bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALPL regulates pro-angiogenic capacity of mesenchymal stem cells through ATP-P2X7 axis controlled exosomes secretion
Authors: Dong Jiayi , Zhao Wanmin , Zhao Jiangdong , Chen Ji , Liu Ping , Zheng Xueni , Li Dehua , Xue Yang , Zhou Hongzhi 
Published: April 2024

Abstract
Background
Early-onset bone dysplasia is a common manifestation of hypophosphatasia (HPP), an autosomal inherited disease caused by ALPL mutation. ALPL ablation induces prototypical premature bone ageing characteristics, resulting in impaired osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMMSCs). As angiogenesis is tightly coupled with osteogenesis, it also plays a necessary role in sustaining bone homeostasis. We have previously observed a decrease in expression of angiogenesis marker gene CD31 in the metaphysis of long bone in Alpl+/− mice. However, the role of ALPL in regulation of angiogenesis in bone has remained largely unknown.

Methods
Exosomes derived from Normal and HPP hBMMSCs were isolated and identified by ultracentrifugation, transmission electron microscopy, and nanoparticle size measurement. The effects of ALPL on the angiogenic capacity of hBMMSCs from HPP patients were assessed by immunofluorescence, tube formation, wound healing and migration assay. exo-ELISA and Western Blot were used to evaluate the exosomes secretion of hBMMSCs from HPP, and the protein expression of VEGF, PDGFBB, Angiostatin and Endostatin in exosomes respectively.

Results
We verified that ALPL ablation resulted in impaired pro-angiogenic capacity of hBMMSCs, accounting for reduced migration and tube formation of human umbilical vein endothelial cells, as the quantities and proteins composition of exosomes varied with ALPL expression. Mechanistically, loss of function of ALPL enhanced ATP release. Additional ATP, in turn, led to markedly elevated level of ATP receptor P2X7, which consequently promoted exosomes secretion, resulting in a decreased capacity to promote angiogenesis. Conversely, inhibition of P2X7 increased the angiogenic induction capacity by preventing excessive release of anti-angiogenic exosomes in ALPL deficient-hBMMSCs.

Conclusion
The ALPL–ATP axis regulates the pro-angiogenic ability of hBMMSCs by controlling exosomes secretion through the P2X7 receptor. Thus, P2X7 may be proved as an effective therapeutic target for accelerating neovascularization in ALPL–deficient bone defects.
Bacteria-driven nanosonosensitizer delivery system for enhanced breast cancer treatment through sonodynamic therapy-induced immunogenic cell death
Authors: Du Meng , Wang Ting , Peng Wangrui , Feng Renjie , Goh MeeiChyn , Chen Zhiyi 
Published: April 2024

Abstract
Background
Sonodynamic therapy (SDT) has shown promise as a non-invasive cancer treatment due to its local effects and excellent tissue penetration. However, the limited accumulation of sonosensitizers at the tumor site hinders its therapeutic efficacy. Although nanosonosensitizers have improved local tumor accumulation through passive targeting via the enhanced permeability and retention effect (EPR), achieving sufficient accumulation and penetration into tumors remains challenging due to tumor heterogeneity and inaccurate targeting. Bacteria have become a promising biological carrier due to their unique characteristic of active targeting and deeper penetration into the tumor.

Methods
In this study, we developed nanosonosensitizers consisting of sonosensitizer, hematoporphyrin monomethyl ether (HMME), and perfluoro-n-pentane (PFP) loaded poly (lactic-co-glycolic) acid (PLGA) nanodroplets (HPNDs). These HPNDs were covalently conjugated onto the surface of Escherichia coli Nissle 1917 (EcN) using carbodiimine chemistry. EcN acted as an active targeting micromotor for efficient transportation of the nanosonosensitizers to the tumor site in triple-negative breast cancer (TNBC) treatment. Under ultrasound cavitation, the HPNDs were disrupted, releasing HMME and facilitating its uptakes by cancer cells. This process induced reactive oxygen species (ROS)-mediated cell apoptosis and immunogenic cell death (ICD) in vitro and in vivo.

Results
Our bacteria-driven nanosonosensitizer delivery system (HPNDs@EcN) achieved superior tumor localization of HMME in vivo compared to the group treated with only nanosonosensitizers. This enhanced local accumulation further improved the therapeutic effect of SDT induced-ICD therapeutic effect and inhibited tumor metastasis under ultrasound stimulation.

Conclusions
Our research demonstrates the potential of this ultrasound-responsive bacteria-driven nanosonosensitizer delivery system for SDT in TNBC. The combination of targeted delivery using bacteria and nanosonosensitizer-based therapy holds promise for achieving improved treatment outcomes by enhancing local tumor accumulation and stimulating ICD.

Graphical Abstract
Successful ECMO treatment in patients with cerebral hemorrhage and PROC gene mutation associated with VTE: a case report
Authors: Wang Lijie , Ma Chengyong , Wang Luping , Ding Qianrong , Yang Hao , Wang Bo , Wu Qin 
Published: April 2024

AbstractIn this report, we report a case of a middle-aged male, admitted to the ICU with cerebral hemorrhage resulting from a severe high-altitude fall. The patient encountered significant challenges in oxygenation index correction, attributed to extensive embolism in both the primary and branch pulmonary arteries. Consequently, the patient underwent an immediate initiation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy, persisting for 20 days. During this treatment period, a mutation in the protein C (PROC) gene was identified. The medical team meticulously navigated the delicate balance between anticoagulation and bleeding risks. Eventually, the patient was successfully weaned off VA-ECMO and subsequently discharged. This report aims to delve into the etiology and therapeutic approaches of this uncommon case, with the intention of offering insightful reference for managing similar clinical scenarios in the future.
RUNX1-BMP2 promotes vasculogenic mimicry in laryngeal squamous cell carcinoma via activation of the PI3K-AKT signaling pathway
Authors: Zhu Qingwen , Zhang Xinyu , Lu Fei , Miao Siyu , Zhang Chunyang , Liu Zhenzhen , Gao Zejun , Qi Meihao , An Xiaogang , Geng Panling , Wang Sufang , Ren Hongbo , Han Fugen , Zhang Ruyue , Zha DingJun 
Published: April 2024

Abstract
Background
Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck. Vasculogenic mimicry (VM) is crucial for tumor growth and metastasis and refers to the formation of fluid channels by invasive tumor cells rather than endothelial cells. However, the regulatory mechanisms underlying VM during the malignant progression of LSCC remain largely unknown.

Methods
Gene expression and clinical data for LSCC were obtained from the TCGA and Gene GEO (GSE27020) databases. A risk prediction model associated with VM was established using LASSO and Cox regression analyses. Based on their risk scores, patients with LSCC were categorized into high- and low-risk groups. The disparities in immune infiltration, tumor mutational burden (TMB), and functional enrichment between these two groups were examined. The core genes in LSCC were identified using the machine learning (SVM-RFE) and WGCNA algorithms. Subsequently, the involvement of bone morphogenetic protein 2 (BMP2) in VM and metastasis was investigated both in vitro and in vivo. To elucidate the downstream signaling pathways regulated by BMP2, western blotting was performed. Additionally, ChIP experiments were employed to identify the key transcription factors responsible for modulating the expression of BMP2.

Results
We established a new precise prognostic model for LSCC related to VM based on three genes: BMP2, EPO, and AGPS. The ROC curves from both TCGA and GSE27020 validation cohorts demonstrated precision survival prediction capabilities, with the nomogram showing some net clinical benefit. Multiple algorithm analyses indicated BMP2 as a potential core gene. Further experiments suggested that BMP2 promotes VM and metastasis in LSCC. The malignant progression of LSCC is promoted by BMP2 via the activation of the PI3K-AKT signaling pathway, with the high expression of BMP2 in LSCC resulting from its transcriptional activation by runt-related transcription factor 1 (RUNX1).

Conclusion
BMP2 predicts poor prognosis in LSCC, promotes LSCC VM and metastasis through the PI3K-AKT signaling pathway, and is transcriptionally regulated by RUNX1. BMP2 may be a novel, precise, diagnostic, and therapeutic biomarker of LSCC.
Exploring indicators of natural recovery from alcohol and drug use problems: findings from the life in recovery survey in Flanders
Authors: De Meyer Florian , Zerrouk Amine , De Ruysscher Clara , Vanderplasschen Wouter 
Published: April 2024

Abstract
Introduction
Research has established natural recovery (NR) as an important pathway to substance use recovery. Studies investigating correlates of NR have mainly focused on demographic and substance use variables rather than life circumstances. This study seeks to better understand the phenomenon of natural recovery by (i) validating the international scientific literature concerning demographic and substance use indicators of NR in Flanders and (ii) assessing the additional explanatory power of recovery strengths and barriers during active addiction, controlling for demographic and substance use covariates.

Methods
A total of 343 persons in recovery from alcohol or drug use problems (≥ 3 months) completed an online cross-sectional survey in Flanders. Participants in NR and in recovery after following treatment were compared using multivariate linear regression models. Reasons for not following treatment were analyzed using inductive thematic analysis.

Results
Higher education level, lower severity of dependence, and cannabis use as the main problem substance (vs. alcohol) were statistically significant (p < 0.05) correlates of NR. When scores for the number of barriers and strengths associated with active addiction were added, barriers (but not strengths) were significantly associated with NR. When barrier items were individually tested, having untreated emotional or mental health problems, having a driver’s license revoked and damaging property were statistically significant correlates. The most reported reason for not entering treatment was not experiencing any need to do so.

Conclusion
The results highlight the importance of a holistic approach to recovery support across multiple life domains. Limitations and opportunities for further research are discussed.
A novel model of locking plate and locking spongious screw: a biomechanical in vitro comparison study with classical locking plate
Authors: Parmaksizoglu Fatih , Kilic Sinan , Cetin Onur 
Published: April 2024

Abstract
Background
Locking plates are commonly used for the fixation of comminuted, periprosthetic and osteoporotic bone fractures. These plates are secured to the bone with screws, creating a stable connection with fixed angle between the plate and the screws. In this biomechanical in vitro study, our aim is to evaluate and compare the novel locking plate-locking spongious screw model with FDA approved classical locking plate.

Methods
Sawbone PCF-15 osteoporotic bone model was utilized to simulate osteoporotic bone conditions. Two screws were used to attach both the classical locking plate and the novel locking plate-locking spongious screw model to these bone models. The attachment strength of the screws to the bone blocks was measured by pull-out tests.

Results
Novel locking plate-locking spongious screw model exhibited an 84.38% stronger attachment to the osteoporotic bone model compared to the current locking plate model.

Conclusions
In conclusion, one of the important problems in the locking plates which is the high Pull-out risk of the locking spongious screws can been resolved with our proposed new model and has a chance of having a better purchase especially in osteoporotic bones.
Genetic analysis of 37 cases with primary periodic paralysis in Chinese patients
Authors: Zhao Xuechao , Ning Haofeng , Liu Lina , Zhu Chaofeng , Zhang Yinghui , Sun Guifang , Ren Huanan , Kong Xiangdong 
Published: April 2024

Abstract
Background
Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population.

Results
We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants.

Conclusions
Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.
Supported exercise TrAining for Men wIth prostate caNcer on Androgen deprivation therapy (STAMINA): study protocol for a randomised controlled trial of the clinical and cost-effectiveness of the STAMINA lifestyle intervention compared with optimised usual care, including internal pilot and parallel process evaluation
Authors: McNaught Emma , Reale Sophie , Bourke Liam , Brown Janet E. , Collinson Michelle , Day Florence , Hewison Jenny , Farrin Amanda J. , Ibeggazene Saïd , Innes Aidan Q. , Mason Ellen , Meads David , Scope Alison , Taylor Chris , Taylor Steph JC. , Turner Rebecca R. , Rosario Derek J. ,   on behalf of the STAMINA co-investigators
Published: April 2024

Abstract
Background
UK national clinical guidance recommends that men with prostate cancer on androgen deprivation therapy are offered twice weekly supervised aerobic and resistance exercise to address iatrogenic harm caused by treatment. Very few NHS trusts have established adequate provision of such services. Furthermore, interventions fail to demonstrate sustained behaviour change. The STAMINA lifestyle intervention offers a system-level change to clinical care delivery addressing barriers to long-term behaviour change and implementation of new prostate cancer care pathways. This trial aims to establish whether STAMINA is clinically and cost-effective in improving cancer-specific quality of life and/or reducing fatigue compared to optimised usual care. The process evaluation aims to inform the interpretation of results and, if the intervention is shown to benefit patients, to inform the implementation of the intervention into the NHS.

Methods
Men with prostate cancer on androgen deprivation therapy (n = 697) will be identified from a minimum of 12 UK NHS trusts to participate in a multi-centre, two-arm, individually randomised controlled trial. Consenting men will have a ‘safety to exercise’ check and be randomly allocated (5:4) to the STAMINA lifestyle intervention (n = 384) or optimised usual care (n = 313). Outcomes will be collected at baseline, 3-, 6- and 12-month post-randomisation. The two primary outcomes are cancer-specific quality of life and fatigue. The parallel process evaluation will follow a mixed-methods approach to explore recruitment and aspects of the intervention including, reach, fidelity, acceptability, and implementation. An economic evaluation will estimate the cost-effectiveness of the STAMINA lifestyle intervention versus optimised usual care and a discrete choice experiment will explore patient preferences.

Discussion
The STAMINA lifestyle intervention has the potential to improve quality of life and reduce fatigue in men on androgen deprivation therapy for prostate cancer. Embedding supervised exercise into prostate cancer care may also support long-term positive behaviour change and reduce adverse events caused by treatment. Findings will inform future clinical care and could provide a blueprint for the integration of supervised exercise and behavioural support into other cancer and/or clinical services.

Trial registration
ISRCTN 46385239, registered on 30/07/2020. Cancer Research UK 17002, retrospectively registered on 24/08/2022.
Remote or in-clinic? The effect of service delivery mode on hearing aid output: study protocol for a double-blinded, randomised trial in adults with mild to moderate sensorineural hearing loss
Authors: Lett Craig , Welch David , Dobson Rosie 
Published: April 2024

Abstract
Background
Teleaudiology can potentially improve access to hearing healthcare services. Remote hearing aid fittings offer a new mode of service delivery that removes barriers of geography and access to an audiologist. Real-ear measurements (REMs) are the gold standard for hearing aid output verification but require in-clinic appointments. This study will investigate whether remote hearing aid fittings can provide clinically equivalent outcomes when compared to current, in-clinic, best practice guidelines.

Research design
A repeated measure, double-blinded crossover design will be used. Participants will be randomly allocated to one of two groups to determine order of intervention, balanced for degree of hearing loss.

Study sample
Sixty adults with mild to moderate hearing loss and at least 1 year of experience with hearing aids will be recruited.

Data collection and analysis
Participants will complete two hearing aid fitting protocols, one using an in-clinic fitting process and the other using a remote (at-home) fitting process. In-clinic fittings will include REMs with adjustments to standard (NAL-NL2) prescription targets. The two fitting protocols will then be randomly assigned to participants in a crossover design, so participants and researchers will be blinded to the order of the two fitting protocols. Participants will then have a 4-week period with follow-up appointments for participant-directed gain adjustment. For each fitting protocol, participants will complete objective measurements of final hearing aid output with REMs, speech-in-noise testing, subjective measurements of hearing aid performance, and quality of life measurements. They will then begin an identical period of living with, adjusting, and objective assessment with the other fitting protocol. Data will be analysed as repeated measures with statistical control for potential confounding variables.

Results
Data will compare the four-frequency average real-ear aided response (4FREAR) for hearing aids programmed in-clinic and hearing aids programmed remotely, after participant-directed gain adjustments. Secondary measures will assess clinically significant differences in estimated speech intelligibility, hearing-related quality of life, hearing aid benefit, sound quality and preference, and speech-in-noise ability.

Conclusions
This study will inform the development of best practice guidelines for remote hearing aid fittings. If no clinically significant differences are found between in-clinic and remote fit hearing aids, it has the potential to expand teleaudiology initiatives.

Trial registration
Australian New Zealand Clinical Trial Registry, ACTRN12623000028606p. Date of registration: 12 January 2023.
Preparation and characterization of liquefied eggplant branch bio-based controlled-release fertilizer
Authors: Guo Yanle , Zhuang Fengyuan , Cui Qunxiang , Zhang Shugang , Hao Zhenping , Shi Yiyun , Lu Hao , Shi Xiaoqing 
Published: April 2024

AbstractBio-based coating materials have received increased attention because of their low-cost, environmentally friendly, and sustainable properties. In this paper, a novel coating material was developed to coat ureas using bio-based coating material derived from liquefied eggplant branches to form controlled-release ureas (CRUs). Also, the optimum proportion of liquefier was studied. Furthermore, dimethyl siloxane was used to modify liquified eggplant branches to make them hydrophobic, resulting in hydrophobic controlled-release ureas (SCRUs). This hydrophobic-enabled coating is environmentally friendly and highly efficient. The products were characterized by specific scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry, and the water contact angles of CRUs and SCRUs were determined. The nutrient-release characteristics of the SCRUs in water were determined at 25 °C and compared with those of CRUs. The results showed that the modification with dimethyl siloxane reduced the N release rate and increased the longevity of the fertilizer coated with hydrophobic bio-based coating material. In addition, organosilicon atoms on the SCRU surface also block the micro-holes on the coating and thus reduce the entry of water onto the coating. The results suggest that the new coating technology can create a hydrophobic surface on bio-based coating material and thus improve their controlled-release characteristics.
Sharp coefficient inequalities of starlike functions connected with secant hyperbolic function
Authors: Raza Mohsan , Bano Khadija , Xin Qin , Tchier Fairouz , Malik Sarfraz Nawaz 
Published: April 2024

AbstractThis article comprises the study of class $\mathcal{S}_{E}^{\ast }$

S
E
∗

that represents the class of normalized analytic functions satisfying ${\varsigma \mathsf{f}}^{\prime }(z)/\mathsf{f}( {\varsigma })\prec \sec h ( \varsigma ) $
ς

f
′

(
z
)
/
f
(
ς
)
≺
sec
h
(
ς
)
. The geometry of functions of class $\mathcal{S}_{E}^{\ast }$

S
E
∗

is star-shaped, which is confined in the symmetric domain of a secant hyperbolic function. We find sharp coefficient results and sharp Hankel determinants of order two and three for functions in the class $\mathcal{S}_{E}^{\ast }$

S
E
∗

. We also investigate the same sharp results for inverse coefficients.