Knockdown of circPRKD3 hindered PDLSCs from osteogenesis under mechanical force, while overexpression of circPRKD3 promoted the early osteogenesis process of PDLSCs. With bioinformatics analysis and multiple software predictions, we identified hsa-miR-6783-3p could act as the sponge of circPRKD3 to indirectly regulate osteogenic differentiation of mechanically stimulated PDLSCs.

Conclusions
Our results first suggested that both circPRKD3 and hsa-miR-6783-3p could enhance osteogenesis of stretched PDLSCs. Furthermore, hsa-miR-6783-3p could sponge circPRKD3 to indirectly regulate RUNX2 during the periodontal tissue remodeling process in orthodontic treatment.
Robotic-assisted plate fixation of the anterior acetabulum - clinical description of a new technique
Authors: Kabir Koroush , von Rundstedt Friedrich-Carl , Roos Jonas , Gathen Martin 
Published: April 2024

Abstract
Introduction
We present a detailed procedure for the robotic-assisted plate osteosynthesis of an anterior acetabular fracture. The purpose of this work was to describe a robotic-assisted minimally invasive technique as a possible method for reducing complications, pain, and hospitalization. Another goal was to present technical recommendations and to assess potential pitfalls and problems of the new surgical approach.

Methods
Surgery was performed in an interdisciplinary setting by an experienced orthopedic surgeon and a urologist. The DaVinci System with standard instruments was used. Reduction was achieved through indirect traction of a pin that was introduced into the femoral neck and direct manipulation via the plate. The plate position and fixation were achieved through 7 additional minimally invasive incisions.

Results
The technique has multiple advantages, such as no detachment of the rectus abdominal muscle, a small skin incision, and minimal blood loss. Furthermore, this approach might lower the incidence of hernia formation, infection, and postoperative pain.

Discussion
We see the presented technique as a demanding yet progressive and innovative surgical method for treating acetabular fractures with indications for anterior plate fixation.

Trial registration
The study was approved by the local institutional review board (Nr. 248/18).
Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms
Authors: Mohammadzadeh Mahsa , Zarei Masoud , Abbasi Hossein , Webster Thomas J. , Beheshtizadeh Nima 
Published: April 2024

AbstractThere is an increasing demand for innovative strategies that effectively promote osteogenesis and enhance bone regeneration. The critical process of bone regeneration involves the transformation of mesenchymal stromal cells into osteoblasts and the subsequent mineralization of the extracellular matrix, making up the complex mechanism of osteogenesis. Icariin’s diverse pharmacological properties, such as anti-inflammatory, anti-oxidant, and osteogenic effects, have attracted considerable attention in biomedical research. Icariin, known for its ability to stimulate bone formation, has been found to encourage the transformation of mesenchymal stromal cells into osteoblasts and improve the subsequent process of mineralization. Several studies have demonstrated the osteogenic effects of icariin, which can be attributed to its hormone-like function. It has been found to induce the expression of BMP-2 and BMP-4 mRNAs in osteoblasts and significantly upregulate Osx at low doses. Additionally, icariin promotes bone formation by stimulating the expression of pre-osteoblastic genes like Osx, RUNX2, and collagen type I. However, icariin needs to be effectively delivered to bone to perform such promising functions.Encapsulating icariin within nanoplatforms holds significant promise for promoting osteogenesis and bone regeneration through a range of intricate biological effects. When encapsulated in nanofibers or nanoparticles, icariin exerts its effects directly at the cellular level. Recalling that inflammation is a critical factor influencing bone regeneration, icariin's anti-inflammatory effects can be harnessed and amplified when encapsulated in nanoplatforms. Also, while cell adhesion and cell migration are pivotal stages of tissue regeneration, icariin-loaded nanoplatforms contribute to these processes by providing a supportive matrix for cellular attachment and movement. This review comprehensively discusses icariin-loaded nanoplatforms used for bone regeneration and osteogenesis, further presenting where the field needs to go before icariin can be used clinically.
Rapidly improving ARDS differs clinically and biologically from persistent ARDS
Authors: Valda Toro Patricia L. , Willmore Andrew , Wu Nelson E. , Delucchi Kevin L. , Jauregui Alejandra , Sinha Pratik , Liu Kathleen D. , Hendrickson Carolyn M. , Sarma Aartik , Neyton Lucile P. A. , Leligdowicz Aleksandra , Langelier Charles R. , Zhuo Hanjing , Jones Chayse , Kangelaris Kirsten N. , Gomez Antonio D. , Matthay Michael A. , Calfee Carolyn S. 
Published: April 2024

Abstract
Background
Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes.

Methods
We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO2:FiO2 > 300 or (ii) SpO2: FiO2 > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described.

Results
RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001).

Conclusions
This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials.
Screening mammography performance according to breast density: a comparison between radiologists versus standalone intelligence detection
Authors: Kwon Mi-ri , Chang Yoosoo , Ham Soo-Youn , Cho Yoosun , Kim Eun Young , Kang Jeonggyu , Park Eun Kyung , Kim Ki Hwan , Kim Minjeong , Kim Tae Soo , Lee Hyeonsoo , Kwon Ria , Lim Ga-Young , Choi Hye Rin , Choi JunHyeok , Kook Shin Ho , Ryu Seungho 
Published: April 2024

Abstract
Background
Artificial intelligence (AI) algorithms for the independent assessment of screening mammograms have not been well established in a large screening cohort of Asian women. We compared the performance of screening digital mammography considering breast density, between radiologists and AI standalone detection among Korean women.

Methods
We retrospectively included 89,855 Korean women who underwent their initial screening digital mammography from 2009 to 2020. Breast cancer within 12 months of the screening mammography was the reference standard, according to the National Cancer Registry. Lunit software was used to determine the probability of malignancy scores, with a cutoff of 10% for breast cancer detection. The AI’s performance was compared with that of the final Breast Imaging Reporting and Data System category, as recorded by breast radiologists. Breast density was classified into four categories (A–D) based on the radiologist and AI-based assessments. The performance metrics (cancer detection rate [CDR], sensitivity, specificity, positive predictive value [PPV], recall rate, and area under the receiver operating characteristic curve [AUC]) were compared across breast density categories.

Results
Mean participant age was 43.5 ± 8.7 years; 143 breast cancer cases were identified within 12 months. The CDRs (1.1/1000 examination) and sensitivity values showed no significant differences between radiologist and AI-based results (69.9% [95% confidence interval [CI], 61.7–77.3] vs. 67.1% [95% CI, 58.8–74.8]). However, the AI algorithm showed better specificity (93.0% [95% CI, 92.9–93.2] vs. 77.6% [95% CI, 61.7–77.9]), PPV (1.5% [95% CI, 1.2–1.9] vs. 0.5% [95% CI, 0.4–0.6]), recall rate (7.1% [95% CI, 6.9–7.2] vs. 22.5% [95% CI, 22.2–22.7]), and AUC values (0.8 [95% CI, 0.76–0.84] vs. 0.74 [95% CI, 0.7–0.78]) (all P < 0.05). Radiologist and AI-based results showed the best performance in the non-dense category; the CDR and sensitivity were higher for radiologists in the heterogeneously dense category (P = 0.059). However, the specificity, PPV, and recall rate consistently favored AI-based results across all categories, including the extremely dense category.

Conclusions
AI-based software showed slightly lower sensitivity, although the difference was not statistically significant. However, it outperformed radiologists in recall rate, specificity, PPV, and AUC, with disparities most prominent in extremely dense breast tissue.
The clinical value of mNGS of bronchoalveolar lavage fluid versus traditional microbiological tests for pathogen identification and prognosis of severe pneumonia (NT-BALF):study protocol for a prospective multi-center randomized clinical trial
Authors: Song Xiao , Jiang Hui , Zong Liang , Shi Di , Zhu Huadong 
Published: April 2024

Abstract
Background
Early, rapid, and accurate pathogen diagnosis can help clinicians select targeted treatment options, thus improving prognosis and reducing mortality rates of severe pneumonia. Metagenomic next-generation sequencing (mNGS) has a higher sensitivity and broader pathogen spectrum than traditional microbiological tests. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes and cost-effectiveness in patients with severe pneumonia have not been evaluated.

Methods
This is a regional, multi-center, open, prospective, randomized controlled trial to evaluate that whether the combination of mNGS and traditional testing methods could decrease 28-day call-cause mortality with moderate cost-effectiveness. A total of 192 patients with severe pneumonia will be recruited from four large tertiary hospitals in China. Bronchoalveolar lavage fluid will be obtained in all patients and randomly assigned to the study group (mNGS combined with traditional microbiological tests) or the control group (traditional microbiological tests only) in a 1:1 ratio. Individualized antimicrobial treatment and strategy will be selected according to the analysis results. The primary outcome is 28-day all-cause mortality. The secondary outcomes are ICU and hospital length of stay (LOS), ventilator-free days and ICU-free days, consistency between mNGS and traditional microbiological tests, detective rate of mNGS and traditional microbiological tests, turn-out time, time from group allocation to start of treatment, duration of vasopressor support, types and duration of anti-infective regimens, source of drug-resistant bacteria or fungi, and ICU cost.

Discussion
The clinical benefits of mNGS are potentially significant, but its limitations should also be considered.

Trial registration
ChineseClinicalTrialRegistry.org, ChiCTR2300076853. Registered on 22 October 2023.
Sex differences of post-Covid patients undergoing outpatient pulmonary rehabilitation
Authors: Kautzky Alexander , Nopp Stephan , Gattinger Dietlinde , Petrovic Milos , Antlinger Martin , Schomacker Dustin , Kautzky-Willer Alexandra , Zwick Ralf Harun 
Published: April 2024

Abstract
Background
Following years of pandemic severe acute respiratory syndrome coronavirus 2 infections labelled Covid-19, long lasting impairment summarized as post-Covid syndrome (PCS) challenges worldwide healthcare. Patients benefit from rehabilitation programs, but sex specific aspects of improvement remain little understood. The aim of the study was to assess whether women and men differ in response to outpatient pulmonary rehabilitation for PCS.

Methods
263 (54.4% female) patients partaking in outpatient pulmonary rehabilitation (OPR) due to PCS between March 2020 and July 2022 were included in a prospective observational cohort study. Outcomes were assessed at baseline and before discharge from OPR and included six-minute walking distance (6MWD), 1-second forced expiratory volume (FEV1), diffusion capacity for carbon monoxide, maximal inspiratory pressure (MIP), dyspnea (medical research council scale), and post-Covid functional status scale (PCFS). Sexspecific changes in outcomes following OPR were assessed by linear mixed model and presented as mean differences (MD) with 95% confidence intervals. Linear regression was applied to test whether 6MWD correlates with PCFS and the minimal clinically important difference (MCID) in 6MWD regarding an improvement of at least one point in PCFS was computed with logistic regression.

Results
Significant improvement throughout OPR was observed for all outcomes (all p < 0.0001). Despite less severe Covid-19 infections, PCFS scores remained higher in females after OPR (p = 0.004) and only 19.4% of women compared to 38.5% of men achieved remission of functional impairment. At baseline as well as after OPR, females showed higher symptom load compared to men in dyspnea (p = 0.0027) and scored lower in FEV1 (p = 0.009) and MIP (p = 0.0006) assessment. Performance in 6MWD was comparable between men and women. An increase of 35 m in 6MWD was computed as minimal clinically important difference to improve functional impairment.

Conclusion
Both subjective symptoms such as fatigue and dyspnea and objective impairment in performance in pulmonary function were more frequently observed among women. Despite improvement throughout OPR in both women and men, the sex-gap in symptom load could not be closed as women less often achieved remission from functional impairment due to PCS. Intensified treatment of these symptoms should be considered in women undergoing rehabilitation for PCS.
Meeting the challenges of the 21st century: the fundamental importance of trust for transformation
Authors: McKee Martin , van Schalkwyk May CI , Greenley Rachel 
Published: April 2024

Abstract
Background
This paper is one of a collection on challenges facing health systems in the future. One obvious challenge is how to transform to meet changing health needs and take advantage of emerging treatment opportunities. However, we argue that effective transformations are only possible if there is trust in the health system.

Main body
We focus on three of the many relationships that require trust in health systems, trust by patients and the public, by health workers, and by politicians. Unfortunately, we are seeing a concerning loss of trust in these relationships and, for too long, the importance of trust to health policymaking and health system functioning has been overlooked and under-valued. We contend that trust must be given the attention, time, and resources it warrants as an indispensable element of any health system and, in this paper, we review why trust is so important in health systems, how trust has been thought about by scholars from different disciplines, what we know about its place in health systems, and how we can give it greater prominence in research and policy.

Conclusion
Trust is essential if health systems are to meet the challenges of the 21st century but it is too often overlooked or, in some cases, undermined.
Meta-analysis of the global distribution of clinically relevant CYP2C8 alleles and their inferred functional consequences
Authors: Camara Mahamadou D. , Zhou Yitian , De Sousa Taís Nóbrega , Gil José P. , Djimde Abdoulaye A. , Lauschke Volker M. 
Published: April 2024

Abstract
Background
CYP2C8 is responsible for the metabolism of 5% of clinically prescribed drugs, including antimalarials, anti-cancer and anti-inflammatory drugs. Genetic variability is an important factor that influences CYP2C8 activity and modulates the pharmacokinetics, efficacy and safety of its substrates.

Results
We profiled the genetic landscape of CYP2C8 variability using data from 96 original studies and data repositories that included a total of 33,185 unrelated participants across 44 countries and 43 ethnic groups. The reduced function allele CYP2C8*2 was most common in West and Central Africa with frequencies of 16–36.9%, whereas it was rare in Europe and Asia (< 2%). In contrast, CYP2C8*3 and CYP2C8*4 were common throughout Europe and the Americas (6.9–19.8% for *3 and 2.3–7.5% for *4), but rare in African and East Asian populations. Importantly, we observe pronounced differences (> 2.3-fold) between neighboring countries and even between geographically overlapping populations. Overall, we found that 20–60% of individuals in Africa and Europe carry at least one CYP2C8 allele associated with reduced metabolism and increased adverse event risk of the anti-malarial amodiaquine. Furthermore, up to 60% of individuals of West African ancestry harbored variants that reduced the clearance of pioglitazone, repaglinide, paclitaxel and ibuprofen. In contrast, reduced function alleles are only found in < 2% of East Asian and 8.3–12.8% of South and West Asian individuals.

Conclusions
Combined, the presented analyses mapped the genetic and inferred functional variability of CYP2C8 with high ethnogeographic resolution. These results can serve as a valuable resource for CYP2C8 allele frequencies and distribution estimates of CYP2C8 phenotypes that could help identify populations at risk upon treatment with CYP2C8 substrates. The high variability between ethnic groups incentivizes high-resolution pharmacogenetic profiling to guide precision medicine and maximize its socioeconomic benefits, particularly for understudied populations with distinct genetic profiles.
Falling and rising in the vortex of cancer: children’s adaptation with cancer: a qualitative study
Authors: Sepahvand Fatemeh , Valizadeh Fatemeh , Karami Kimia , Abdolkarimi Babak , Ghasemi Fatemeh 
Published: April 2024

Abstract
Background
Cancer is a considerable health problem worldwide and the second leading cause of death in children. It has many physical, psychological, and social consequences for children and their families. The ability to adapt to cancer plays a vital role in the recovery and quality of life of affected children. This study aimed to explain the adaptation of children with cancer to their disease.

Methods
This qualitative study adopted the directed content analysis approach based on the Roy nursing model. The participants were nine children with cancer aged 6–18 years old, five family members, four nurses, one doctor, one teacher, and two charity association members, recruited by purposive sampling method. The information was collected via individual semi-structured interviews, a focus group discussion, and field notes. The data were analyzed simultaneously with data collection using the Elo and Kyngäs method. The study rigor was ensured based on the Guba and Lincoln criteria.

Findings
Of the four categories of physical challenges, fragile self-concept, the difficulty of role transition, and disruption of the path to independence, the theme of Falling and rising in the cancer vortex was abstracted.

Conclusion
Based on the Roy model, the children in the present study were at the compensatory level of adaptation. This research demonstrates that the adaptation of children being treated for cancer is fragile and not constant. With each hospitalization and exacerbation of the disease, they made efforts to adapt to their disease using regulatory and cognitive subsystems. Paying attention to different stimulants and the effects of support systems on physical challenges, fragile self-concept, difficult role transition, and disruption of the path to independence for each child, as well as providing individualized care for these children, can help their adaptation to and healthy transition from the vortex of cancer. The Roy adaptation model was helpful and efficient for elucidating the adaptation of children with cancer. Providing care for children by healthcare specialists, especially nurses, should be theory-based and individualized.