bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of pyronaridine–artesunate versus artemether–lumefantrine in the treatment of acute uncomplicated malaria in children in South-West Nigeria: an open-labelled randomized controlled trial
Authors: Falade Catherine O. , Orimadegun Adebola E. , Olusola Fiyinfoluwa I. , Michael Obaro S. , Anjorin Oluwafunmibi E. , Funwei Roland I. , Adedapo Aduragbenro D. , Olusanya Abiola L. , Orimadegun Bose E. , Mokuolu Olugbenga A. 
Published: May 2023

Abstract
Background
In Nigeria, declining responsiveness to artemether–lumefantrine (AL), the artemisinin-based combination therapy (ACT) of choice since 2005, has been reported. Pyronaridine–artesunate (PA) is a newer fixed-dose ACT recently prequalified by the WHO for the treatment of uncomplicated falciparum malaria. However, PA data from the Nigerian pediatric population is scarce. Therefore, the efficacy and safety of PA and AL using the WHO 28-day anti-malarial therapeutic efficacy study protocol in Ibadan, southwest Nigeria, were compared.

Methods
In an open-labelled, randomized, controlled clinical trial, 172 children aged 3–144 months with a history of fever and microscopically confirmed uncomplicated Plasmodium falciparum malaria were enrolled in southwest Nigeria. Enrollees were randomly assigned to receive PA or AL at standard dosages according to body weight for 3 days. Venous blood was obtained for hematology, blood chemistry, and liver function tests on days 0, 3, 7, and 28 as part of the safety evaluation.

Results
165 (95.9%) of the enrolled individuals completed the study. About half (52.3%; 90/172) of enrollees were male. Eighty-seven (50.6%) received AL, while 85 (49.4%) received PA. Day 28, adequate clinical and parasitological response for PA was 92.7% [(76/82) 95% CI 83.1, 95.9] and 71.1% [(59/83) 95% CI 60.4, 79.9] for AL (0.001). Fever and parasite clearance were similar in both groups. Two of six and eight of 24 parasite recurrences were observed among PA- and AL-treated children, respectively. PCR-corrected Day-28 cure rates for PA were 97.4% (76/78) and 88.1% (59/67) for AL (= 0.04) in the per-protocol population after new infections were censored. Hematological recovery at day 28 was significantly better among PA-treated patients (34.9% 2.8) compared to those treated with AL (33.1% 3.0) (0.002). Adverse events in both treatment arms were mild and similar to the symptoms of malaria infection. Blood chemistry and liver function tests were mostly within normal limits, with an occasional marginal rise.

Conclusion
PA and AL were well-tolerated. PA was significantly more efficacious than AL in both the PCR-uncorrected and PCR-corrected per-protocol populations during this study. The results of this study support the inclusion of PA in the anti-malarial treatment guidelines in Nigeria.

Retrospective trial registration
Clinicaltrials.gov: NCT05192265.
Does multidimensional daily information predict the onset of myopia? A 1-year prospective cohort study
Authors: Peng Wei , Wang Fei , Sun Shaoming , Sun Yining , Chen Jingcheng , Wang Mu 
Published: May 2023

Abstract
Purpose
This study aimed to develop an interpretable machine learning model to predict the onset of myopia based on individual daily information.

Method
This study was a prospective cohort study. At baseline, non-myopia children aged 6–13 years old were recruited, and individual data were collected through interviewing students and parents. One year after baseline, the incidence of myopia was evaluated based on visual acuity test and cycloplegic refraction measurement. Five algorithms, Random Forest, Support Vector Machines, Gradient Boosting Decision Tree, CatBoost and Logistic Regression were utilized to develop different models and their performance was validated by area under curve (AUC). Shapley Additive exPlanations was applied to interpret the model output on the individual and global level.

Result
Of 2221 children, 260 (11.7%) developed myopia in 1 year. In univariable analysis, 26 features were associated with the myopia incidence. Catboost algorithm had the highest AUC of 0.951 in the model validation. The top 3 features for predicting myopia were parental myopia, grade and frequency of eye fatigue. A compact model using only 10 features was validated with an AUC of 0.891.

Conclusion
The daily information contributed reliable predictors for childhood’s myopia onset. The interpretable Catboost model presented the best prediction performance. Oversampling technology greatly improved model performance. This model could be a tool in myopia preventing and intervention that can help identify children who are at risk of myopia, and provide personalized prevention strategies based on contributions of risk factors to the individual prediction result.
Advancing leadership in surgery: a realist review of interventions and strategies to promote evidence-based leadership in healthcare
Authors: Gauly Julia , Court Rachel , Currie Graeme , Seers Kate , Clarke Aileen , Metcalfe Andy , Wilson Anna , Hazell Matthew , Grove Amy Louise 
Published: May 2023

Abstract
Background
Healthcare systems invest in leadership development of surgeons, surgical trainees, and teams. However, there is no agreement on how interventions should be designed, or what components they must contain to be successful. The objective of this realist review was to generate a programme theory explaining in which context and for whom surgical leadership interventions work and why.

Methods
Five databases were systematically searched, and articles screened against inclusion considering their relevance. Context-mechanism-outcome configurations (CMOCs) and fragments of CMOCs were identified. Gaps in the CMOCs were filled through deliberation with the research team and stakeholder feedback. We identified patterns between CMOCs and causal relationships to create a programme theory.

Results
Thirty-three studies were included and 19 CMOCs were developed. Findings suggests that interventions for surgeons and surgical teams improve leadership if timely feedback is delivered on multiple occasions and by trusted and respected people. Negative feedback is best provided privately. Feedback from senior-to-junior or peer-to-peer should be delivered directly, whereas feedback from junior-to-senior is preferred when delivered anonymously. Leadership interventions were shown to be most effective for those with awareness of the importance of leadership, those with confidence in their technical surgical skills, and those with identified leadership deficits. For interventions to improve leadership in surgery, they need to be delivered in an intimate learning environment, consider implementing a speak-up culture, provide a variety of interactive learning activities, show a genuine investment in the intervention, and be customised to the needs of surgeons. Leadership of surgical teams can be best developed by enabling surgical teams to train together.

Conclusions
The programme theory provides evidence-based guidance for those who are designing, developing and implementing leadership interventions in surgery. Adopting the recommendations will help to ensure interventions are acceptable to the surgical community and successful in improving surgical leadership.

Trial registration
The review protocol is registered with PROSPERO (CRD42021230709).
Pancreatic cancer stemness: dynamic status in malignant progression
Authors: Zhao Yutong , Qin Cheng , Zhao Bangbo , Wang Yuanyang , Li Zeru , Li Tianyu , Yang Xiaoying , Wang Weibin 
Published: May 2023

AbstractPancreatic cancer (PC) is one of the most aggressive malignancies worldwide. Increasing evidence suggests that the capacity for self-renewal, proliferation, and differentiation of pancreatic cancer stem cells (PCSCs) contribute to major challenges with current PC therapies, causing metastasis and therapeutic resistance, leading to recurrence and death in patients. The concept that PCSCs are characterized by their high plasticity and self-renewal capacities is central to this review. We focused specifically on the regulation of PCSCs, such as stemness-related signaling pathways, stimuli in tumor cells and the tumor microenvironment (TME), as well as the development of innovative stemness-targeted therapies. Understanding the biological behavior of PCSCs with plasticity and the molecular mechanisms regulating PC stemness will help to identify new treatment strategies to treat this horrible disease.
ICU without borders
Authors: Ostermann Marlies , Vincent Jean-Louis 
Published: May 2023

AbstractCritical illness is a continuum, but patient care is often fragmented. Value-based critical care focuses on the overall health of the patient, not on an episode of care. The “ICU without borders” model incorporates a concept where members of the critical care team are involved in the management of patients from the onset of critical illness until recovery and beyond. In this paper, we summarise the potential benefits and challenges to patients, families, staff and the wider healthcare system and list some essential requirements, including a tight governance framework, advanced technologies, investment and trust. We also argue that “ICU without borders” should be viewed as a bi-directional model, allowing extended visiting hours, giving patients and families direct access to experienced critical care staff and offering mutual aid when needed.
Cardiovascular implications and physical activity in middle-aged and older adults with a history of COVID-19 (CV COVID): a protocol for a randomised controlled trial
Authors: Rahman Mushidur , Russell Sophie L. , Okwose Nduka C. , Hood Olivia M. A. , Harwood Amy E. , McGregor Gordon , Raleigh Stuart M. , Sandhu Hardip , Roden Laura C. , Maddock Helen , Banerjee Prithwish , Jakovljevic Djordje G. 
Published: May 2023

Abstract
Background
The clinical manifestation of COVID-19 is associated with infection and inflammation of the lungs, but there is evidence to suggest that COVID-19 may also affect the structure and function of the cardiovascular system. At present, it is not fully understood to what extent COVID-19 impacts cardiovascular function in the short- and long-term following infection. The aim of the present study is twofold: (i) to define the effect of COVID-19 on cardiovascular function (i.e. arterial stiffness, cardiac systolic and diastolic function) in otherwise healthy individuals and (ii) to evaluate the effect of a home-based physical activity intervention on cardiovascular function in people with a history of COVID-19.

Methods
This prospective, single-centre, observational study will recruit 120 COVID-19-vaccinated adult participants aged between 50 and 85 years, i.e. 80 with a history of COVID-19 and 40 healthy controls without a history of COVID-19. All participants will undergo baseline assessments including 12-lead electrocardiography, heart rate variability, arterial stiffness, rest and stress echocardiography with speckle tracking imaging, spirometry, maximal cardiopulmonary exercise testing, 7-day physical activity and sleep measures and quality of life questionnaires. Blood samples will be collected to assess the microRNA expression profiles, cardiac and inflammatory biomarkers, i.e. cardiac troponin T; N-terminal pro B-type natriuretic peptide; tumour necrosis factor alpha; interleukins 1, 6 and 10; C-reactive protein; d-dimer; and vascular endothelial growth factors. Following baseline assessments, COVID-19 participants will be randomised 1:1 into a 12-week home-based physical activity intervention aiming to increase their daily number of steps by 2000 from baseline. The primary outcome is change in left ventricular global longitudinal strain. Secondary outcomes are arterial stiffness, systolic and diastolic function of the heart, functional capacity, lung function, sleep measures, quality of life and well-being (depression, anxiety, stress and sleep efficiency).

Discussion
The study will provide insights into the cardiovascular implications of COVID-19 and their malleability with a home-based physical activity intervention.

Trial registration
ClinicalTrials.gov NCT05492552. Registered on 7 April 2022.
The potential role of human islet amyloid polypeptide in type 2 diabetes mellitus and Alzheimer’s diseases
Authors: Alrouji Mohammed , Al-Kuraishy Hayder M. , Al-Gareeb Ali I. , Alexiou Athanasios , Papadakis Marios , Saad Hebatallah M. , Batiha Gaber El-Saber 
Published: May 2023

AbstractHuman Islet amyloid polypeptide (hIAPP) from pancreatic β cells in the islet of Langerhans has different physiological functions including inhibiting the release of insulin and glucagon. Type 2 diabetes mellitus (T2DM) is an endocrine disorder due to relative insulin insufficiency and insulin resistance (IR) is associated with increased circulating hIAPP. Remarkably, hIAPP has structural similarity with amyloid beta (Aβ) and can engage in the pathogenesis of T2DM and Alzheimer’s disease (AD). Therefore, the present review aimed to elucidate how hIAPP acts as a link between T2DM and AD. IR, aging and low β cell mass increase expression of hIAPP which binds cell membrane leading to the aberrant release of Ca2+and activation of the proteolytic enzymes leading to a series of events causing loss of β cells. Peripheral hIAPP plays a major role in the pathogenesis of AD, and high circulating hIAPP level increase AD risk in T2DM patients. However, there is no hard evidence for the role of brain-derived hIAPP in the pathogenesis of AD. Nevertheless, oxidative stress, mitochondrial dysfunction, chaperon-mediated autophagy, heparan sulfate proteoglycan (HSPG), immune response, and zinc homeostasis in T2DM could be the possible mechanisms for the induction of the aggregation of hIAPP which increase AD risk. In conclusion, increasing hIAPP circulating levels in T2DM patients predispose them to the development and progression of AD. Dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists attenuate AD in T2DM by inhibiting expression and deposition of hIAP.
Long-term mepolizumab treatment reduces relapse rates in super-responders with eosinophilic granulomatosis with polyangiitis
Authors: Masumoto Nami , Oshikata Chiyako , Nakadegawa Ryo , Motobayashi Yuto , Osada Reeko , Manabe Saki , Kaneko Takeshi , Tsurikisawa Naomi 
Published: May 2023

Abstract
Background
The mainstay of treatment for eosinophilic granulomatosis with polyangiitis (EGPA) is systemic corticosteroid therapy; some patients also receive intravenous immunoglobulins, other immunosuppressive agents, and biologics. Mepolizumab, an anti-interleukin-5 monoclonal antibody, induces remission and decreases the daily corticosteroid dose; however, the clinical efficacy of mepolizumab in EGPA and the prognosis with long-term treatment with this drug are unknown.

Methods
Seventy-one EGPA patients were treated at Hiratsuka City Hospital, Japan, between April 2018 and March 2022. We administered mepolizumab for a mean of 2.8 ± 1.7 years to 43 patients in whom remission could not be induced by conventional treatment. After excluding 18 patients who had received mepolizumab for less than 3 years, we classified 15 patients into a “super-responder group” (the daily dose of corticosteroids or other immunosuppressant could be decreased, or the interval between IVIG treatments could be prolonged) and 10 patients into a “responder group” (neither of these changes was achievable). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and other immunosuppressants, Birmingham Vasculitis Activity Score (BVAS), and relapse frequency before and after mepolizumab initiation were determined.

Results
Blood eosinophil count at diagnosis and the lowest serum IgG level before mepolizumab treatment were significantly higher in super-responders than in responders (p < 0.05). In super-responders, the prednisolone dose at last visit on mepolizumab treatment was lower than that before treatment (p < 0.01) and lower than that at last visit in the responders (p < 0.01). In both groups, peripheral blood eosinophil numbers and BVAS were lower after starting mepolizumab than before (p < 0.01). BVAS before mepolizumab (p < 0.05) and at last visit (p < 0.01) were lower in super-responders than in responders. Relapse rates every year after the start of mepolizumab were lower in super-responders than in responder groups (p < 0.01). In super-responders, relapse rates were lower during the 3 years following mepolizumab initiation (p < 0.01) and at last visit (p < 0.01) were significantly lower than after 1 year of treatment.

Conclusion
Mepolizumab treatment of super-responders sustainably reduced the relapse rate.
Hinokitiol-iron complex is a ferroptosis inducer to inhibit triple-negative breast tumor growth
Authors: Zhao Hongting , Zhang Meng , Zhang Jinghua , Sun Zichen , Zhang Wenxin , Dong Weichen , Cheng Chen , Yao Yongzhong , Li Kuanyu 
Published: May 2023

Abstract
Background
Ferroptosis is a unique cell death, dependent on iron and phospholipid peroxidation, involved in massive processes of physiopathology. Tremendous attention has been caught in oncology, particularly for those therapy-resistant cancers in the mesenchymal state prone to metastasis due to their exquisite vulnerability to ferroptosis. Therefore, a therapeutical ferroptosis inducer is now underway to be exploited.

Results
A natural compound, hinokitiol (hino), has been considered to be an iron chelator. We have a novel finding that hino complexed with iron to form Fe(hino)3 can function as a ferroptosis inducer in vitro. The efficiency, compared with the same concentration of iron, increases nearly 1000 folds. Other iron chelators, ferroptosis inhibitors, or antioxidants can inhibit Fe(hino)3-induced ferroptosis. The complex Fe(hino)3 efficacy is further confirmed in orthotopic triple-negative breast cancer (TNBC) tumor models that Fe(hino)3 significantly boosted lipid peroxidation to induce ferroptosis and significantly reduced the sizes of TNBC cell-derived tumors. The drug’s safety was also evaluated, and no detrimental side effects were found with the tested dosage.

Conclusions
When entering cells, the chelated iron by hinokitiol as a complex Fe(hino)3 is proposed to be redox-active to vigorously promote the production of free radicals via the Fenton reaction. Thus, Fe(hino)3 is a ferroptosis inducer and, therapeutically, exhibits anti-TNBC activity.
Research on real-time teachers’ facial expression recognition based on YOLOv5 and attention mechanisms
Authors: Zhong Hongmei , Han Tingting , Xia Wei , Tian Yan , Wu Libao 
Published: May 2023

AbstractStudying the real-time face expression state of teachers in class was important to build an objective classroom teaching evaluation system based on AI. However, the face-to-face communication in classroom conditions was a real-time process that operated on a millisecond time scale. Therefore, in order to quickly and accurately predict teachers’ facial expressions in real time, this paper proposed an improved YOLOv5 network, which introduced the attention mechanisms into the Backbone model of YOLOv5. In experiments, we investigated the effects of different attention mechanisms on YOLOv5 by adding different attention mechanisms after each CBS module in the CSP1_X structure of the Backbone part, respectively. At the same time, the attention mechanisms were incorporated at different locations of the Focus, CBS, and SPP modules of YOLOv5, respectively, to study the effects of the attention mechanism on different modules. The results showed that the network in which the coordinate attentions were incorporated after each CBS module in the CSP1_X structure obtained the detection time of 25 ms and the accuracy of 77.1% which increased by 3.5% compared with YOLOv5. It outperformed other networks, including Faster-RCNN, R-FCN, ResNext-101, DETR, Swin-Transformer, YOLOv3, and YOLOX. Finally, the real-time teachers’ facial expression recognition system was designed to detect and analyze the teachers’ facial expression distribution with time through camera and the teaching video.
Hyponatremia and aging-related diseases: key player or innocent bystander? A systematic review
Authors: Fratangelo Luigia , Nguyen Sylvain , D’Amelio Patrizia 
Published: May 2023

Abstract

Background
Hyponatremia is frequent in older age; whether it is a key player, a surrogate marker, or an innocent bystander in age-related diseases is still unclear.
Objective: To understand
the role of hyponatremia in falls, osteoporosis, fractures, and cognitive
impairment in old patients.

Method
Eligibility criteria for study inclusions were: written in English, peer-reviewed observational and intervention studies, clinical trial, prospective and retrospective controlled cohort studies, and case-controlled studies without limitations regarding the date of publication.
Information sources: Protocol available on the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021218389). MEDLINE, Embase, and PsycINFO were searched. Final search done on August 8, 2021.
Risk-of-bias assessment: Risk-of-Bias Assessment tool for Non-randomized Studies (RoBANS) and the Bradford Hill’s criteria for causality.

Results
Includes studies: One-hundred thirty-five articles retained for the revision.
Synthesis of results — Falls: Eleven studies were included. Strong association between hyponatremia and falls in all the studies was found. Osteoporosis and fractures: nineteen articles were included. The association between hyponatremia and osteoporosis is unclear. Cognitive impairment: Five articles were included. No association between hyponatremia and cognitive impairment was found.

Discussion
Interpretation: Falls, osteoporosis, and fractures are multifactorial. Hyponatremia is not temporally related with the outcomes; we suggest that hyponatremia may be regarded as a marker of unhealthy aging and a confounder instead of a causal factor or an innocent bystander for falls and fractures. Concerning cognitive impairment, there are no evidence supporting a real role of hyponatremia to be regarded as an innocent bystander in neurodegeneration.
Verifiable attribute-based keyword search scheme over encrypted data for personal health records in cloud
Authors: Sun Yuqin , Han Lidong , Bi Jingguo , Tan Xiao , Xie Qi 
Published: May 2023

AbstractPersonal health record (PHR) is a medical model in which patients can upload their medical records and define the access control by themselves. Since the limited local storage and the development of cloud computing, many PHR services have been outsourced to the cloud. In order to ensure the privacy of electronic medical records, patients intend to encrypt their health records before uploading them. However, encrypted PHR can not be accessed directly and not be retrieved by legitimate users. To solve these issues, in this article we propose a new searchable encryption scheme with ciphertext-policy attributes, which achieves fine-grained access control and exact keyword search over encrypted PHRs. Moreover, in our proposed scheme, the receiver can verify the integrity of the search result that the cloud server returns. Finally, we simulate our scheme, and the experiments show that our scheme has high practicability for cloud-based healthcare systems and has high efficiency in aspects of keyword search and results verification.