bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a new adapted QuinteT Recruitment Intervention (QRI-Two) for rapid application to RCTs underway with enrolment shortfalls—to identify previously hidden barriers and improve recruitment
Authors: Donovan Jenny L. , Jepson Marcus , Rooshenas Leila , Paramasivan Sangeetha , Mills Nicola , Elliott Daisy , Wade Julia , Reda Domenic , Blazeby Jane M. , Moghanaki Drew , Hwang E. Shelley , Davies Louise 
Published: April 2022

Abstract
Background
Many randomised controlled trials (RCTs) struggle to recruit, despite valiant efforts. The QRI (QuinteT Recruitment Intervention) uses innovative research methods to optimise recruitment by revealing previously hidden barriers related to the perceptions and experiences of recruiters and patients, and targeting remedial actions. It was designed to be integrated with RCTs anticipating difficulties at the outset. A new version of the intervention (QRI-Two) was developed for RCTs already underway with enrolment shortfalls.

Methods
QRIs in 12 RCTs with enrolment shortfalls during 2007–2017 were reviewed to document which of the research methods used could be rapidly applied to successfully identify recruitment barriers. These methods were then included in the new streamlined QRI-Two intervention which was applied in 20 RCTs in the USA and Europe during 2018–2019. The feasibility of the QRI-Two was investigated, recruitment barriers and proposed remedial actions were documented, and the QRI-Two protocol was finalised.

Results
The review of QRIs from 2007 to 2017 showed that previously unrecognised recruitment barriers could be identified but data collection for the full QRI required time and resources usually unavailable to ongoing RCTs. The streamlined QRI-Two focussed on analysis of screening/accrual data and RCT documents (protocol, patient-information), with discussion of newly diagnosed barriers and potential remedial actions in a workshop with the RCT team. Four RCTs confirmed the feasibility of the rapid application of the QRI-Two. When the QRI-Two was applied to 14 RCTs underway with enrolment shortfalls, an array of previously unknown/underestimated recruitment barriers related to issues such as equipoise, intervention preferences, or study presentation was identified, with new insights into losses of eligible patients along the recruitment pathway. The QRI-Two workshop enabled discussion of the newly diagnosed barriers and potential remedial actions to improve recruitment in collaboration with the RCT team. As expected, the QRI-Two performed less well in six RCTs at the start-up stage before commencing enrolment.

Conclusions
The QRI-Two can be applied rapidly, diagnose previously unrecognised recruitment barriers, and suggest remedial actions in RCTs underway with enrolment shortfalls, providing opportunities for RCT teams to develop targeted actions to improve recruitment. The effectiveness of the QRI-Two in improving recruitment requires further evaluation.
A randomised controlled trial investigating the clinical and cost-effectiveness of Alpha-Stim AID cranial electrotherapy stimulation (CES) in patients seeking treatment for moderate severity depression in primary care (Alpha-Stim-D Trial)
Authors: Patel Shireen , Boutry Clement , Patel Priya , Craven Michael P. , Guo Boliang , Zafar Azhar , Kai Joe , Smart David , Butler Debbie , Higton Fred , McNaughton Rebecca , Briley Paul M. , Griffiths Chris , Nixon Neil , Sayal Kapil , Morriss Richard 
Published: April 2022

Abstract
Background
Major depression is the second leading cause of years lost to disability worldwide and is a leading contributor to suicide. However, first-line antidepressants are only fully effective for 33%, and only 40% of those offered psychological treatment attend for two sessions or more. Views gained from patients and primary care professionals are that greater treatment uptake might be achieved if people with depression could be offered alternative and more accessible treatment options. Although there is evidence that the Alpha-Stim Anxiety Insomnia and Depression (AID) device is safe and effective for anxiety and depression symptoms in people with anxiety disorders, there is much less evidence of efficacy in major depression without anxiety. This study investigates the effectiveness of the Alpha-Stim AID device, a cranial electrotherapy stimulation (CES) treatment that people can safely use independently at home. The device provides CES which has been shown to increase alpha oscillatory brain activity, associated with relaxation.

Methods
The aim of this study is to investigate the clinical and cost-effectiveness of Alpha-Stim AID in treatment-seeking patients (aged 16 years upwards) with moderate to moderately severe depressive symptoms in primary care. The study is a multi-centre parallel-group, double-blind, non-commercial, randomised controlled superiority trial. The primary objective of the study is to examine the clinical efficacy of active daily use of 8 weeks of Alpha-Stim AID versus sham Alpha-Stim AID on depression symptoms at 16 weeks (8 weeks after the end of treatment) in people with moderate severity depression. The primary outcome is the 17-item Hamilton Depression Rating Scale at 16 weeks. All trial and treatment procedures are carried out remotely using videoconferencing, telephone and postal delivery considering the COVID-19 pandemic restrictions.

Discussion
This study is investigating whether participants using the Alpha-Stim AID device display a reduction in depressive symptoms that can be maintained over 8 weeks post-treatment. The findings will help to determine whether Alpha-Stim AID should be recommended, including being made available in the NHS for patients with depressive symptoms.

Trial registration
ISRTCN ISRCTN11853110. Registered on 14 August 2020
Comparing Sugarbaker versus keyhole mesh technique for open retromuscular parastomal hernia repair: study protocol for a registry-based randomized controlled trial
Authors: Miller Benjamin T. , Thomas Jonah D. , Tu Chao , Costanzo Adele , Beffa Lucas R. A. , Krpata David M. , Prabhu Ajita S. , Rosen Michael J. , Petro Clayton C. 
Published: April 2022

Abstract
Background
Parastomal hernia, common after stoma creation, negatively impacts patient quality of life. For patients with a permanent stoma, durable parastomal hernia repair remains a challenge, with few high-quality studies for guidance. An alternative to open retromuscular parastomal hernia repair with retromuscular “keyhole” mesh is the recent Sugarbaker modification. We aim to compare these two techniques in a head-to-head prospective study.

Methods
This is a registry-based randomized controlled trial designed to investigate whether the retromuscular Sugarbaker technique is superior to the retromuscular keyhole technique for parastomal hernia repair. The primary study endpoint is parastomal hernia recurrence at 2 years. Secondary endpoints include hospital length-of-stay, readmission, wound morbidity, mesh-related complications, re-operation, all 30-day morbidity, and patient-reported outcomes, including hernia-related quality of life, stoma-specific quality of life, pain, and decision regret.

Discussion
Based on the post hoc analysis of a recent randomized controlled trial, we hypothesize that the retromuscular Sugarbaker technique will reduce parastomal hernia recurrence by 20% at 2 years compared to the retromuscular keyhole mesh technique. The results of this study may provide evidence-based guidance for surgeons repairing parastomal hernias.

Trial registration
ClinicalTrials.gov NCT03972553. Registered on 3 June 2019
The structural diversity of CACTA transposons in genomes of Chenopodium (Amaranthaceae, Caryophyllales) species: specific traits and comparison with the similar elements of angiosperms
Authors: Belyayev Alexander , Josefiová Jiřina , Jandová Michaela , Kalendar Ruslan , Mahelka Václav , Mandák Bohumil , Krak Karol 
Published: April 2022

AbstractBackgroundCACTA transposable elements (TEs) comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) transposons. Over recent decades, CACTA elements were widely identified in species from the plant, fungi, and animal kingdoms, but sufficiently studied in the genomes of only a few model species although non-model genomes can bring additional and valuable information. It primarily concerned the genomes of species belonging to clades in the base of large taxonomic groups whose genomes, to a certain extent, can preserve relict and/or possesses specific traits. Thus, we sought to investigate the genomes ofChenopodium(Amaranthaceae,Caryophyllales) species to unravel the structural variability of CACTA elements.Caryophyllalesis a separate branch of Angiosperms and until recently the diversity of CACTA elements in this clade was unknown.ResultsApplication of the short-read genome assembly algorithm followed by analysis of detected complete CACTA elements allowed for the determination of their structural diversity in the genomes of 22Chenopodium albumaggregate species. This approach yielded knowledge regarding: (i) the coexistence of two CACTA transposons subtypes in single genome; (ii) gaining of additional protein conserved domains within the coding sequence; (iii) the presence of captured gene fragments, including key genes for flower development; and (iv)) identification of captured satDNA arrays. Wide comparative database analysis revealed that identified events are scattered through Angiosperms in different proportions.ConclusionsOur study demonstrated that while preserving the basic element structure a wide range of coding and non-coding additions to CACTA transposons occur in the genomes ofC. albumaggregate species. Ability to relocate additions inside genome in combination with the proposed novel functional features of structural-different CACTA elements can impact evolutionary trajectory of the host genome.
Late metachronous cerebral metastasis of pancreatic adenocarcinoma of the tail of the pancreas: a case report
Authors: Papadimitriou Kyriakos , Kiss-Bodolay Daniel , Hedjoudje Abderrahmane , Millan Diego San , Simonin Alexandre , Fournier Jean-Yves , Huscher Karen 
Published: April 2022

Abstract
Background
Pancreatic cancer is one of the leading causes of cancer mortality and one of the most lethal malignant neoplasms worldwide. It is known for its local tumor extension to the liver; other common sites include the lung, distant lymph nodes, and bone. Brain metastases are extremely rare and represent less than 0.6% of all brain metastases.

Case report
We report the case of a 66-year-old Caucasian female known to have adenocarcinoma of the tail of the pancreas treated with chemotherapy. During follow-up, thoracoabdominal computed tomography scans did not reveal any residual tumor or any metastasis. Moreover, tumor markers were within normal limits. She presented to the emergency department of our institution following an episode of a generalized tonic–clonic seizure 5 years following the initial diagnosis. Brain magnetic resonance imaging revealed an expansive left frontal intraaxial lesion compatible with high-grade glioma. The patient underwent surgical treatment. Histological examination revealed pancreatic metastasis.

Conclusions
Thought to be rare, metachronous cerebral pancreatic metastasis should be kept in mind in patients with pancreatic cancer. Early diagnosis and complete surgical resection play a key role in the survival of these patients.
Episodic apnea: gastroesophageal reflux associated with gastric organo-axial malrotation: a case report
Authors: Turk Sena , Gokce Sule , Koc Feyza Umay 
Published: April 2022

Abstract
Background
Gastroesophageal reflux is a normal physiologic process occurring several times a day in healthy infants. On the other hand, symptoms such as failure to thrive, feeding or sleeping problems, chronic respiratory distress, persistent forceful vomiting, and choking may indicate reflux associated with underlying anatomic, neurological, or infectious abnormalities. Gastric malrotation is an extremely rare disorder in the pediatric population and one of the anatomic causes associated with severe reflux, which could lead to serious complications. In such cases, life-threatening symptoms overlapping with other diseases cause delayed diagnosis and treatment.

Case presentation
We report a 2.5-month-old white girl diagnosed with gastric malrotation-related reflux, which caused inadequate weight gain, feeding difficulties, episodes of apnea with cyanosis, and choking after successive coughing, hence previously misdiagnosed as epilepsy and pertussis.

Conclusion
Life-threatening symptoms in an infant with reflux suggest anatomic, neurological, or infectious conditions. Gastric malrotation is more common than generally thought and specifically looked for in young children with severe reflux symptoms, and should be diagnosed and treated as soon as possible.
Emerging role of exosomes in the pathology of chronic obstructive pulmonary diseases; destructive and therapeutic properties
Authors: Rajabi Hadi , Konyalilar Nur , Erkan Sinem , Mortazavi Deniz , Korkunc Seval Kubra , Kayalar Ozgecan , Bayram Hasan , Rahbarghazi Reza 
Published: April 2022

AbstractChronic obstructive pulmonary disease (COPD) is known as the third leading cause of human death globally. Enhanced chronic inflammation and pathological remodeling are the main consequences of COPD, leading to decreased life span. Histological and molecular investigations revealed that prominent immune cell infiltration and release of several cytokines contribute to progressive chronic remodeling. Recent investigations have revealed that exosomes belonging to extracellular vesicles are involved in the pathogenesis of COPD. It has been elucidated that exosomes secreted from immune cells are eligible to carry numerous pro-inflammatory factors exacerbating the pathological conditions. Here, in this review article, we have summarized various and reliable information about the negative role of immune cell-derived exosomes in the remodeling of pulmonary tissue and airways destruction in COPD patients.
PA1 participates in the maintenance of blood–testis barrier integrity via cooperation with JUN in the Sertoli cells of mice
Authors: Liu Bo , Liu Chao , Ma Binfang , Zhang Ruidan , Zhao Zhiwei , Xiao Sai , Cao Wanjun , Ma Yanjie , Zhu Guozhang , Li Wei , Li Zhen 
Published: April 2022

Abstract
Background
The blood–testis barrier (BTB) is essential to the microenvironment of spermatogenesis, and Sertoli cells provide the cellular basis for BTB construction. Numerous nuclear transcription factors have been identified to be vital for the proper functioning of Sertoli cells. PA1 has been reported to play important roles during diverse biological processes, yet its potential function in male reproduction is still unknown.

Results
Here, we show that PA1 was highly expressed in human and mouse testis and predominantly localized in the nuclei of Sertoli cells. Sertoli cell-specific Pa1 knockout resulted in an azoospermia-like phenotype in mice. The knockout of this gene led to multiple defects in spermatogenesis, such as the disorganization of the cytoskeleton during basal and apical ectoplasmic specialization and the disruption of the BTB. Further transcriptomic analysis, together with Cut-Tag results of PA1 in Sertoli cells, revealed that PA1 could affect the expression of a subset of genes that are essential for the normal function of Sertoli cells, including those genes associated with actin organization and cellular junctions such as Connexin43 (Cx43). We further demonstrated that the expression of Cx43 depended on the interaction between JUN, one of the AP-1 complex transcription factors, and PA1.

Conclusion
Overall, our findings reveal that PA1 is essential for the maintenance of BTB integrity in Sertoli cells and regulates BTB construction-related gene expression via transcription factors. Thus, this newly discovered mechanism in Sertoli cells provides a potential diagnostic or even therapeutic target for some individuals with azoospermia.
Rebuilding hippocampus neural circuit with hADSC-derived neuron cells for treating ischemic stroke
Authors: Wang Jian , Hao Rui , Jiang Tianfang , Guo Xuanxuan , Zhou Fei , Cao Limei , Gao Fengjuan , Wang Guangming , Wang Juan , Ning Ke , Zhong Chunlong , Chen Xu , Huang Ying , Xu Jun , Gao Shane 
Published: April 2022

AbstractBackgroundHuman adipose-derived stem cells (hADSCs) have been demonstrated to be a promising autologous stem cell source for treating various neuronal diseases. Our study indicated that hADSCs could be induced into neuron-like cells in a stepwise manner that are characterized by the positive expression of MAP2, SYNAPSIN 1/2, NF-200, and vGLUT and electrophysiological activity. We first primed hADSCs into neuron-like cells (hADSC-NCs) and then intracerebrally transplanted them into MCAO reperfusion mice to further explore their in vivo survival, migration, integration, fate commitment and involvement in neural circuit rebuilding.ResultsThe hADSC-NCs survived well and transformed into MAP2-positive, Iba1- or GFAP-negative cells in vivo while maintaining some proliferative ability, indicated by positive Ki67 staining after 4 weeks. hADSC-NCs could migrate to multiple brain regions, including the cortex, hippocampus, striatum, and hypothalamus, and further differentiate into mature neurons, as confirmed by action potential elicitation and postsynaptic currents. With the aid of a cell suicide system, hADSC-NCs were proven to have functionally integrated into the hippocampal memory circuit, where they contributed to spatial learning and memory rescue, as indicated by LTP improvement and subsequent GCV-induced relapse. In addition to infarction size shrinkage and movement improvement, MCAO-reperfused mice showed bidirectional immune modulation, including inhibition of the local proinflammatory factors IL-1α, IL-1β, IL-2, MIP-1β and promotion proinflammatory IP-10, MCP-1, and enhancement of the anti-inflammatory factors IL-15.ConclusionOverall, hADSC-NCs used as an intermediate autologous cell source for treating stroke can rebuild hippocampus neuronal circuits through cell replacement.
UBIAD1 alleviates ferroptotic neuronal death by enhancing antioxidative capacity by cooperatively restoring impaired mitochondria and Golgi apparatus upon cerebral ischemic/reperfusion insult
Authors: Huang Yan , Liu Jianyang , He Jialin , Hu Zhiping , Tan Fengbo , Zhu Xuelin , Yuan Fulai , Jiang Zheng 
Published: April 2022

AbstractBackgroundNeuronal death due to over-oxidative stress responses defines the pathology of cerebral ischemic/reperfusion (I/R) insult. Ferroptosis is a form of oxidative cell death that is induced by disruption of the balance between antioxidants and pro-oxidants in cells. However, the potential mechanisms responsible for cerebral I/R-induced ferroptotic neuronal death have not been conclusively determined. UBIAD1, is a newly identified antioxidant enzyme that catalyzes coenzyme Q10 (CoQ10) and vitamin K2 biosynthesis in the Golgi apparatus membrane and mitochondria, respectively. Even though UBIAD1 is a significant mediator of apoptosis in cerebral I/R challenge, its roles in ferroptotic neuronal death remain undefined. Therefore, we investigated whether ferroptotic neuronal death is involved in cerebral I/R injury. Further, we evaluated the functions and possible mechanisms of UBIAD1 in cerebral I/R-induced ferroptotic neuronal death, with a major focus on mitochondrial and Golgi apparatus dysfunctions.ResultsFerroptosis occurred in cerebral I/R. Ferroptotic neuronal death promoted cerebral I/R-induced brain tissue injury and neuronal impairment. UBIAD1 was expressed in cerebral tissues and was localized in neurons, astrocytes, and microglia. Under cerebral I/R conditions overexpressed UBIAD1 significantly suppressed lipid peroxidation and ferroptosis. Moreover, upregulated UBIAD1 protected against brain tissue damage and neuronal death by alleviating I/R-mediated lipid peroxidation and ferroptosis. However, UBIAD1 knockdown reversed these changes. Enhanced UBIAD1-mediated ferroptosis elevated the antioxidative capacity by rescuing mitochondrial and Golgi apparatus dysfunction in cerebral I/R-mediated neuronal injury. They improved the morphology and biofunctions of the mitochondria and Golgi apparatus, thereby elevating the levels of SOD, T-AOC and production of CoQ10, endothelial nitric oxide synthase (eNOS)-regulated nitric oxide (NO) generation as well as suppressed MDA generation.ConclusionsThe neuroprotective agent, UBIAD1, modulates I/R-mediated ferroptosis by restoring mitochondrial and Golgi apparatus dysfunction in damaged brain tissues and neurons, thereby enhancing antioxidative capacities. Moreover, the rescue of impaired mitochondrial and Golgi apparatus as a possible mechanism of regulating ferroptotic neuronal death is a potential treatment strategy for ischemic stroke.Graphical Abstract
Joint optimization of dynamic resource allocation and packet scheduling for virtual switches in cognitive internet of vehicles
Authors: Wang Yang , Wang Xiong , Huang Zhuobin , Li Wei , Xu Shizhong 
Published: April 2022

AbstractThe rapidly evolving machine learning technologies have reshaped the transportation system and played an essential role in the Cognitive Internet of Vehicles (CIoV). Most of the cognitive services are computation-intensive or storage-intensive, and thus they are usually deployed in edge or cloud data centers. In today’s data center networks, the virtual machines hosted in a server are connected to a virtual switch responsible for forwarding all packets for the cognitive services deployed on the virtual machines. Therefore, the virtual switches will become a performance bottleneck for cognitive services without an efficient resource allocation and data scheduling strategy. However, the highly dynamic characteristics of cognitive services make the resource allocation and packet scheduling problem for virtual switches surprisingly challenging. To guarantee the performance of cognitive services, we investigate the joint optimization problem of dynamic resource allocation and packet scheduling for virtual switches. We first model the joint optimization problem of dynamic resource allocation and packet scheduling for virtual switches as a mathematical optimization problem. Then, we analyze the problem with Lyapunov Optimization Framework and derive efficient optimization algorithms with performance tradeoff bounds. At last, we evaluate these algorithms on a testbed and a network-wide simulation platform. Experiment results show that our algorithms outperform other designs and meet the theoretical performance bound.