bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of on-site Supportive Communication Training (On-site SCT) on doctor-patient communication in oncology: Study protocol of a randomized, controlled mixed-methods trial
Authors: KK Antonsen , AT Johnsen , LØ Poulsen , JD Lyhne , L Lund , S Eßer-Naumann , S Timm , LH Jensen 
Published: May 2024

Abstract
Background
The quality of communication in oncology significantly impacts patients' health outcomes, as poor communication increases the risk of unnecessary treatment, inadequate pain relief, higher anxiety levels, and acute hospitalizations. Additionally, ineffective communication skills training (CST) is associated with stress, low job satisfaction, and burnout among doctors working in oncology. While acknowledging the importance of effective communication, the specific features of successful CST remain uncertain. Role-play and recorded consultations with direct feedback appear promising for CST but may be time-consuming and face challenges in transferring acquired skills to clinical contexts. Our aim is to bridge this gap by proposing a novel approach: On-site Supportive Communication Training (On-site SCT). The concept integrates knowledge from previous studies but represents the first randomized controlled trial employing actual doctor-patient interactions during CST.

Methods
This randomized multicenter trial is conducted at three departments of oncology in Denmark. Doctors are randomized 1:1 to the intervention and control groups. The intervention group involves participation in three full days of On-site SCT facilitated by a trained psychologist. On-site SCT focuses on imparting communication techniques, establishing a reflective learning environment, and offering emotional support with a compassionate mindset. The primary endpoint is the change in percentage of items rated “excellent” by the patients in the validated 15-item questionnaire Communication Assessment Tool. The secondary endpoints are changes in doctors’ ratings of self-efficacy in health communication, burnout, and job satisfaction measured by validated questionnaires. Qualitative interviews will be conducted with the doctors after the intervention to evaluate its relevance, feasibility, and working mechanisms. Doctors have been actively recruited during summer/autumn 2023. Baseline questionnaires from patients have been collected. Recruitment of new patients for evaluation questionnaires is scheduled for Q1-Q2 2024.

Discussion
This trial aims to quantify On-site SCT efficacy. If it significantly impacts patients/doctors, it can be a scalable CST concept for clinical practice. Additionally, qualitative interviews will reveal doctors' insight into the most comprehensible curriculum parts.

Trial registration
April 2023 – ClinicalTrials.gov (NCT05842083). April 2023 – The Research Ethics Committee at the University of Southern Denmark (23/19397).
Analysis of onset-to-door time and its influencing factors in Chinese patients with acute ischemic stroke during the 2020 COVID-19 epidemic: a preliminary, prospective, multicenter study
Authors: Liao Yuqi , Qi Wenwei , Li Shuting , Shi Xin , Wu Xiaohong , Chi Feng , Xia Runyu , Qin Limin , Cao Liming , Ren Lijie 
Published: May 2024

Abstract
Background
Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors.

Methods
We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay.

Results
In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024–2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548–32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236–0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216–0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207–0.679), moderate stroke (OR: 0.644, 95% CI: 0.462–0.901), and severe stroke (OR: 0.506, 95% CI: 0.285–0.908).

Conclusions
Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints.
Contribution of extracellular vesicles for the pathogenesis of retinal diseases: shedding light on blood-retinal barrier dysfunction
Authors: Martins Beatriz , Pires Maria , Ambrósio António Francisco , Girão Henrique , Fernandes Rosa 
Published: May 2024

AbstractRetinal degenerative diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), loom as threats to vision, causing detrimental effects on the structure and function of the retina. Central to understanding these diseases, is the compromised state of the blood-retinal barrier (BRB), an effective barrier that regulates the influx of immune and inflammatory components. Whether BRB breakdown initiates retinal distress, or is a consequence of disease progression, remains enigmatic. Nevertheless, it is an indication of retinal dysfunction and potential vision loss.The intricate intercellular dialogues among retinal cell populations remain unintelligible in the complex retinal milieu, under conditions of inflammation and oxidative stress. The retina, a specialized neural tissue, sustains a ceaseless demand for oxygen and nutrients from two vascular networks. The BRB orchestrates the exchange of molecules and fluids within this specialized region, comprising the inner BRB (iBRB) and the outer BRB (oBRB). Extracellular vesicles (EVs) are small membranous structures, and act as messengers facilitating intercellular communication in this milieu.EVs, both from retinal and peripheral immune cells, increase complexity to BRB dysfunction in DR and AMD. Laden with bioactive cargoes, these EVs can modulate the retinal microenvironment, influencing disease progression. Our review delves into the multifaceted role of EVs in retinal degenerative diseases, elucidating the molecular crosstalk they orchestrate, and their microRNA (miRNA) content. By shedding light on these nanoscale messengers, from their biogenesis, release, to interaction and uptake by target cells, we aim to deepen the comprehension of BRB dysfunction and explore their therapeutic potential, therefore increasing our understanding of DR and AMD pathophysiology.
Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies
Authors: Rolver Monica G , Emanuelsson Frida , Nordestgaard Børge G , Benn Marianne 
Published: May 2024

Abstract
Objective
To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related.

Research design and methods
Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC.

Results
Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10− 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (−0.04 (−0.12, 0.32) and − 0.03 (−0.13, 0.06)), nor of glucose on CRP (−0.01 (−0.08, 0.07) and − 0.00 (−0.14, 0.13)).

Conclusions
Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.
Persistent inequities in maternal mortality in Latin America and the Caribbean, 1990–2019
Authors: Sáenz Rocío , Nigenda Gustavo , Gómez-Duarte Ingrid , Rojas Karol , Castro Arachu , Serván-Mori Edson 
Published: May 2024

Abstract
Background
Despite the resources and personnel mobilized in Latin America and the Caribbean to reduce the maternal mortality ratio (MMR, maternal deaths per 100 000 live births) in women aged 10–54 years by 75% between 2000 and 2015, the region failed to meet the Millenium Development Goals (MDGs) due to persistent barriers to access quality reproductive, maternal, and neonatal health services.

Methods
Using 1990–2019 data from the Global Burden of Disease project, we carried out a two-stepwise analysis to (a) identify the differences in the MMR temporal patterns and (b) assess its relationship with selected indicators: government health expenditure (GHE), the GHE as percentage of gross domestic product (GDP), the availability of human resources for health (HRH), the coverage of effective interventions to reduce maternal mortality, and the level of economic development of each country.

Findings
In the descriptive analysis, we observed a heterogeneous overall reduction of MMR in the region between 1990 and 2019 and heterogeneous overall increases in the GHE, GHE/GDP, and HRH availability. The correlation analysis showed a close, negative, and dependent association of the economic development level between the MMR and GHE per capita, the percentage of GHE to GDP, the availability of HRH, and the coverage of SBA. We observed the lowest MMRs when GHE as a percentage of GDP was close to 3% or about US$400 GHE per capita, HRH availability of 6 doctors, nurses, and midwives per 1,000 inhabitants, and skilled birth attendance levels above 90%.

Conclusions
Within the framework of the Sustainable Development Goals (SDGs) agenda, health policies aimed at the effective reduction of maternal mortality should consider allocating more resources as a necessary but not sufficient condition to achieve the goals and should prioritize the implementation of new forms of care with a gender and rights approach, as well as strengthening actions focused on vulnerable groups.
Left knee septic monoarthritis in a pediatric patient due to shewanella putrefaciens: case report and literature review
Authors: Madrid Nathalie Yepes , Mejia Luis Fernando , Urrego José Fernando Gomez 
Published: May 2024

Abstract
Background
Shewanella putrefaciens is a gram-negative, nonfermenting, oxidase-positive, hydrogen sulfide-producing bacillus and a halophilic bacterium, known for causing unusual infections in humans and often regarded as an opportunistic pathogen. Its diverse symptoms have a significant impact on human health, with 260 documented disorders reported in the literature over the last 40 years, highlighting its potential danger.

Case presentation
We present the case of a previously healthy 15-year-old male patient who sustained a self-inflicted sharp-object injury while working in the field, resulting in secondary septic monoarthritis due to Shewanella putrefaciens.

Conclusions
This case highlights the bacteriological and clinical characteristics, as well as the antibiogram, of Shewanella spp. Given the recent increase in notifications of Shewanella infections, predominantly by S. algae and S. putrefaciens, it is essential to consider these pathogens in patients with a history of contact with bodies of water. Special attention must be paid to their resistance patterns in patient management to prevent the development of intrinsic antimicrobial resistance.
The landscape of transcriptional profiles in human oocytes with different chromatin configurations
Authors: Zhang Yi-Ran , Yin Ying , Guo Shi-Meng , Wang Yu-Fan , Zhao Guang-Nian , Ji Dong-Mei , Zhou Li-Quan 
Published: May 2024

AbstractWith increasingly used assisted reproductive technology (ART), the acquisition of high-quality oocytes and early embryos has become the focus of much attention. Studies in mice have found that the transition of chromatin conformation from non-surrounded nucleolus (NSN) to surrounded nucleolus (SN) is essential for oocyte maturation and early embryo development, and similar chromatin transition also exists in human oocytes. In this study, we collected human NSN and SN oocytes and investigated their transcriptome. The analysis of differentially expressed genes showed that epigenetic functions, cyclin-dependent kinases and transposable elements may play important roles in chromatin transition during human oocyte maturation. Our findings provide new insights into the molecular mechanism of NSN-to-SN transition of human oocyte and obtained new clues for improvement of oocyte in vitro maturation technique.
Aftermath Türkiye’s double earthquake: detailed analysis of fracture characteristics and acute management from a level I trauma center
Authors: Gökmen Mehmet Yiğit , Uluöz Mesut , Pazarcı Özhan , Çiloğlu Osman , Varmış Hasan Orkun 
Published: May 2024

Abstract
Background
This research investigated surgical interventions for the treatment of extremity and pelvic fractures and aimed to provide an analysis of management challenges under crisis conditions in a Level I Trauma Center after Türkiye’s February 6, 2023, earthquakes.

Methods
The study was a retrospective examination of the medical records of 243 fracture cases associated with the earthquakes. The age, gender, time of admission, types of extremity and pelvic fractures, anatomical localizations, and surgical treatment methods for fractures were recorded. The results of these parameters were evaluated in detail, together with the results of other surgical treatments performed in the hospital in the first week after the disaster, such as fasciotomy, amputation, and wound debridement.

Results
Most of the 243 (119 males and 124 females) patients with extremity fractures and pelvic fractures receiving surgical treatment were adults (n = 182, 74.9%). The most common lower extremity fractures among all fracture cases were tibial shaft (30.8%) and femoral shaft (20.6%) fractures. A total of 33 patients had surgical procedures for the treatment of two or more significant bone fractures involving either the extremity or the pelvic ring. The analysis showed that the median age of patients who underwent surgery due to extremity and pelvic fractures was 36 years, with a range of 1 to 91 years, which was statistically increased compared to patients who received surgery for other musculoskeletal injuries such as fasciotomy, amputation and debridement (p < 0.001).

Conclusion
Fractures were one of the most common musculoskeletal injuries in the first days after earthquakes, and the management of fractures differs significantly from soft tissue injuries and amputation surgeries as they require implants, special instruments, and imaging devices. The delivery of healthcare is often critically impaired after a severe earthquake. Shortages of consumables such as orthopedic implants, power drills, fluoroscopy equipment, and the need for additional staff should be addressed immediately after the earthquake, ideally by the end of the first day.
Machine learning derived serum creatinine trajectories in acute kidney injury in critically ill patients with sepsis
Authors: Takkavatakarn Kullaya , Oh Wonsuk , Chan Lili , Hofer Ira , Shawwa Khaled , Kraft Monica , Shah Neomi , Kohli-Seth Roopa , Nadkarni Girish N. , Sakhuja Ankit 
Published: May 2024

Abstract
Background
Current classification for acute kidney injury (AKI) in critically ill patients with sepsis relies only on its severity-measured by maximum creatinine which overlooks inherent complexities and longitudinal evaluation of this heterogenous syndrome. The role of classification of AKI based on early creatinine trajectories is unclear.

Methods
This retrospective study identified patients with Sepsis-3 who developed AKI within 48-h of intensive care unit admission using Medical Information Mart for Intensive Care-IV database. We used latent class mixed modelling to identify early creatinine trajectory-based classes of AKI in critically ill patients with sepsis. Our primary outcome was development of acute kidney disease (AKD). Secondary outcomes were composite of AKD or all-cause in-hospital mortality by day 7, and AKD or all-cause in-hospital mortality by hospital discharge. We used multivariable regression to assess impact of creatinine trajectory-based classification on outcomes, and eICU database for external validation.

Results
Among 4197 patients with AKI in critically ill patients with sepsis, we identified eight creatinine trajectory-based classes with distinct characteristics. Compared to the class with transient AKI, the class that showed severe AKI with mild improvement but persistence had highest adjusted risks for developing AKD (OR 5.16; 95% CI 2.87–9.24) and composite 7-day outcome (HR 4.51; 95% CI 2.69–7.56). The class that demonstrated late mild AKI with persistence and worsening had highest risks for developing composite hospital discharge outcome (HR 2.04; 95% CI 1.41–2.94). These associations were similar on external validation.

Conclusions
These 8 classes of AKI in critically ill patients with sepsis, stratified by early creatinine trajectories, were good predictors for key outcomes in patients with AKI in critically ill patients with sepsis independent of their AKI staging.
Insertion of short L1 sequences generates inter-strain histone acetylation differences in the mouse
Authors: Boyboy Beverly Ann G. , Ichiyanagi Kenji 
Published: May 2024

Abstract
Background
Gene expression divergence between populations and between individuals can emerge from genetic variations within the genes and/or in the cis regulatory elements. Since epigenetic modifications regulate gene expression, it is conceivable that epigenetic variations in cis regulatory elements can also be a source of gene expression divergence.

Results
In this study, we compared histone acetylation (namely, H3K9ac) profiles in two mouse strains of different subspecies origin, C57BL/6 J (B6) and MSM/Ms (MSM), as well as their F1 hybrids. This identified 319 regions of strain-specific acetylation, about half of which were observed between the alleles of F1 hybrids. While the allele-specific presence of the interferon regulatory factor 3 (IRF3) binding sequence was associated with allele-specific histone acetylation, we also revealed that B6-specific insertions of a short 3′ fragment of LINE-1 (L1) retrotransposon occur within or proximal to MSM-specific acetylated regions. Furthermore, even in hyperacetylated domains, flanking regions of non-polymorphic 3′ L1 fragments were hypoacetylated, suggesting a general activity of the 3′ L1 fragment to induce hypoacetylation. Indeed, we confirmed the binding of the 3′ region of L1 by three Krüppel-associated box domain-containing zinc finger proteins (KZFPs), which interact with histone deacetylases. These results suggest that even a short insertion of L1 would be excluded from gene- and acetylation-rich regions by natural selection. Finally, mRNA-seq analysis for F1 hybrids was carried out, which disclosed a link between allele-specific promoter/enhancer acetylation and gene expression.

Conclusions
This study disclosed a number of genetic changes that have changed the histone acetylation levels during the evolution of mouse subspecies, a part of which is associated with gene expression changes. Insertions of even a very short L1 fragment can decrease the acetylation level in their neighboring regions and thereby have been counter-selected in gene-rich regions, which may explain a long-standing mystery of discrete genomic distribution of LINEs and SINEs.
Hyper-physiologic mechanical cues, as an osteoarthritis disease-relevant environmental perturbation, cause a critical shift in set points of methylation at transcriptionally active CpG sites in neo-cartilage organoids
Authors: Bloks Niek G. C. , Dicks Amanda , Harissa Zainab , Nelissen Rob G. H. H. , Hajmousa Ghazaleh , Ramos Yolande F. M. , de Almeida Rodrigo Coutinho , Guilak Farshid , Meulenbelt Ingrid 
Published: May 2024

Abstract
Background
Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stiffness, pain, and a significant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (Guilak in Best Pract Res Clin Rheumatol 25:815–823, 2011). It has been shown that post-mitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative impact on cellular performance. We hypothesize that hyper-physiologic mechanical loading leads to the accumulation of altered epigenetic markers in articular chondrocytes, resulting in a loss of the tightly regulated balance of gene expression that leads to a dysregulated state characteristic of the OA disease state.

Results
We showed that hyper-physiological loading evokes consistent changes in CpGs associated with expression changes (ML-tCpGs) in ITGA5, CAV1, and CD44, among other genes, which together act in pathways such as anatomical structure morphogenesis (GO:0009653) and response to wound healing (GO:0042060). Moreover, by comparing the ML-tCpGs and their associated pathways to tCpGs in OA pathophysiology (OA-tCpGs), we observed a modest but particular interconnected overlap with notable genes such as CD44 and ITGA5. These genes could indeed represent lasting detrimental changes to the phenotypic state of chondrocytes due to mechanical perturbations that occurred earlier in life. The latter is further suggested by the association between methylation levels of ML-tCpGs mapped to CD44 and OA severity.

Conclusion
Our findings confirm that hyper-physiological mechanical cues evoke changes to the methylome-wide landscape of chondrocytes, concomitant with detrimental changes in positional gene expression levels (ML-tCpGs). Since CAV1, ITGA5, and CD44 are subject to such changes and are central and overlapping with OA-tCpGs of primary chondrocytes, we propose that accumulation of hyper-physiological mechanical cues can evoke long-lasting, detrimental changes in set points of gene expression that influence the phenotypic healthy state of chondrocytes. Future studies are necessary to confirm this hypothesis.