bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and comparison of novel circular RNAs with associated co-expression and competing endogenous RNA networks in postmenopausal osteoporosis
Authors: Diao Weiyi , Wang Yongguang , Zhang Jun , Shao Haiyu , Huang Yazeng , Jin Mengran 
Published: July 2021

Abstract
Background
Circular RNAs (circRNAs) are emerging as crucial regulators in various human diseases. So far, the expression profile and regulatory mechanism of circRNAs in postmenopausal osteoporosis (PMOP) are less studied and should be deciphered urgently. Herein, we aimed to reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions.

Methods
To reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions, whole transcriptome sequencing and bioinformatics analysis were performed to identify differentially expressed circRNAs (DECs). The expression pattern and regulatory networks of DECs in peripheral blood mononuclear cells (PBMCs) were unearthed.

Results
A total of 373 DECs comprising 123 intronic, 100 antisense, 70 exonic, 55 intergenic, and 25 sense-overlapping circRNAs were identified. Among these, 73 circRNAs were upregulated and 300 were downregulated. These DECs exerted pivotal functions in the pathogenesis of PMOP as demonstrated by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The circRNA-miRNA-mRNA co-expression network comprising 28 DECs, 145 miRNAs, and 175 differentially expressed mRNAs predicted the possible mechanism of the pathogenesis and progression of PMOP.

Conclusion
The results of the present study provided a further comprehension of circRNA-associated competing endogenous RNA regulatory mechanism in PMOP. The steadily expressed and disease-specific DECs may serve as promising diagnostic and prognostic biomarkers for PMOP.
Neutrophil Extracellular Traps: A New Player in Cancer Metastasis and Therapeutic Target
Authors: Yang Dakai , Liu Jing 
Published: July 2021

AbstractNeutrophil Extracellular Traps (NETs) are neutrophil-derived extracellular scaffolds, which typically consist of fibrous decondensed chromatins decorated with histones and granule proteins. Initially discovered as a host defence mechanism of neutrophil against pathogens, they have also been implicated in the progression of sterile inflammation-associated diseases such as autoimmune disease, diabetes, and cancer. In this review, we highlight and discuss the more recent studies on the roles of NETs in cancer development, with a special focus on cancer metastasis. Moreover, we present the strategies for targeting NETs in pre-clinical models, but also the challenging questions that need to be answered in the field.
The genetic architecture of temperature adaptation is shaped by population ancestry and not by selection regime
Authors: Otte Kathrin A. , Nolte Viola , Mallard François , Schlötterer Christian 
Published: July 2021

AbstractBackgroundUnderstanding the genetic architecture of temperature adaptation is key for characterizing and predicting the effect of climate change on natural populations. One particularly promising approach is Evolve and Resequence, which combines advantages of experimental evolution such as time series, replicate populations, and controlled environmental conditions, with whole genome sequencing. Recent analysis of replicate populations from two differentDrosophila simulansfounder populations, which were adapting to the same novel hot environment, uncovered very different architectures—either many selection targets with large heterogeneity among replicates or fewer selection targets with a consistent response among replicates.ResultsHere, we expose the founder population from Portugal to a cold temperature regime. Although almost no selection targets are shared between the hot and cold selection regime, the adaptive architecture was similar. We identify a moderate number of targets under strong selection (19 selection targets, mean selection coefficient = 0.072) and parallel responses in the cold evolved replicates. This similarity across different environments indicates that the adaptive architecture depends more on the ancestry of the founder population than the specific selection regime.ConclusionsThese observations will have broad implications for the correct interpretation of the genomic responses to a changing climate in natural populations.
An Internet-based emotion regulation intervention versus no intervention for non-suicidal self-injury in adolescents: a statistical analysis plan for a feasibility randomised clinical trial
Authors: Olsen Markus Harboe , Morthorst Britt , Pagsberg Anne Katrine , Heinrichsen Michella , Møhl Bo , Rubæk Lotte , Bjureberg Johan , Simonsson Olivia , Lindschou Jane , Gluud Christian , Jakobsen Janus Christian 
Published: July 2021

Abstract
Background
Non-suicidal self-injury (NSSI) has a lifetime prevalence of 17% in adolescents in the general population and up to 74% in adolescents with psychiatric disorders. NSSI is one of the most important predictors of later suicidal behaviour and death by suicide. The TEENS feasibility trial was initiated to assess the feasibility and safety of Internet-based Emotion Regulation Individual Therapy for Adolescents (ERITA) as an add-on to treatment as usual in 13–17-year-old patients with NSSI referred to the Child and Adolescent Mental Health Services.

Methods
The TEENS feasibility trial is a randomised clinical trial with a parallel-group design. The trial intervention is an 11-week online therapy which is tested as an add-on to treatment as usual versus treatment as usual. The primary feasibility outcomes are the fraction of participants who (1) completed 12 weeks of follow-up interview or assessment, (2) consented to inclusion and randomisation out of all eligible participants, and (3) were compliant with the experimental intervention, assessed as completion of at least six out of eleven modules in the programme. Since this is a feasibility trial, we did not predefine a required sample size. The exploratory clinical outcome, the frequency of NSSI episodes, assessed using Deliberate Self-Harm Inventory – Youth version (DSHI-Y), at the end of intervention, is planned to be the future primary outcome in a larger pragmatic definitive randomised clinical trial. After completion of the feasibility trial, blinded data will be analysed by two independent statisticians blinded to the intervention, where ‘A’ and ‘B’ refer to the two groups. A third party will compare these reports, and discrepancies will be discussed. The statistical report with the analyses chosen for the manuscript is being tracked using a version control system, and both statistical reports will be published as a supplementary material. Based on the final statistical report, two blinded conclusions will be drawn by the steering group.

Discussion
We present a pre-defined statistical analysis plan for the TEENS feasibility trial, which limits bias, p-hacking, data-driven interpretations. This statistical analysis plan is accompanied by a pre-programmed version-controlled statistical report with simulated data, which increases transparency and reproducibility.

Trial registration
ClinicalTrials.govNCT04243603. Registered on 28 January 2020
Moderate-intensity exercise versus high-intensity interval training to recover walking post-stroke: protocol for a randomized controlled trial
Authors: Miller Allison , Reisman Darcy S. , Billinger Sandra A. , Dunning Kari , Doren Sarah , Ward Jaimie , Wright Henry , Wagner Erin , Carl Daniel , Gerson Myron , Awosika Oluwole , Khoury Jane , Kissela Brett , Boyne Pierce 
Published: July 2021

AbstractBackgroundStroke results in neurologic impairments and aerobic deconditioning that contribute to limited walking capacity which is a major barrier post-stroke. Current exercise recommendations and stroke rehabilitation guidelines recommend moderate-intensity aerobic training post-stroke. Locomotor high-intensity interval training is a promising new strategy that has shown significantly greater improvements in aerobic fitness and motor performance than moderate-intensity aerobic training in other populations. However, the relative benefits and risks of high-intensity interval training and moderate-intensity aerobic training remain poorly understood following stroke. In this study, we hypothesize that locomotor high-intensity interval training will result in greater improvements in walking capacity than moderate-intensity aerobic training.MethodsUsing a single-blind, 3-site randomized controlled trial, 50 chronic (> 6 months) stroke survivors are randomly assigned to complete 36 locomotor training sessions of either high-intensity interval training or moderate-intensity aerobic training. Main eligibility criteria are age 40–80 years, single stroke for which the participant received treatment (experienced 6 months to 5 years prior to consent), walking speed ≤ 1.0 m/s, able to walk at least 3 min on the treadmill at ≥ 0.13 m/s (0.3 mph), stable cardiovascular condition (American Heart Association class B), and the ability to walk 10 m overground without continuous physical assistance. The primary outcome (walking capacity) and secondary outcomes (self-selected and fast gait speed, aerobic fitness, and fatigue) are assessed prior to initiating training and after 4 weeks, 8 weeks, and 12 weeks of training.DiscussionThis study will provide fundamental new knowledge to inform the selection of intensity and duration dosing parameters for gait recovery and optimization of aerobic training interventions in chronic stroke. Data needed to justify and design a subsequent definitive trial will also be obtained. Thus, the results of this study will inform future stroke rehabilitation guidelines on how to optimally improve walking capacity following stroke.Trial registrationClinicalTrials.govNCT03760016. Registered on November 30, 2018.
Stakeholder perspectives on barriers and enablers to recruiting anxious children undergoing day surgery under general anaesthetic: a qualitative internal pilot study of the MAGIC randomised controlled trial
Authors: Kettle Jennifer , Deery Chris , Bolt Robert , Papaioannou Diana , Marshman Zoe 
Published: July 2021

Abstract

Background
The ‘Melatonin for Anxiety prior to General anaesthesia In Children’ (MAGIC) trial was designed to compare midazolam and melatonin as pre-medications for anxious children (aged five to fourteen), undergoing day-case surgical procedures under general anaesthesia. Low recruitment is a challenge for many trials, particularly paediatric trials and those in ‘emergency’ settings. A qualitative study as part of MAGIC aimed to gather stakeholder perspectives on barriers and enablers to recruitment.

Methods
Sixteen stakeholders from six sites participated in semi-structured interviews about their experiences of setting up the MAGIC trial and recruiting patients as part of the internal pilot. Data was analysed using framework analysis.

Results
Participants identified barriers and enablers to recruitment. Barriers and enablers related to the study, participants, the population of anxious children, practitioners, collaboration with other health professionals, ethics, specific settings and the context of surgical day units and the wider health system. Attempting to recruit anxious children from a surgical day unit is particularly challenging for several reasons. Issues include the practicalities of dealing with a child experiencing anxiety for parents/guardians; professional unwillingness to make things more difficult for families and clinicians and nurses valuing predictability within a busy and time-sensitive setting.

Conclusions
Multi-site RCTs face recruitment barriers relating to study-wide and site-specific factors. There are multiple barriers to recruiting anxious children due to undergo day-case surgery. Barriers across domains can interrelate and reinforce each other, reflecting challenges relating to populations and settings. For example, in the case of anxious children, parents and other health professionals are concerned about exacerbating children’s anxiety prior to surgery. They may look for ways to keep things predictable and avoid the uncertainty of an RCT. Pre-trial engagement work could help address concerns among collaborating health professionals.
Using rapid ethnography during set-up or an internal pilot to focus on how the protocol will be or has been operationalised in practice may help identify issues. Allowing time to reflect on the findings of internal pilots and implement necessary changes could facilitate higher recruitment during the main phase of a trial.

Trial registration
NIHR Trial Registration Number: ISRCTN18296119. Registered on October 01, 2019.
Effects of a low-dose IL-2 treatment in HLA-B27 transgenic rat model of spondyloarthritis
Authors: Araujo L. M. , Jouhault Q. , Fert I. , Bouiller I. , Chiocchia G. , Breban M. 
Published: July 2021

Abstract

Introduction/Aim
HLA-B27/human β2m transgenic rats (B27-rats) develop an inflammatory disorder resembling spondyloarthritis (SpA) with dysregulated IL-10/IL-17 production by regulatory T cells (Treg). Treg plays a major role in controlling pathogenic inflammatory processes. Interleukin 2 (IL-2), a cytokine which promotes Treg cell survival and function, may thus have therapeutic efficacy in SpA. Here, we tested this hypothesis using a low dose of IL-2 treatment in B27-rat.

Material and methods
B27-rats aged 4 weeks (before disease onset) and nontransgenic (NTG) littermates were administered intraperitoneally recombinant human IL-2 (Sanofi®; 2,000IU/injection) or PBS, 3 days per week during 6 weeks. Assessment of treatment effect was performed, based on clinical (weight, diarrhea, arthritis), histological (proximal and distal colon, caecum, ileum and tarsal/ankle joint) scores, and frequency of Treg in the spleen and lymph nodes (LN).

Results
IL-2 administration had no effect on weight gain, either in B27- or NTG-rats. Over the 6 weeks of treatment, the clinical disease score worsened similarly in both IL-2-treated and control groups of B27-rats. The macroscopic and histological evaluation of gut and joints showed marked inflammation in B27-rats; however, no change related to IL-2 treatment was observed. In the B27-rats, the percentage of Treg was moderately increased after IL-2 treatment in the spleen, but neither in mesenteric nor peripheral LN in those rats.

Conclusion
Our data demonstrate that a low dose of IL-2 administered before disease onset was moderately effective for boosting Treg but failed to prevent SpA development in B27-rat.
Severe acute respiratory syndrome coronavirus 2 reinfection in a coronavirus disease 2019 recovered young adult: a case report
Authors: Awada Hussein , Nassereldine Hasan , Hajj Ali Adel 
Published: July 2021

AbstractBackgroundCoronavirus disease 2019 has been a public health threat and a worldwide emergency for more than a year. Unfortunately, many questions concerning the pathophysiology, management, and long-term side effects remain unanswered, and novel aspects of the disease keep on emerging. Of concern to healthcare providers are the recent reported cases of reinfection. Serum coronavirus disease 2019 antibodies have been detected within a few days after onset of the disease. However, it remains unclear whether this immune response is universal, or whether it can lead to latent immunity.Case presentationA previously healthy 27-year-old white man presented with fever, chills, back pain, and other constitutional symptoms, 2 days after being exposed to coronavirus disease 2019 positive patients. His severe acute respiratory syndrome coronavirus 2 polymerase chain reaction was positive, and his symptoms resolved over the next 2 weeks. One month after a confirmatory negative severe acute respiratory syndrome coronavirus 2 polymerase chain reaction, he was found to be ineligible for plasma donation as his anti-severe acute respiratory syndrome coronavirus 2 serology was negative. The patient redeveloped symptoms similar to his first infection 3 weeks after the negative serology test. He and his wife both tested positive via polymerase chain reaction. Their symptoms resolved over the next few days, and they had a negative polymerase chain reaction test 10 days after the positive polymerase chain reaction.ConclusionWhile studies showed that anti-severe acute respiratory syndrome coronavirus 2 immunoglobulins start to develop early after infection, our healthy young patient’s immune system failed to mount latent immunity against the virus. This left him, especially amid widespread social and medical misconceptions, vulnerable to reinfection by severe acute respiratory syndrome coronavirus 2. Our case disputes the timelines for immune response that were set and supported by research studies. Our case also raises questions regarding prioritizing vaccinating other individuals over those with prior infection.
Identification and characterization of miRNAs associated with sterile flower buds in the tea plant based on small RNA sequencing
Authors: Qu Hao , Liu Yue , Jiang Huibing , Liu Yufei , Song Weixi , Chen Linbo 
Published: July 2021

Abstract
Background
miRNAs are a type of conserved, small RNA molecule that regulate gene expression and play an important role in the growth and development of plants. miRNAs are involved in seed germination, root development, shoot apical meristem maintenance, leaf development, and flower development by regulating various target genes. However, the role of miRNAs in the mechanism of tea plant flower sterility remains unclear. Therefore, we performed miRNA sequencing on the flowers of fertile male parents, female parents, and sterile offspring.

Results
A total of 55 known miRNAs and 90 unknown miRNAs were identified. In the infertile progeny, 37 miRNAs were differentially expressed; 18 were up-regulated and 19 were down-regulated. miR156, miR157, miR164, miR167, miR169, miR2111 and miR396 family members were down-regulated, and miR160, miR172 and miR319 family members were up-regulated. Moreover, we predicted that the 37 differentially expressed miRNAs target a total of 363 genes, which were enriched in 31 biological functions. We predicted that miR156 targets 142 genes, including ATD1A, SPL, ACA1, ACA2, CKB22 and MADS2.

Conclusion
We detected a large number of differentially expressed miRNAs in the sterile tea plant flowers, and their target genes were involved in complex biological processes. Among these miRNAs, the down-regulation of miR156 may be one of the factor in the formation of sterile floral buds in tea plants.
Vertebral Fractures Occur Despite Control of Acromegaly and Are Predicted by Cortical Volumetric Bone Mineral Density
Authors: Kužma Martin , Vaňuga Peter , Ságová Ivana , Pávai Dušan , Jackuliak Peter , Killinger Zdenko , Binkley Neil , Winzenrieth Renaud , Payer Juraj 
Published: July 2021

Abstract

Context
Recent studies suggest that cortical bone could also play a role in vertebral fracture (VF) development in acromegaly.

Objective
Evaluate the occurrence of VFs and their relationship to dual energy x-ray absorptiometry–derived bone parameters.

Methods
A single-center 2-year prospective study of acromegaly patients was conducted. Each subject had L1-4 spine, femoral neck and total hip (TH) areal BMD measured using DXA, and trabecular bone score (TBS) measurement performed. 3D Shaper™ was used to assess proximal femur trabecular and cortical volumetric (v)BMD, cortical surface (s)BMD, and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using a semiquantitative approach. Study outcomes were assessed at 2 time points: baseline and month 24.

Results
70 acromegaly patients (34 M/36F; average 55.1 years) were studied, including 26 with active disease. In 13 patients, 9 with controlled disease, VF was observed. A decrease in TBS, sBMD, neck trabecular vBMD, TH, and neck cortical vBMD in VF compared with non-VF subjects was observed (P &lt; .05). Multivariate analysis of fracture prediction showed TH cortical vBMD as the best fracture prediction parameter with area under the curve of 0.774. TBS was negatively associated with fasting plasma glucose and glycated hemoglobin (HBA1c) at each time point during the follow-up.

Conclusion
From the total number of 13 VF subjects, 9 were in the controlled disease group. The most sensitive and specific predictor of incident VF was TH cortical vBMD, suggesting that cortical bone is involved in fracture development.
Clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins and preimplantation development
Authors: Morita Akihito , Satouh Yuhkoh , Kosako Hidetaka , Kobayashi Hisae , Iwase Akira , Sato Ken 
Published: July 2021

ABSTRACT
Fertilization triggers significant cellular remodeling through the oocyte-to-embryo transition. In this transition, the ubiquitin-proteasome system and autophagy are essential for the degradation of maternal components; however, the significance of degradation of cell surface components remains unknown. In this study, we show that multiple maternal plasma membrane proteins, such as the glycine transporter GlyT1a, are selectively internalized from the plasma membrane to endosomes in mouse embryos by the late two-cell stage and then transported to lysosomes for degradation at the later stages. During this process, large amounts of ubiquitylated proteins accumulated on endosomes. Furthermore, the degradation of GlyT1a with mutations in potential ubiquitylation sites was delayed, suggesting that ubiquitylation may be involved in GlyT1a degradation. The clathrin inhibitor blocked GlyT1a internalization. Strikingly, the protein kinase C (PKC) activator triggered the heterochronic internalization of GlyT1a; the PKC inhibitor markedly blocked GlyT1a endocytosis. Lastly, clathrin inhibition completely blocked embryogenesis at the two-cell stage and inhibited cell division after the four-cell stage. These findings demonstrate that PKC-dependent clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins during oocyte-to-embryo transition and early embryogenesis.
Radical Hemiscrotectomy and En Bloc Orchidectomy: Surgical Technique and Perioperative and Oncologic Outcomes of a Supra-Regional UK Referral Centre
Authors: Fankhauser Christian Daniel , Issa Allaudin , Lee Esther W. C. , Oing Christoph , Oliveira Pedro , Parnham Arie , Oates Jeremy , Sangar Vijay , Gulamhusein Aziz , Clarke Noel 
Published: July 2021

Abstract
Background and Purpose
Hemiscrotectomy with en bloc orchidectomy represents a radical primary, completion, or salvage option in men with inguinoscrotal cancers. We describe our surgical technique and peri-operative and oncological outcomes.

Patients and Methods
Retrospective cohort study of 16 men treated at a supra-regional referral centre with open radical hemiscrotectomy with or without en bloc orchidectomy between 2010 and 2020. Peri-operative and survival outcomes were analysed.

Results
Radical hemiscrotectomy with or without en bloc orchidectomy was performed on 16 patients comprising 7 well-differentiated liposarcomas, 4 dedifferentiated liposarcomas, 2 leiomyosarcomas, 1 mesothelioma, 1 rhabdomyosarcoma and 1 mammary type myofibroblastoma. Primary hemiscrotectomy was performed in four, completion hemiscrotectomy in nine and salvage hemiscrotectomy in three. The median hospital stay was 2 days [interquartile range (IQR) 2–4]. Four patients (25%) had post-operative complications including wound infection or haematoma. During a median follow-up of 18 months (IQR 2–66), one patient (6%) died following a recurrence in the pelvis and retroperitoneum.

Discussion
and Conclusions
If careful dissection is performed, radical hemiscrotectomy and en bloc orchidectomy is a radical but safe procedure with a short hospital stay. Haematoma and infection represent the main complications, and within limited follow-up most men showed no recurrence.