bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefit of prompt initiation of single-inhaler fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) in patients with COPD in England following an exacerbation: a retrospective cohort study
Authors: Ismaila Afisi S. , Rothnie Kieran J. , Wood Robert P. , Banks Victoria L. , Camidge Lucinda J. , Czira Alexandrosz , Compton Chris , Sharma Raj , Millard Shannon N. , Massey Olivia , Halpin David M. G. 
Published: September 2023

Abstract
Background
Triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite dual therapy. The optimal timing of triple therapy following an exacerbation of COPD is unknown. The outcomes of prompt (≤ 30 days) vs. delayed (31–180 days) initiation of single-inhaler triple therapy with fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) following an exacerbation of COPD were examined.

Methods
This was a retrospective cohort study of linked English primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Patients aged ≥ 35 years with COPD were indexed on the first and/or earliest date of exacerbation between November 15, 2017 and March 31, 2019 with subsequent FF/UMEC/VI initiation within 180 days. Patients were required to be continuously registered with a general practitioner for ≥ 12 months prior to and following index. Subsequent exacerbations, direct medical costs, and hospital readmissions were compared between prompt and delayed initiators. Inverse probability of treatment weighting was used to adjust for measured confounders between cohorts.

Results
Overall, 1599 patients were included (prompt: 393, delayed: 1206). After weighting, prompt initiators had numerically lower moderate/severe exacerbations compared with delayed initiators (rate ratio: 0.87, 95% confidence interval [CI]: 0.76–1.01, p = 0.0587). Both all-cause and COPD-related 30-day hospital readmissions were significantly lower among patients with prompt initiation compared with delayed initiators (all-cause: 23.6% vs. 34.6%, odds ratio [95% CI]: 0.58 [0.36–0.95], p = 0.0293; COPD-related: 20.3% vs. 30.6%, odds ratio [95% CI]: 0.58 [0.35–0.96], p = 0.0347). Prompt initiators also had numerically lower all-cause total costs and significantly lower COPD-related costs per-person-per year compared with delayed initiators (COPD-related: £742 vs. £801, p = 0.0016).

Conclusion
Prompt initiation of FF/UMEC/VI following a moderate/severe exacerbation was associated with fewer subsequent exacerbations, fewer hospital readmissions, and lower COPD-related medical costs compared with delayed initiation.
Measuring efficiency of public hospitals under the impact of Covid-19: the case of Türkiye
Authors: Sülkü Seher Nur , Mortaş Alper , Küçük Aziz 
Published: September 2023

AbstractThe Covid-19 pandemic has had serious medical, administrative and financial effects on the health system and hospitals around the world. In Türkiye, compared to 2019 realizations, in 2020 and 2021 respectively there were 39% and 21% decrease in the number of outpatient services and 29% and 17% decline in total inpatient services of public hospitals. The main subject of this research is how the pandemic period affects the Turkish public hospitals’ efficiency. We have measured the technical efficiency of outpatient and inpatient care services of Turkish public hospitals using Stochastic Frontier Analysis (SFA). The dataset includes 563 hospitals for the years 2015 through 2021. Inputs of number of physicians, nurses and other medical staff, and number of beds and their interactions with each other are introduced to the SFA models of outputs of outpatient visits and inpatient discharges adjusted with case mix index are derived. Firstly, we found that the years associated with Covid-19 have a significant negative impact on the inpatient service efficiency. Training and Research and City Hospitals have low efficiency scores in outpatient services but high efficiency scores in inpatient services. In addition, the regions with high population rates have positive impact in outpatient efficiency and negative impact in inpatient efficiency. During the pandemic, city hospitals, have received large investments, gained a key role by increasing both the patient load and their efficiency. Future reforms can be guided by taking advantage of the efficiency differences of hospitals in different environmental factors.
Advances in biological functions and applications of apoptotic vesicles
Authors: Zou Xianghui , Lei Qian , Luo Xinghong , Yin Jingyao , chen Shuoling , Hao Chunbo , Shiyu Liu , Ma Dandan 
Published: September 2023

AbstractBackgroundApoptotic vesicles are extracellular vesicles generated by apoptotic cells that were previously regarded as containing waste or harmful substances but are now thought to play an important role in signal transduction and homeostasis regulation.MethodsIn the present review, we reviewed many articles published over the past decades on the subtypes and formation of apoptotic vesicles and the existing applications of these vesicles.ResultsApoptotic bodies were once regarded as vesicles released by apoptotic cells, however, apoptotic vesicles are now regarded to include apoptotic bodies, apoptotic microvesicles and apoptotic exosomes, which exhibit variation in terms of biogenesis, sizes and properties. Applications of apoptotic vesicles were first reported long ago, but such reports have been rarer than those of other extracellular vesicles. At present, apoptotic vesicles have been utilized mainly in four aspects, including in direct therapeutic applications, in their engineering as carriers, in their construction as vaccines and in their utilization in diagnosis.ConclusionBuilding on a deeper understanding of their composition and characteristics, some studies have utilized apoptotic vesicles to treat diseases in more novel ways. However, their limitations for clinical translation, such as heterogeneity, have also emerged. In general, apoptotic vesicles have great application potential, but there are still many barriers to overcome in their investigation.
LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration
Authors: Hong Jong Min , Lee Jin-Woo , Seen Dong-Seung , Jeong Jae-Yeon , Huh Won-Ki 
Published: September 2023

Abstract
Background
G protein-coupled receptor heteromerization is believed to exert dynamic regulatory impact on signal transduction. CXC chemokine receptor 4 (CXCR4) and its ligand CXCL12, both of which are overexpressed in many cancers, play a pivotal role in metastasis. Likewise, lysophosphatidic acid receptor 1 (LPA1) is implicated in cancer cell proliferation and migration. In our preliminary study, we identified LPA1 as a prospective CXCR4 interactor. In the present study, we investigated in detail the formation of the CXCR4-LPA1 heteromer and characterized the unique molecular features and function of this heteromer.

Methods
We employed bimolecular fluorescence complementation, bioluminescence resonance energy transfer, and proximity ligation assays to demonstrate heteromerization between CXCR4 and LPA1. To elucidate the distinctive molecular characteristics and functional implications of the CXCR4-LPA1 heteromer, we performed various assays, including cAMP, BRET for G protein activation, β-arrestin recruitment, ligand binding, and transwell migration assays.

Results
We observed that CXCR4 forms heteromers with LPA1 in recombinant HEK293A cells and the human breast cancer cell line MDA-MB-231. Coexpression of LPA1 with CXCR4 reduced CXCL12-mediated cAMP inhibition, ERK activation, Gαi/o activation, and β-arrestin recruitment, while CXCL12 binding to CXCR4 remained unaffected. In contrast, CXCR4 had no impact on LPA1-mediated signaling. The addition of lysophosphatidic acid (LPA) further hindered CXCL12-induced Gαi/o recruitment to CXCR4. LPA or alkyl-OMPT inhibited CXCL12-induced migration in various cancer cells that endogenously express both CXCR4 and LPA1. Conversely, CXCL12-induced calcium signaling and migration were increased in LPAR1 knockout cells, and LPA1-selective antagonists enhanced CXCL12-induced Gαi/o signaling and cell migration in the parental MDA-MB-231 cells but not in LPA1-deficient cells. Ultimately, complete inhibition of cell migration toward CXCL12 and alkyl-OMPT was only achieved in the presence of both CXCR4 and LPA1 antagonists.

Conclusions
The presence and impact of CXCR4-LPA1 heteromers on CXCL12-induced signaling and cell migration have been evidenced across various cell lines. This discovery provides crucial insights into a valuable regulatory mechanism of CXCR4 through heteromerization. Moreover, our findings propose a therapeutic potential in combined CXCR4 and LPA1 inhibitors for cancer and inflammatory diseases associated with these receptors, simultaneously raising concerns about the use of LPA1 antagonists alone for such conditions.
Natural killer cells and their exosomes in viral infections and related therapeutic approaches: where are we?
Authors: Razizadeh Mohammad Hossein , Zafarani Alireza , Taghavi-Farahabadi Mahsa , Khorramdelazad Hossein , Minaeian Sara , Mahmoudi Mohammad 
Published: September 2023

AbstractInnate immunity is the first line of the host immune system to fight against infections. Natural killer cells are the innate immunity lymphocytes responsible for fighting against virus-infected and cancerous cells. They have various mechanisms to suppress viral infections. On the other hand, viruses have evolved to utilize different ways to evade NK cell-mediated responses. Viruses can balance the response by regulating the cytokine release pattern and changing the proportion of activating and inhibitory receptors on the surface of NK cells. Exosomes are a subtype of extracellular vesicles that are involved in intercellular communication. Most cell populations can release these nano-sized vesicles, and it was shown that these vesicles produce identical outcomes to the originating cell from which they are released. In recent years, the role of NK cell-derived exosomes in various diseases including viral infections has been highlighted, drawing attention to utilizing the therapeutic potential of these nanoparticles. In this article, the role of NK cells in various viral infections and the mechanisms used by viruses to evade these important immune system cells are initially examined. Subsequently, the role of NK cell exosomes in controlling various viral infections is discussed. Finally, the current position of these cells in the treatment of viral infections and the therapeutic potential of their exosomes are reviewed.
Defective quality control autophagy in Hyperhomocysteinemia promotes ER stress and consequent neuronal apoptosis through proteotoxicity
Authors: Kaur Bhavneet , Sharma Pradeep Kumar , Chatterjee Barun , Bissa Bhawana , Nattarayan Vasugi , Ramasamy Soundhar , Bhat Ajay , Lal Megha , Samaddar Sarbani , Banerjee Sourav , Roy Soumya Sinha 
Published: September 2023

AbstractHomocysteine (Hcy), produced physiologically in all cells, is an intermediate metabolite of methionine and cysteine metabolism. Hyperhomocysteinemia (HHcy) resulting from an in-born error of metabolism that leads to accumulation of high levels of Hcy, is associated with vascular damage, neurodegeneration and cognitive decline. Using a HHcy model in neuronal cells, primary cortical neurons and transgenic zebrafish, we demonstrate diminished autophagy and Hcy-induced neurotoxicity associated with mitochondrial dysfunction, fragmentation and apoptosis. We find this mitochondrial dysfunction is due to Hcy-induced proteotoxicity leading to ER stress. We show this sustained proteotoxicity originates from the perturbation of upstream autophagic pathways through an aberrant activation of mTOR and that protetoxic stress act as a feedforward cues to aggravate a sustained ER stress that culminate to mitochondrial apoptosis in HHcy model systems. Using chemical chaperones to mitigate sustained ER stress, Hcy-induced proteotoxicity and consequent neurotoxicity were rescued. We also rescue neuronal lethality by activation of autophagy and thereby reducing proteotoxicity and ER stress. Our findings pave the way to devise new strategies for the treatment of neural and cognitive pathologies reported in HHcy, by either activation of upstream autophagy or by suppression of downstream ER stress.
Advancing polytrauma care: developing and validating machine learning models for early mortality prediction
Authors: He Wen , Fu Xianghong , Chen Song 
Published: September 2023

AbstractBackgroundRapid identification of high-risk polytrauma patients is crucial for early intervention and improved outcomes. This study aimed to develop and validate machine learning models for predicting 72 h mortality in adult polytrauma patients using readily available clinical parameters.MethodsA retrospective analysis was conducted on polytrauma patients from the Dryad database and our institution. Missing values pertinent to eligible individuals within the Dryad database were compensated for through the k-nearest neighbor algorithm, subsequently randomizing them into training and internal validation factions on a 7:3 ratio. The patients of our institution functioned as external validation cohorts. The predictive efficacy of random forest (RF), neural network, and XGBoost models was assessed through an exhaustive suite of performance indicators. The SHapley Additive exPlanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) methods were engaged to explain the supreme-performing model. Conclusively, restricted cubic spline analysis and multivariate logistic regression were employed as sensitivity analyses to verify the robustness of the findings.ResultsParameters including age, body mass index, Glasgow Coma Scale, Injury Severity Score, pH, base excess, and lactate emerged as pivotal predictors of 72 h mortality. The RF model exhibited unparalleled performance, boasting an area under the receiver operating characteristic curve (AUROC) of 0.87 (95% confidence interval [CI] 0.84–0.89), an area under the precision-recall curve (AUPRC) of 0.67 (95% CI 0.61–0.73), and an accuracy of 0.83 (95% CI 0.81–0.86) in the internal validation cohort, paralleled by an AUROC of 0.98 (95% CI 0.97–0.99), an AUPRC of 0.88 (95% CI 0.83–0.93), and an accuracy of 0.97 (95% CI 0.96–0.98) in the external validation cohort. It provided the highest net benefit in the decision curve analysis in relation to the other models. The outcomes of the sensitivity examinations were congruent with those inferred from SHAP and LIME.ConclusionsThe RF model exhibited the best performance in predicting 72 h mortality in adult polytrauma patients and has the potential to aid clinicians in identifying high-risk patients and guiding clinical decision-making.
Virtual reality—enhanced walking in people post-stroke: effect of optic flow speed and level of immersion on the gait biomechanics
Authors: De Keersmaecker Emma , Van Bladel Anke , Zaccardi Silvia , Lefeber Nina , Rodriguez-Guerrero Carlos , Kerckhofs Eric , Jansen Bart , Swinnen Eva 
Published: September 2023

Abstract
Background
Optic flow—the apparent visual motion experienced while moving—is absent during treadmill walking. With virtual reality (VR), optic flow can be controlled to mediate alterations in human walking. The aim of this study was to investigate (1) the effects of fully immersive VR and optic flow speed manipulation on gait biomechanics, simulator sickness, and enjoyment in people post-stroke and healthy people, and (2) the effects of the level of immersion on optic flow speed and sense of presence.

Methods
Sixteen people post-stroke and 16 healthy controls performed two VR-enhanced treadmill walking sessions: the semi-immersive GRAIL session and fully immersive head-mounted display (HMD) session. Both consisted of five walking trials. After two habituation trials (without and with VR), participants walked three more trials under the following conditions: matched, slow, and fast optic flow. Primary outcome measures were spatiotemporal parameters and lower limb kinematics. Secondary outcomes (simulator sickness, enjoyment, and sense of presence) were assessed with the Simulator Sickness Questionnaire, Visual Analogue Scales, and Igroup Presence Questionnaire.

Results
When walking with the immersive HMD, the stroke group walked with a significantly slower cadence (-3.69strides/min, p = 0.006), longer stride time (+ 0.10 s, p = 0.017) and stance time for the unaffected leg (+ 1.47%, p = 0.001) and reduced swing time for the unaffected leg (− 1.47%, p = 0.001). Both groups responded to the optic flow speed manipulation such that people accelerated with a slow optic flow and decelerated with a fast optic flow. Compared to the semi-immersive GRAIL session, manipulating the optic flow speed with the fully immersive HMD had a greater effect on gait biomechanics whilst also eliciting a higher sense of presence.

Conclusion
Adding fully immersive VR while walking on a self-paced treadmill led to a more cautious gait pattern in people post-stroke. However, walking with the HMD was well tolerated and enjoyable. People post-stroke altered their gait parameters when optic flow speed was manipulated and showed greater alterations with the fully-immersive HMD. Further work is needed to determine the most effective type of optic flow speed manipulation as well as which other principles need to be implemented to positively influence the gait pattern of people post-stroke.
Trial registration number: The study was pre-registered at ClinicalTrials.gov (NCT04521829).
Efficacy of OLIF combined with pedicle screw internal fixation for lumbar spinal stenosis on spinal canal changes before and after surgery
Authors: Xu Wangbing , Liu Weibing , Zhong Faming , Peng Yu , Liu Xin , Yu Liangkun 
Published: September 2023

Abstract
Purpose
The purpose of the study was to evaluate the efficacy of OLIF combined with pedicle screw internal fixation in the treatment of lumbar spinal stenosis by assessing the changes in spinal canal before and after surgery.

Methods
In this retrospective study, we included sixteen patients who underwent a combination of single-segment OLIF and pedicle screw internal fixation for the treatment of lumbar spinal stenosis at the Affiliated Hospital of Jiangxi University of Chinese Medicine between February 2018 and August 2022. The patients' pre- and post-operative data were compared. Intraoperative bleeding, duration of surgery, visual analogue score (VAS), Oswestry Disability Index (ODI), disc height (DH), cross-sectional area of vertebral canal (CSAVC), cross-sectional area of dural sac (CSADS), cross-sectional area of intervertebral foramen (CSAIF), spinal canal volume (SCV), spinal canal volume expansion rate, lumbar lordosis, and sagittal vertical axis were observed and recorded. The efficacy of OLIF combined with pedicle screw internal fixation for lumbar spinal stenosis on spinal canal changes before and after surgery was summarized.

Results
The results showed that OLIF combined with pedicle screw internal fixation effectively restored disc height and increased the cross-sectional area of the spinal canal. It also had an indirect decompression effect. The intraoperative bleeding and duration of surgery were within acceptable ranges. The VAS and ODI scores significantly improved after surgery, indicating a reduction in pain and improvement in functional disability. The CSAVC, CSADS, CSAIF, SCV, and spinal canal volume expansion rate were all increased postoperatively. Additionally, there was improvement in lumbar lordosis and sagittal vertical axis. We conducted a follow-up of all patients at 1 year after the surgery. The results revealed that the parameter values at 1 year post-surgery showed varying degrees of decrease or increase compared to the immediate postoperative values. However, these values remained statistically significant when compared to the preoperative parameter values (P < 0.05).

Conclusions
OLIF combined with pedicle screw internal fixation effectively restores disc height and increases the cross-sectional area of the vertebral canal in patients with LSS, reflecting the indirect decompression effect. Measuring parameters such as DH, CSAVC, CSADS, CSAIF, SCV, and SCV expansion rate before and after surgery provides valuable information for evaluating the efficacy and functional recovery of the lumbar spine in LSS patients treated with OLIF surgery.
Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study
Authors: Højgaard Kristoffer , Szöllősi Bianka , Henningsen Kim , Minami Natsumi , Nakanishi Nobuhiro , Kaadt Erik , Tamura Makoto , Morris Richard G.M. , Takeuchi Tomonori , Elfving Betina 
Published: September 2023

AbstractNovelty-induced memory consolidation is a well-established phenomenon that depends on the activation of a locus coeruleus-hippocampal circuit. It is associated with the expression of activity-dependent genes that may mediate initial or cellular memory consolidation. Several genes have been identified to date, however, to fully understand the mechanisms of memory consolidation, additional candidates must be identified. In this cross-species study, we used a contextual novelty-exploration paradigm to identify changes in gene expression in the dorsal hippocampus of both mice and rats. We found that changes in gene expression following contextual novelty varied between the two species, with 9 genes being upregulated in mice and 3 genes in rats. Comparison across species revealed that ArfGAP with a GTPase domain, an ankyrin repeat and PH domain 3 (Agap3) was the only gene being upregulated in both, suggesting a potentially conserved role forAgap3. AGAP3 is known to regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor trafficking in the synapse, which suggests that increased transcription ofAgap3may be involved in maintaining functional plasticity. While we identified several genes affected by contextual novelty exploration, we were unable to fully reverse these changes using SCH 23390, a dopamine D1/D5receptor antagonist. Further research on the role of AGAP3 in novelty-induced memory consolidation could lead to better understanding of this process and guide future research.