bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global, regional, and national burdens of facial fractures: a systematic analysis of the global burden of Disease 2019
Authors: Zhang Ze-Xing , Xie Long , Li Zhi 
Published: February 2024

Abstract
Background
The incidence of facial fractures has undergone tremendous changes in recent years as a result of socio-economic development and aging populations. Currently, there is a lack of updated and comprehensive analyses of global trends and causes of facial fractures. The Global Burden of Disease (GBD) database is a product of a global research organization used to quantify the global impact of hundreds of diseases, injuries, and risk factors. The aim of this study was to update global burden of facial fractures from 1990 to 2019 by using the GBD2019.

Materials and methods
The present study extracted the global incidence, prevalence, and years lived with disability (YLDs) for facial fractures, as well as the age-standardized rates (ASRs) of these variables using the Global Burden of Disease (GBD) 2019 database. The estimated annual percentage change (EAPC) was used to assess the trends of ASRs.

Results
Between 1990 and 2019, the incidence of facial fractures increased from 8,943,707 to 10,676,340, but the age-standardized incidence rate (ASIR) decreased from 161.5 to 138.8 per 100,000. Prevalence and YLDs exhibited the same trend as incidence. Over the 30 years, the incidence of facial fractures was consistently greater in males than in females. However, females aged ˃ 75 years had higher fracture incidence rates than males aged ˃ 75 years in 2019. The leading cause of facial fractures was falls, and both the age-standardized prevalence rate (ASPR) and age-standardized years lived with disability rate (ASYR) of falls increased with age.

Conclusion
Facial fractures still represent a significant burden to the world. Incidence, prevalence and YLDs all showed increasing trends, while ASRs decreased gradually from 1990 to 2019. Enhancing the quality of facial fractures data is helpful for monitoring the burden of facial fractures.
Feasibility of a physical exercise intervention for patients on a palliative care unit: a critical analysis
Authors: Schwonke Inken , Freitag Nils , Aschendorf Paula , Wucharz Kerstin , Thieme Johanna , Appelmann Iris , Schumann Moritz , Elsner Frank 
Published: February 2024

Abstract
Background
Recent exercise intervention studies have shown promising results in improving quality of life (QoL) and physical function (PF) in diverse chronic disease and advanced cancer patients. However, the effects of structured exercise in palliative care patients, having different therapeutic needs, lower life expectancies and PFs remain unknown. This study primarily aimed to assess the feasibility of an exercise intervention with follow-up by analysing recruitment numbers, screening procedures, acceptability, preferences, and safety of the exercise intervention as well as retention in follow-up. Our secondary aims related to changes in QoL and PF.

Methods
This study comprised of a one-arm design without a control group. Over 6 months, every in-hospital palliative care unit (PCU) patient was screened for eligibility. Eligible patients were asked to participate in a 2-week exercise intervention consisting of resistance training and/or endurance training with moderate or high intensity based on personal preferences and a 4-week follow-up. Before and after the exercise intervention, QoL and PF were assessed and a qualitative interview after the intervention addressed expectations and experiences of the exercise intervention. For follow-up, patients were provided with information on independent training and after 1 and 4 weeks a QoL assessment and qualitative interview were conducted.

Results
Of 124 patients screened, 10 completed the intervention with an adherence rate of (80 ± 25%), of which 6 patients completed follow-up. Endurance training was the most performed training type and only a few minor adverse events occurred in certain or likely connection to the exercise intervention. While physical QoL and PF measured by arm curl strength and time up and go performance improved, mental QoL and the other PF tests remained unchanged.

Conclusion
Despite the challenges that were faced in our screening and testing process, that are specific to the palliative patient population with their unique therapeutic requirements and varying mental-/ physical capabilities, we discovered the 2-week exercise intervention to be feasible, safe, and well tolerated by palliative care patients. Moreover, it seems that short-term improvements in QoL and PF are possible. Further full scale studies are required to confirm our findings.

Trial registration
The study was retrospectively registered on 25.01.2022 in the German Clinical Trials Register (DRKS00027861)
Nurse anaesthetists’ experiences of student nurse anaesthetist learning during clinical practice: a qualitative interview study
Authors: Hedlund Jakob , Blomberg Karin , Hjelmqvist Hans , Jaensson Maria 
Published: February 2024

Abstract
Background
The professional role of a nurse anaesthetist involves taking a pedagogical approach towards students, including supervision during clinical practice. Although supervisors are facilitators of student learning, they are offered little training in adult learning principles. The aim of this study was to describe supervisors’ experience of student nurse anaesthetist learning during clinical practice in the operating room.

Method
In this qualitative interview study, 12 semi-structured individual interviews were carried out with clinical supervising nurse anaesthetists. The data were analysed inductively using thematic analysis.

Results
The results are illustrated with one theme and five sub-themes. The clinical learning situation of student nurse anaesthetists is described as a reflection of different cultures coming together. The operating room environment is a new context to students, and students enter with different clinical background and experiences. There is tension in facilitating student learning due to demands for productivity; supervisors suggest the use of separate operating rooms with a special focus on learning in the future.

Conclusion
Clinical practice facilitates student learning and is a parallel process to routine care. Thus, it requires the cultures of higher education and healthcare organizations to co-exist. This is illustrated with the theme “Contributing to students’ future professional roles by bridging the hospital and university cultures”. In the operating room, student learning is challenged by a new context and time pressure as shown by subthemes. To overcome challenges and support student learning in the operating room from a supervisors’ perspective, interprofessional student teams are suggested as a future approach and need to be further investigated.
An integrated primary care service to reduce cardiovascular disease risk in people with severe mental illness: Primrose-A - thematic analysis of its acceptability, feasibility, and implementation
Authors: Shaw Philippa , Mifsud Annabel , Osborn David , Nahata Nitisha , Hall Cerdic , Prenelle Ian , Lamb Danielle 
Published: February 2024

Abstract
Background
Cardiovascular disease among patients with severe mental illness in England is a major preventable contributor to premature mortality. To address this, a nurse and peer-coach delivered service (Primrose-A) was implemented in three London general practices from 2019 (implementation continued during COVID-19). This study aimed to conduct interviews with patient and staff to determine the acceptability of, and experiences with, Primrose-A.

Methods
Semi-structured audio-recorded interviews with eight patients who had received Primrose-A, and 3 nurses, 1 GP, and 1 peer-coach who had delivered Primrose-A in three London-based GP surgeries were conducted. Reflexive thematic analysis was used to identify themes from the transcribed interviews.

Findings
Overall, Primrose-A was viewed positively by patients and staff, with participants describing success in improving patients’ mental health, isolation, motivation, and physical health. Therapeutic relationships between staff and patients, and long regular appointments were important facilitators of patient engagement and acceptance of the intervention. Several barriers to the implementation of Primrose-A were identified, including training, administrative and communication issues, burden of time and resources, and COVID-19.

Conclusions
Intervention acceptability could be enhanced by providing longer-term continuity of care paired with more peer-coaching sessions to build positive relationships and facilitate sustained health behaviour change. Future implementation of Primrose-A or similar interventions should consider: (1) training sufficiency (covering physical and mental health, including addiction), (2) adequate staffing to deliver the intervention, (3) facilitation of clear communication pathways between staff, and (4) supporting administrative processes.
Digitally-mediated coordination in healthcare: the effects of teleconsultation on doctor-to-doctor relational coordination
Authors: Olive Mattia Vincenzo , Gastaldi Luca , Corso Mariano 
Published: February 2024

Abstract
Background
Digitalization transforms the way in which interdependent work is coordinated, especially in healthcare settings. This work deepens the effect of teleconsultation use on health professionals’ coordination. For this aim, we rely on Relational Coordination Theory (RCT), which explores coordination as an interactive process among group participants within the context of task interdependency.

Methods
We collected data through an online survey administered to Italian specialist doctors between March and April 2023. 489 complete answers were gathered. Hypotheses have been tested through Structural Equation Modelling.

Results
We found that teleconsultation frequency of use has a positive and significant effect on both components of relational coordination, confirming our hypotheses.

Conclusions
Theoretically, this research contributes to our understanding of the effect of digitally mediated coordination mechanisms on relational coordination. In practice, we shed light on the organizational implications of telemedicine under a novel perspective, focusing on the role of professional interactions in digitally mediated work and providing useful elements for the organizational design of telemedicine.
Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study
Authors: Hou Xin-Zheng , Lv Yan-Fei , Li Yu-Shan , Wu Qian , Lv Qian-Yu , Yang Ying-Tian , Li Lan-Lan , Ye Xue-Jiao , Yang Chen-Yan , Wang Man-Shi , Cao Lin-Lin , Wang Shi-Han 
Published: February 2024

Abstract
Background
Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population.

Methods
The data came from the National Health and Nutrition Examination Survey (NHANES 2001–2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan–Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use.

Results
1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found.

Conclusion
The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.
Mucosal-associated invariant T cells in infectious diseases of respiratory system: recent advancements and applications
Authors: Lin Xue , Wang Ye , He Yanqi 
Published: February 2024

AbstractMucosal-associated invariant T (MAIT) cells are an atypical subset of T lymphocytes, which have a highly conserved semi-constant αβ chain of T-cell receptor (TCR) and recognize microbe-derived vitamin B metabolites via major histocompatibility complex class I related-1 molecule (MR1). MAIT cells get activated mainly through unique TCR-dependent and TCR-independent pathways, and express multiple functional and phenotypic traits, including innate-like functionality, T helper (Th) 1 cell immunity, Th 17 cell immunity, and tissue homing. Given the functions, MAIT cells are extensively reported to play a key role in mucosal homeostasis and infectious diseases. In the current work, we review the basic characteristics of MAIT cells and their roles in mucosal homeostasis and development of respiratory infectious diseases as well as their potential therapeutic targets.
Exosome proteomes reveal glycolysis-related enzyme enrichment in primary canine mammary gland tumor compared to metastases
Authors: Kim Hui-Su , Cho Je-Yoel 
Published: February 2024

Abstract
Objective
Numerous evidence has highlighted the differences between primary tumors and metastases. Nonetheless, the differences in exosomal proteins derived from primary tumor and metastases remain elusive. Here, we aimed to identify differentially expressed exosomal proteins from primary canine mammary gland tumor and metastases to understand how they shape their own tumor microenvironment.

Methods
We clearly distinguished primary canine mammary gland tumors (CHMp) from metastases (CHMm) and profiled the proteins within their secreted exosomes using LC–MS/MS. Moreover, the abundance of glycolysis enzymes (GPI, LDHA) in CHMp exosome was verified with Western blotting, To broaden the scope, we extended to human colorectal cancer-derived exosomes (SW480 vs. SW620) for comparison.

Results
We identified significant differences in 87 and 65 proteins derived from CHMp and CHMm, respectively. Notably, glycolysis enzymes (GPI, LDHA, LDHB, TPI1, and ALDOA) showed specific enrichment in exosomes from the primary tumor.

Conclusion
We observed significant differences in the cellular proteome between primary tumors and metastases, and intriguingly, we identified a parallel heterogeneity the protein composition of exosomes. Specifically, we reported that glycolysis enzymes were significantly enriched in CHMp exosomes compared to CHMm exosomes. We further demonstrated that this quantitative difference in glycolysis enzymes persisted across primary and metastases, extending to human colorectal cancer-derived exosomes (SW480 vs. SW620). Our findings of the specific enrichment of glycolysis enzymes in primary tumor-derived exosomes contribute to a better understanding of tumor microenvironment modulation and heterogeneity between primary tumors and metastases.
Phosphorylation of PP2Ac by PKC is a key regulatory step in the PP2A-switch-dependent AKT dephosphorylation that leads to apoptosis
Authors: Nadel Guy , Yao Zhong , Hacohen-Lev-Ran Avital , Wainstein Ehud , Maik-Rachline Galia , Ziv Tamar , Naor Zvi , Admon Arie , Seger Rony 
Published: February 2024

Abstract
Background
Although GqPCR activation often leads to cell survival by activating the PI3K/AKT pathway, it was previously shown that in several cell types AKT activity is reduced and leads to JNK activation and apoptosis. The mechanism of AKT inactivation in these cells involves an IGBP1-coupled PP2Ac switch that induces the dephosphorylation and inactivation of both PI3K and AKT. However, the machinery involved in the initiation of PP2A switch is not known.

Methods
We used phospho-mass spectrometry to identify the phosphorylation site of PP2Ac, and raised specific antibodies to follow the regulation of this phosphorylation. Other phosphorylations were monitored by commercial antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by a TUNEL assay as well as PARP1 cleavage using SDS-PAGE and Western blotting.

Results
We identified Ser24 as a phosphorylation site in PP2Ac. The phosphorylation is mediated mainly by classical PKCs (PKCα and PKCβ) but not by novel PKCs (PKCδ and PKCε). By replacing the phosphorylated residue with either unphosphorylatable or phosphomimetic residues (S24A and S24E), we found that this phosphorylation event is necessary and sufficient to mediate the PP2A switch, which ultimately induces AKT inactivation, and a robust JNK-dependent apoptosis.

Conclusion
Our results show that the PP2A switch is induced by PKC-mediated phosphorylation of Ser24-PP2Ac and that this phosphorylation leads to apoptosis upon GqPCR induction of various cells. We propose that this mechanism may provide an unexpected way to treat some cancer types or problems in the endocrine machinery.
Elevated SLC7A2 expression is associated with an abnormal neuroinflammatory response and nitrosative stress in Huntington’s disease
Authors: Gaudet Ian D. , Xu Hongyuan , Gordon Emily , Cannestro Gianna A. , Lu Michael L. , Wei Jianning 
Published: February 2024

AbstractWe previously identified solute carrier family 7 member 2 (SLC7A2) as one of the top upregulated genes when normal Huntingtin was deleted. SLC7A2 has a high affinity for l-arginine. Arginine is implicated in inflammatory responses, and SLC7A2 is an important regulator of innate and adaptive immunity in macrophages. Although neuroinflammation is clearly demonstrated in animal models and patients with Huntington’s disease (HD), the question of whether neuroinflammation actively participates in HD pathogenesis is a topic of ongoing research and debate. Here, we studied the role of SLC7A2 in mediating the neuroinflammatory stress response in HD cells. RNA sequencing (RNA-seq), quantitative RT-PCR and data mining of publicly available RNA-seq datasets of human patients were performed to assess the levels of SLC7A2 mRNA in different HD cellular models and patients. Biochemical studies were then conducted on cell lines and primary mouse astrocytes to investigate arginine metabolism and nitrosative stress in response to neuroinflammation. The CRISPR–Cas9 system was used to knock out SLC7A2 in STHdhQ7 and Q111 cells to investigate its role in mediating the neuroinflammatory response. Live-cell imaging was used to measure mitochondrial dynamics. Finally, exploratory studies were performed using the Enroll-HD periodic human patient dataset to analyze the effect of arginine supplements on HD progression. We found that SLC7A2 is selectively upregulated in HD cellular models and patients. HD cells exhibit an overactive response to neuroinflammatory challenges, as demonstrated by abnormally high iNOS induction and NO production, leading to increased protein nitrosylation. Depleting extracellular Arg or knocking out SLC7A2 blocked iNOS induction and NO production in STHdhQ111 cells. We further examined the functional impact of protein nitrosylation on a well-documented protein target, DRP-1, and found that more mitochondria were fragmented in challenged STHdhQ111 cells. Last, analysis of Enroll-HD datasets suggested that HD patients taking arginine supplements progressed more rapidly than others. Our data suggest a novel pathway that links arginine uptake to nitrosative stress via upregulation of SLC7A2 in the pathogenesis and progression of HD. This further implies that arginine supplements may potentially pose a greater risk to HD patients.
IL-6 from cerebrospinal fluid causes widespread pain via STAT3-mediated astrocytosis in chronic constriction injury of the infraorbital nerve
Authors: Yu Ning , Cui Huan , Jin Sixuan , Liu Penghao , Fang Yehong , Sun Fengrun , Cao Yan , Yuan Bo , Xie Yikuan , Duan Wanru , Ma Chao 
Published: February 2024

Abstract
Background
The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure.

Methods
A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION’s CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain.

Results
CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION’s CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION’s CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION.

Conclusion
IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions.

Graphical abstract