bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quercetin alleviates cyclophosphamide-induced premature ovarian insufficiency in mice by reducing mitochondrial oxidative stress and pyroptosis in granulosa cells
Authors: Chen Yun , Zhao Ying , Miao Chenyun , Yang Liuqing , Wang Ruye , Chen Bixia , Zhang Qin 
Published: December 2022

Abstract
Background
Exposure to cyclophosphamide (CTX) induces premature ovarian insufficiency (POI). Quercetin is a natural flavonoid that exhibits anti-inflammatory and antioxidant properties, and its antioxidant activity is correlated with POI. However, the mechanism underlying its protective role in CTX-induced ovarian dysfunction is unclear. This study aimed to explore whether quercetin can protect ovarian reserves by activating mitochondrial biogenesis and inhibiting pyroptosis.

Methods
Thirty-six female C57BL/6 mice were randomly subdivided into six groups. Except for the control group, all groups were injected with 90 mg/kg CTX to establish a POI model and further treated with coenzyme 10 or various doses of quercetin. The mice were sacrificed 48 h after 10 IU pregnant mare serum gonadotropin was injected four weeks after treatments. We used enzyme-linked immunosorbent assays to detect serum hormone expression and light and transmission electron microscopy to assess ovarian tissue morphology and mitochondria. Additionally, we tested oxidant and antioxidant levels in ovarian tissues and mitochondrial function in granulosa cells (GCs). The expression of mitochondrial biogenesis and pyroptosis-related proteins and mRNA was analyzed using western blotting and RT-qPCR.

Results
Quercetin elevated serum anti-Müllerian hormone, estradiol, and progesterone levels, decreased serum follicle-stimulating hormone and luteinizing hormone levels, and alleviated ovarian pathology. It reduced the mitochondrial DNA content and mitochondrial membrane potential. Furthermore, it upregulated ATP levels and the mRNA and protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), mitochondrial transcription factor A, and superoxide dismutase 2. In addition, it suppressed NOD-like receptor pyrin domain containing 3, caspase-1, interleukin-1β, and gasdermin D levels in the GCs of POI mice.

Conclusions
Quercetin protected the ovarian reserve from CTX-induced ovarian damage by reversing mitochondrial dysfunction and activating mitochondrial biogenesis via the PGC1-α pathway. Moreover, quercetin may improve ovarian functions by downregulating pyroptosis in the CTX-induced POI model. Thus, quercetin can be considered a potential agent for treating POI.
A good use of time? Providing evidence for how effort is invested in primary and secondary outcome data collection in trials
Authors: Gardner Heidi , Elfeky Adel , Pickles David , Dawson Annabel , Gillies Katie , Warwick Violet , Treweek Shaun 
Published: December 2022

Abstract
Background
Data collection is a substantial part of trial workload for participants and staff alike. How these hours of work are spent is important because stakeholders are more interested in some outcomes than others. The ORINOCO study compared the time spent collecting primary outcome data to the time spent collecting secondary outcome data in a cohort of trials.

Methods
We searched PubMed for phase III trials indexed between 2015 and 2019. From these, we randomly selected 120 trials evaluating a therapeutic intervention plus an additional random selection of 20 trials evaluating a public health intervention. We also added eligible trials from a cohort of 189 trials in rheumatology that had used the same core outcome set.
We then obtained the time taken to collect primary and secondary outcomes in each trial. We used a hierarchy of methods that included data in trial reports, contacting the trial team and approaching individuals with experience of using the identified outcome measures. We calculated the primary to secondary data collection time ratio and notional data collection cost for each included trial.

Results
We included 161 trials (120 phase III; 21 core outcome set; 20 public health), which together collected 230 primary and 688 secondary outcomes. Full primary and secondary timing data were obtained for 134 trials (100 phase III; 17 core outcome set; 17 public health). The median time spent on primaries was 56.1 h (range: 0.0–10,746.7, IQR: 226.89) and the median time spent on secondaries was 190.7 hours (range: 0.0–1,356,832.9, IQR: 617.6). The median primary to secondary data collection time ratio was 1.0:3.0 (i.e. for every minute spent on primary outcomes, 3.0 were spent on secondaries). The ratio varied by trial type: phase III trials were 1.0:3.1, core outcome set 1.0:3.4 and public health trials 1.0:2.2. The median notional overall data collection cost was £8015.73 (range: £52.90–£31,899,140.70, IQR: £20,096.64).

Conclusions
Depending on trial type, between two and three times as much time is spent collecting secondary outcome data than collecting primary outcome data. Trial teams should explicitly consider how long it will take to collect the data for an outcome and decide whether that time is worth it given importance of the outcome to the trial.
A mental health-informed, online health promotion programme targeting physical activity and healthy eating for adults aged 60+ years: study protocol for the MovingTogether randomised controlled trial
Authors: Mastrogiovanni Chiara , Rosenbaum Simon , Delbaere Kim , Tiedemann Anne , Teasdale Scott , McGavin Annaliese , Briggs Nancy , McKeon Grace 
Published: December 2022

Abstract
Background
The COVID-19 pandemic and associated social distancing regulations have led to an increased risk of social isolation and physical inactivity, particularly among older adults. The benefits of physical activity for reducing fall risk and improving mood and mental functioning have been well documented. The aim of this trial is to investigate the effect of the MovingTogether programme on psychological distress (primary outcome) and physical activity, social capital, cognition, concern about falling, loneliness, physical functioning, quality of life and physical activity enjoyment (secondary outcomes).

Methods
A randomised controlled trial with a waitlist control will be conducted, recruiting 80 adults aged 60+ years with access to Facebook and a computer or tablet and not currently meeting the aerobic physical activity guidelines. Randomisation will be completed using REDCap. The intervention group (n = 40) will join a private Facebook group where allied health facilitators will provide targeted healthy lifestyle education throughout the 10-week programme with weekly telehealth group calls. Intervention participants will also be provided access to tailored strength and aerobic exercise guidance and an evidence-based eHealth balance exercise programme. Psychological distress and secondary outcomes will be assessed at baseline, 11 weeks (post-intervention) and 16 weeks (1-month follow-up). Linear mixed models will be applied for each outcome measure as per an intention-to-treat approach to determine the between-group differences. Secondary analyses are planned in people with greater adherence and those with higher psychological distress.

Discussion
COVID-19 has highlighted the need for scalable, effective and novel methods to improve and protect the health of older adults. The integration of an evidence-based fall prevention programme with a mental health-informed online health promotion programme may help to improve mental and physical health outcomes among older adults.

Trial registration
Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001322820p. Registered on 29 September 2021
Effectiveness of a 6-week specific rehabilitation program combining education and exercises on walking capacity in patients with lumbar spinal stenosis with neurogenic claudication: a randomized controlled clinical trial protocol
Authors: Houle Mariève , Tétreau Charles , Châtillon Claude-Édouard , Marchand Andrée-Anne , Descarreaux Martin 
Published: December 2022

AbstractBackgroundLumbar spinal stenosis (LSS) causing neurogenic claudication (NC) is a leading cause of disability which is intimately related to a decrease in walking capacity. Walking limitation has negative physical and mental impacts on patients. Recent guidelines recommend the use of conservative treatment options such as exercises before considering surgery. Unfortunately, dedicated healthcare resources for the conservative management of patients with LSS causing NC are uncommon. Thus, it is important to develop accessible and specific rehabilitation programs aimed at improving patients’ self-management, especially with regard to walking capacity. The aim of this study is to evaluate the effectiveness of a 6-week specific rehabilitation program combining education and exercises on walking capacity in patients with LSS causing NC.Methods/designThis is a prospective randomized controlled parallel-group clinical trial. Sixty-six patients with LSS causing NC will be recruited from identified clinics and local advertisements. The intervention group will receive standardized education and specific exercises while the control group will only receive a standardized education. The program in both groups will last for 6 weeks with 5 evaluation time points (baseline, week 2, week 4, week 6, and week 12). The primary outcome will be walking capacity measured with the Self-Paced Walking Test, and the secondary outcomes will be back and leg pain intensity, LSS-related disability, self-efficacy, level of physical activity, anxiety, depression, gait pattern characteristics, balance, and global perceived change.DiscussionThis study will assess the effectiveness of a 6-week specific rehabilitation program combining education and exercises on walking capacity in patients with LSS causing NC. By measuring objective gait pattern characteristics, the study will also provide new information about the impact of NC on gait pattern that could eventually improve the evaluation and the management of LSS.Trial registrationClinicalTrials.govNCT05513326. Registered on August 22, 2022
Early use of airway pressure release ventilation in acute respiratory distress syndrome induced by coronavirus disease 2019: a case report
Authors: Sinatra Jadeny , Salim Ronnie Wirawan , Tanoto Epifanus Arie , Hariyanto Hori 
Published: December 2022

Abstract
Background
Coronavirus disease 2019 is a highly transmissible and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2, a novel coronavirus that was identified in early January 2020 in Wuhan, China, and has become a pandemic disease worldwide. The symptoms of coronavirus disease 2019 range from asymptomatic to severe respiratory failure. In moderate and severe cases, oxygen therapy is needed. In severe cases, high-flow nasal cannula, noninvasive ventilation, and invasive mechanical ventilation are needed. Many ventilation methods in mechanical ventilation can be used, but not all are suitable for coronavirus disease 2019 patients. Airway pressure release ventilation, which is one of the mechanical ventilation methods, can be considered for patients with moderate-to-severe acute respiratory distress syndrome. It was found that oxygenation in the airway pressure release ventilation method was better than in the conventional method. How about airway pressure release ventilation in coronavirus disease 2019 patients? We report a case of confirmed coronavirus disease 2019 in which airway pressure release ventilation mode was used.

Case presentation
In this case study, we report a 74-year-old Chinese with a history of hypertension and uncontrolled diabetes mellitus type 2. He came to our hospital with the chief complaint of difficulty in breathing. He was fully awake with an oxygen saturation of 82% on room air. The patient was admitted and diagnosed with severe coronavirus disease 2019, and he was given a nonrebreathing mask at 15 L per minute, and oxygen saturation went back to 95%. After a few hours with a nonrebreathing mask, his condition worsened. On the third day after admission, saturation went down despite using noninvasive ventilation. We decided to intubate the patient and used airway pressure release ventilation mode. Finally, after 14 days of being intubated, the patient could be extubated and discharged after 45 days of hospitalization.

Conclusion
Early use of airway pressure release ventilation may be considered as one of the ventilation strategies to treat severe coronavirus disease 2019 acute respiratory distress syndrome. Although reports on airway pressure release ventilation and protocols on its initiation and titration methods are limited, it may be worthwhile to consider, given its known ability to maximize alveolar recruitment, preserve alveolar epithelial integrity, and surfactant, all of which are crucial for handling the “fragile” lungs of coronavirus disease 2019 patients.
Small molecule-mediated rapid maturation of human induced pluripotent stem cell-derived cardiomyocytes
Authors: Chirico Nino , Kessler Elise L. , Maas Renée G. C. , Fang Juntao , Qin Jiabin , Dokter Inge , Daniels Mark , Šarić Tomo , Neef Klaus , Buikema Jan-Willem , Lei Zhiyong , Doevendans Pieter A. , Sluijter Joost P. G. , van Mil Alain 
Published: December 2022

Abstract
Background
Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) do not display all hallmarks of mature primary cardiomyocytes, especially the ability to use fatty acids (FA) as an energy source, containing high mitochondrial mass, presenting binucleation and increased DNA content per nuclei (polyploidism), and synchronized electrical conduction. This immaturity represents a bottleneck to their application in (1) disease modelling—as most cardiac (genetic) diseases have a middle-age onset—and (2) clinically relevant models, where integration and functional coupling are key. So far, several methods have been reported to enhance iPSC-CM maturation; however, these protocols are laborious, costly, and not easily scalable. Therefore, we developed a simple, low-cost, and rapid protocol to promote cardiomyocyte maturation using two small molecule activators of the peroxisome proliferator-activated receptor β/δ and gamma coactivator 1-alpha (PPAR/PGC-1α) pathway: asiatic acid (AA) and GW501516 (GW).

Methods and Results
Monolayers of iPSC-CMs were incubated with AA or GW every other day for ten days resulting in increased expression of FA metabolism-related genes and markers for mitochondrial activity. AA-treated iPSC-CMs responsiveness to the mitochondrial respiratory chain inhibitors increased and exhibited higher flexibility in substrate utilization. Additionally, structural maturity improved after treatment as demonstrated by an increase in mRNA expression of sarcomeric-related genes and higher nuclear polyploidy in AA-treated samples. Furthermore, treatment led to increased ion channel gene expression and protein levels.

Conclusions
Collectively, we developed a fast, easy, and economical method to induce iPSC-CMs maturation via PPAR/PGC-1α activation. Treatment with AA or GW led to increased metabolic, structural, functional, and electrophysiological maturation, evaluated using a multiparametric quality assessment.
Efficient bone regeneration of BMP9-stimulated human periodontal ligament stem cells (hPDLSCs) in decellularized bone matrix (DBM) constructs to model maxillofacial intrabony defect repair
Authors: Zhang Yuxin , Luo Wenping , Zheng Liwen , Hu Jing , Nie Li , Zeng Huan , Tan Xi , Jiang Yucan , Li Yeming , Zhao Tianyu , Yang Zhuohui , He Tong-Chuan , Zhang Hongmei 
Published: December 2022

AbstractBackgroundBMP9-stimulated DPSCs, SCAPs and PDLSCs are effective candidates for repairing maxillofacial bone defects in tissue engineering, while the most suitable seed cell source among these three hDMSCs and the optimal combination of most suitable type of hDMSCs and BMP9 have rarely been explored. Moreover, the orthotopic maxillofacial bone defect model should be valuable but laborious and time-consuming to evaluate various candidates for bone regeneration. Thus, inspired from the maxillofacial bone defects and the traditional in vivo ectopic systems, we developed an intrabony defect repair model to recapitulate the healing events of orthotopic maxillofacial bone defect repair and further explore the optimized combinations of most suitable hDMSCs and BMP9 for bone defect repair based on this modified ectopic system.MethodsIntrabony defect repair model was developed by using decellularized bone matrix (DBM) constructs prepared from the cancellous part of porcine lumbar vertebral body. We implanted DBM constructs subcutaneously on the flank of each male NU/NU athymic nude mouse, followed by directly injecting the cell suspension of different combinations of hDMSCs and BMP9 into the central hollow area of the constructs 7 days later. Then, the quality of the bony mass, including bone volume fraction (BV/TV), radiographic density (in Hounsfield units (HU)) and the height of newly formed bone, was measured by micro-CT. Furthermore, the H&E staining and immunohistochemical staining were performed to exam new bone and new blood vessel formation in DBM constructs.ResultsBMP9-stimulated periodontal ligament stem cells (PDLSCs) exhibited the most effective bone regeneration among the three types of hDMSCs in DBM constructs. Furthermore, an optimal dose of PDLSCs with a specific extent of BMP9 stimulation was confirmed for efficacious new bone and new blood vessel formation in DBM constructs.ConclusionsThe reported intrabony defect repair model can be used to identify optimized combinations of suitable seed cells and biological factors for bone defect repair and subsequent development of efficacious bone tissue engineering therapies.
Ostrowski-type inequalities pertaining to Atangana–Baleanu fractional operators and applications containing special functions
Authors: Sahoo Soubhagya Kumar , Kodamasingh Bibhakar , Kashuri Artion , Aydi Hassen , Ameer Eskandar 
Published: December 2022

AbstractThe objective of this article is to incorporate the concept of the Ostrowski inequality with the Atangana–Baleanu fractional integral operator. A novel integral identity for twice-differentiable functions is established after a rigorous investigation of several basic definitions and existing ideas related to inequalities and fractional calculus. Following that, numerous Ostrowski-type inequalities are provided based on this identity, which uses Mittag–Leffler as its kernel structure. Some specific applications, such as q-digamma functions and modified Bessel functions, are also investigated. Choosing $s=1$
s
=
1
, we also analyze new results for convex functions as special cases. Our findings corroborate some well-documented inequalities.
Steady states of a diffusive predator-prey model with prey-taxis and fear effect
Authors: Cao Jianzhi , Li Fang , Hao Pengmiao 
Published: December 2022

AbstractIn this paper, a diffusive predator-prey system with a prey-taxis response subject to Neumann boundary conditions is considered. The stability, the Hopf bifurcation, the existence of nonconstant steady states, and the stability of the bifurcation solutions of the system are analyzed. It is proved that a high level of prey-taxis can stabilize the system, the stability of the positive equilibrium is changed when χ crosses $\chi _{0}$

χ
0

, and the Hopf bifurcation occurs for the small s. The system admits nonconstant positive solutions around $(\bar{u}, \bar{v}, \chi _{i} )$
(

u
¯

,

v
¯

,

χ
i

)
, the stability of bifurcating solutions are controlled by $\int _{\Omega} \Phi _{i}^{3} \,\mathrm{d}x$

∫
Ω

Φ
i
3

d
x
and $\int _{\Omega} \Phi _{i}^{4} \,\mathrm{d}x$

∫
Ω

Φ
i
4

d
x
. Finally, numerical simulation results are carried out to verify the theoretical findings.
Violence Detection Approach based on Cloud Data and Neutrosophic Cognitive Maps
Authors: Wajid Mohammad Saif , Terashima-Marin Hugo , Paul Rad Peyman Najafirad , Wajid Mohd Anas 
Published: December 2022

AbstractViolence has remained a momentous problem since time immemorial. Various scientific studies are conducted in the recent past to identify the stimuli causing violent behavior among the masses and to achieve the target of cloud data protection. Given the inherent ambiguity or indeterminacy in human behaviour, this study in the area of violence detection appears to be effective, as it finds a variety of stimuli and character qualities that contribute to violent conduct among masses. This uncertainty of traits causing violence can easily be seen in surveillance data present over the cloud and also from the data collected using academic research. Therefore, for the purpose of identifying violent behavior we have considered the factors (data) from existing research and from data over clouds. The factors that lead to violent behavior and are identified by algorithms running over clouds are termed as determinate or certain factors. The factors that were not considered and least identified by the cloud algorithms and given less importance are termed indeterminate factors or uncertain factors. The indeterminate factors are also considered based on the expert’s opinion where the experts are not in a condition to provide a clear stance or when they are neutral in their opinion. Tests are performed using Neutrosophic Cognitive Maps (NCMs) to model the violent behavior taking into consideration both determinate and indeterminate factors. Earlier these tests were performed using Fuzzy Cognitive Maps (FCMs) where indeterminate or uncertain factors were not considered. Therefore, we provide a brief comparison between NCMs and FCMs and show how effective NCMs are when we need to consider the uncertainty of concepts while carrying out tests for identifying violent behavior. Later results are obtained by forming a Neutrosophic adjacency matrix which is evaluated using the concepts of linear algebra. The obtained results in the form of 1 ∗ nvector (1 I I I I 1 I 1 I I I I I I I I I I I ) clearly shows the presence of indeterminate factor‘I’in the vector which was absent in earlier models when designed using FCMs. This shows how these indeterminate or uncertain factors play a significant role in cultivating violent behavior which was not shown in the previous study. The study is significant since it takes into account factors from cloud data, experts’ opinions, and also from literature, and shows how these factors are taken into consideration at the data level itself so that they will not impact the modeling stage, and machine learning algorithms will perform well because uncertain and indeterminate information is taken care of at training phase itself. Hence uncertainty could be reduced in machine learning algorithms and in the overall recognition of violent behavior.