bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial
Authors:   On behalf of the CRASH-3 trial collaborators, Brenner Amy , Belli Antonio , Chaudhri Rizwana , Coats Timothy , Frimley Lauren , Jamaluddin Sabariah Faizah , Jooma Rashid , Mansukhani Raoul , Sandercock Peter , Shakur-Still Haleema , Shokunbi Temitayo , Roberts Ian 
Published: November 2020

Abstract

Background
The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death.

Methods
The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis.

Results
There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58–0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69–1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83–1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70–0.87) and death within 28 days (RR 0.88, 95% CI 0.82–0.94).

Conclusions
Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury.

Trial registration
ISRCTN15088122, registered on 19 July 2011; NCT01402882, registered on 26 July 2011.
A live-online mindfulness-based intervention for children living with epilepsy and their families: protocol for a randomized controlled trial of Making Mindfulness Matter©
Authors: Puka Klajdi , Bax Karen , Andrade Andrea , Devries-Rizzo Margo , Gangam Hema , Levin Simon , Nouri Maryam N. , Prasad Asuri N. , Secco Mary , Zou Guangyong , Speechley Kathy N. 
Published: November 2020

AbstractBackgroundEpilepsy extends far beyond seizures; up to 80% of children with epilepsy (CWE) may have comorbid cognitive or mental health problems, and up to 50% of parents of CWE are at risk for major depression. Past research has also shown that family environment has a greater influence on children’s and parents’ health-related quality of life (HRQOL) and mental health than epilepsy-related factors. There is a pressing need for low-cost, innovative interventions to improve HRQOL and mental health for CWE and their parents. The aim of this randomized controlled trial (RCT) is to evaluate whether an interactive online mindfulness-based intervention program, Making Mindfulness Matter (M3), can be feasibly implemented and whether it positively affects CWE’s and parents’ HRQOL and mental health (specifically, stress, behavioral, depressive, and anxiety symptoms).MethodsThis parallel RCT was planned to recruit 100 child-parent dyads to be randomized 1:1 to the 8-week intervention or waitlist control and followed over 20 weeks. The intervention, M3, will be delivered online and separately to parents and children (ages 4–10 years) in groups of 4–8 by non-clinician staff of a local community epilepsy agency. The intervention incorporates mindful awareness, social-emotional learning skills, and positive psychology. It is modeled after the validated school-based MindUP program and adapted for provision online and to include a parent component.DiscussionThis RCT will determine whether this online mindfulness-based intervention is feasible and effective for CWE and their parents. The proposed intervention may be an ideal vector to significantly improve HRQOL and mental health for CWE and their parents given its low cost and implementation by community epilepsy agencies.Trial registrationClinicalTrials.govNCT04020484. Registered on July 16, 2019.
Effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine: a single-centre, randomised, double-blind, sham-controlled phase 2 trial (Magnet-EM)
Authors: Mohamad Safiai Nabil Izzaatie , Amir Nur Ain , Basri Hamidon , Inche Mat Liyana Najwa , Hoo Fan Kee , Yusof Khan Abdul Hanif Khan , Loh Wei Chao , Chia Peck Kee , Ramachandran Vasudevan , Mat Din Hazwan , Samsudin Intan Nureslyna , Fernandez Aaron , Mohamed Mohd Hazmi , Ching Siew Mooi , Hashim Hasnur Zaman , Wan Sulaiman Wan Aliaa 
Published: November 2020

AbstractBackgroundThis is a phase II randomised, double-blind, sham-controlled trial to evaluate the effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine amongst migraine subjects.MethodsSubjects age 18 to 60 years will undergo a baseline evaluation to establish the diagnosis of migraine based on the International Classification of Headache Disorder 3rd Edition (ICHD-3). Those who fulfil the ICHD-3 criteria for episodic migraine and compliant to the headache diary during a month run-in period will be enrolled. A total of 76 subjects will be randomised to receive either transcranial magnetic stimulation or sham stimulation for 5 sessions within 2 weeks duration. Follow-up sessions will be conducted monthly for three consecutive months. Prior to treatment, subjects will be required to fill up questionnaires and undergo few procedures such as electroencephalography, transcranial Doppler ultrasound and biochemical analysis for serum serotonin, serum calcitonin gene-related peptide and serum beta-endorphin. These procedures will be repeated at month 3 after receiving the last treatment. The primary outcome measure of this study is the difference in mean monthly migraine days at baseline and at months 1, 2 and 3 after treatment sessions.DiscussionFollowing evidence from previous studies showing restoration of dorsolateral prefrontal cortex (DLPFC) activation to almost normal level, the rTMS intervention will target left DLPFC in this study. An intermediate duration of treatment sessions is selected for this study. It is set to five treatment sessions given within 2 weeks duration.Trial registrationClinicalTrials.govNCT03556722. Registered on 14 June 2018
Local persistence of novel regional variants of La Crosse virus in the Northeast USA
Authors: Eastwood Gillian , Shepard John J. , Misencik Michael J. , Andreadis Theodore G. , Armstrong Philip M. 
Published: November 2020

Abstract
Background
La Crosse virus (LACV) (genus Orthobunyavirus, family Peribunyaviridae) is a mosquito-borne virus that causes pediatric encephalitis and accounts for 50–150 human cases annually in the USA. Human cases occur primarily in the Midwest and Appalachian regions whereas documented human cases occur very rarely in the northeastern USA.

Methods
Following detection of a LACV isolate from a field-collected mosquito in Connecticut during 2005, we evaluated the prevalence of LACV infection in local mosquito populations and genetically characterized virus isolates to determine whether the virus is maintained focally in this region.

Results
During 2018, we detected LACV in multiple species of mosquitoes, including those not previously associated with the virus. We also evaluated the phylogenetic relationship of LACV strains isolated from 2005–2018 in Connecticut and found that they formed a genetically homogeneous clade that was most similar to strains from New York State.

Conclusion
Our analysis argues for local isolation and long-term persistence of a genetically distinct lineage of LACV within this region. We highlight the need to determine more about the phenotypic behavior of these isolates, and whether this virus lineage poses a threat to public health.
Probiotics supplementation and insulin resistance: a systematic review
Authors: Salles Bárbara Izabel Moraes , Cioffi Débora , Ferreira Sandra Roberta G. 
Published: November 2020

Abstract

Background
Research on intestinal microbiota has grown considerably, as well as the interest on probiotics’ supplementation effects on metabolism. Considering high prevalence rates of metabolic diseases linked by insulin resistance, we performed a systematic review of existing literature which addressed the role of probiotics in modulating insulin sensitivity in animals and humans.

Methods
This systematic review was based on PRISMA guidelines. Searches for original articles published in English from 1990 to January 2020 were made in the electronic database of PubMed from the National Library of Medicine, using Medical Subject Headings to identify longitudinal studies conducted in animals and humans which reported effects of probiotics in a variety of insulin resistance parameters.

Results
Overall, results from 27 probiotic interventions (Lactobacillus, Bifidobacterium, Clostridium and Akkermansia) indicated significant beneficial changes in insulin resistance measures in animal studies. Additionally, they improved lipid profile, inflammatory and oxidative markers, short-chain fatty acids production and microbiota composition. In seven clinical trials, samples and designs were heterogeneous. Five showed benefits in insulin resistance parameters and in two others no effect was detected.

Conclusion
Available data regarding the effects of certain probiotics do not guarantee sustained amelioration of insulin resistance in humans. Consistent beneficial results for intestinal barrier function, immune system and metabolism were reported in animals may encourage long-term randomized clinical trials in people with obesity and cardiometabolic risk. Whether supplementation with probiotics in combination with medications and/or prebiotics, associated with a healthy lifestyle, will prove useful to attenuate insulin resistance requires further investigation.
Hemophagocytic lymphohistiocytosis and miliary tuberculosis in a previously healthy individual: a case report
Authors: Trovik Linn Hereide , Sandnes Miriam , Blomberg Bjørn , Holmaas Gunhild , Ahmed Aymen Bushra , Tvedt Tor Henrik Anderson , Vintermyr Olav , Reikvam Håkon 
Published: November 2020

Abstract

Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare heterogenous genetic or acquired hyperinflammatory syndrome associated with a high degree of morbidity and mortality. HLH has clinical manifestations related to abnormal prolonged activation of T lymphocytes and macrophages with an excess of proinflammatory cytokines. The main causes of secondary HLH are malignancies and infectious diseases.

Case presentation
The patient was a 54-year-old man, originally from Eastern Africa, who had lived in Northern Europe for 30 years. Here we describe the clinical features, laboratory parameters, diagnostic workup, management and outcome data of a previously healthy 54-year-old man diagnosed with HLH secondary to tuberculosis. The patient was initially treated for a community-acquired pneumonia. He developed multiorgan failure with acute respiratory distress syndrome, hypertransaminasemia, and kidney and bone marrow dysfunction. The clinical course together with a simultaneous increase in serum ferritin raised the suspicion of HLH. The patient fulfilled seven out of eight diagnostic criteria for HLH. A thorough diagnostic workup with respect to HLH and a potential underlying disease was initiated. Cultivation of bronchoalveolar lavage fluid, stool and urine, and polymerase chain reaction of epithelioid cell granulomas in the bone marrow were all positive for Mycobacterium tuberculosis. He was treated for both HLH and tuberculosis, and he survived without any sequelae.

Conclusions
We present one of few published cases of a patient who survived HLH triggered by miliary tuberculosis. The current case illustrates the need for awareness of these two diagnoses, and the timely initiation of specific and supportive treatment to reduce mortality.
Adipose-derived stromal cells modulating composite allotransplant survival is correlated with B cell regulation in a rodent hind-limb allotransplantation model
Authors: Chen Chien-Chang , Chen Rong-Fu , Shao Jheng-Syuan , Li Yun-Ting , Wang Yu-Chi , Brandacher Gerald , Chuang Jiin-Haur , Kuo Yur-Ren 
Published: November 2020

Abstract

Background
Our previous studies demonstrated that adipose-derived mesenchymal stromal cells (ASCs) have immunomodulatory effects that prolong allograft survival in a rodent hind-limb allotransplant model. In this study, we investigated whether the effects of immunomodulation by ASCs on allograft survival are correlated with B cell regulation.

Methods
B cells isolated from splenocytes were cocultured with ASCs harvested from adipose tissue from rodent groin areas for in vitro experiments. In an in vivo study, hind-limb allotransplantation from Brown-Norway to Lewis rats was performed, and rats were treated with ASCs combined with short-term treatment with anti-lymphocyte serum (ALS)/cyclosporine (CsA) as immunosuppressants. Peripheral blood and transplanted tissue were collected for further analysis.

Result
An in vitro study revealed that ASCs significantly suppressed lipopolysaccharide-activated B cell proliferation and increased the percentage of Bregs. The levels of immunoregulatory cytokines, such as TGF-β1 and IL-10, were significantly increased in supernatants of stimulated B cells cocultured with ASCs. The in vivo study showed that treatment with ASCs combined with short-term ALS/CsA significantly reduced the B cell population in alloskin tissue, increased the proportion of circulating CD45Ra+/Foxp3+ B cells, and decreased C4d expression in alloskin.

Conclusion
ASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines.
Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head
Authors: Li Lu , Wang Yikai , Yu Xiaobing , Bao Yongming , An Lijia , Wei Xiaowei , Yu Weiting , Liu Baoyi , Li Junlei , Yang Jiahui , Xia Yan , Liu Ge , Cao Fang , Zhang Xiuzhi , Zhao Dewei 
Published: November 2020

Abstract

Background
Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH.

Methods
To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes.

Results
The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1.

Conclusions
This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.
LigGrep: a tool for filtering docked poses to improve virtual-screening hit rates
Authors: Ha Emily J. , Lwin Cara T. , Durrant Jacob D. 
Published: November 2020

AbstractStructure-based virtual screening (VS) uses computer docking to prioritize candidate small-molecule ligands for subsequent experimental testing. Docking programs evaluate molecular binding in part by predicting the geometry with which a given compound might bind a target receptor (e.g., the docked “pose” relative to a protein target). Candidate ligands predicted to participate in the same intermolecular interactions typical of known ligands (or ligands that bind related proteins) are arguably more likely to be true binders. Some docking programs allow users to apply constraints during the docking process with the goal of prioritizing these critical interactions. But these programs often have restrictive and/or expensive licenses, and many popular open-source docking programs (e.g., AutoDock Vina) lack this important functionality. We present LigGrep, a free, open-source program that addresses this limitation. As input, LigGrep accepts a protein receptor file, a directory containing many docked-compound files, and a list of user-specified filters describing critical receptor/ligand interactions. LigGrep evaluates each docked pose and outputs the names of the compounds with poses that pass all filters. To demonstrate utility, we show that LigGrep can improve the hit rates of test VS targetingH. sapienspoly(ADPribose) polymerase 1 (HsPARP1),H. sapienspeptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (HsPin1p), andS. cerevisiaehexokinase-2 (ScHxk2p). We hope that LigGrep will be a useful tool for the computational biology community. A copy is available free of charge athttp://durrantlab.com/liggrep/.
On a new structure of the pantograph inclusion problem in the Caputo conformable setting
Authors: Thabet Sabri T. M. , Etemad Sina , Rezapour Shahram 
Published: November 2020

Abstract
In this work, we reformulate and investigate the well-known pantograph differential equation by applying newly-defined conformable operators in both Caputo and Riemann–Liouville settings simultaneously for the first time. In fact, we derive the required existence criteria of solutions corresponding to the inclusion version of the three-point Caputo conformable pantograph BVP subject to Riemann–Liouville conformable integral conditions. To achieve this aim, we establish our main results in some cases including the lower semi-continuous, the upper semi-continuous and the Lipschitz set-valued maps. Eventually, the last part of the present research is devoted to proposing two numerical simulative examples to confirm the consistency of our findings.
New post quantum analogues of Ostrowski-type inequalities using new definitions of left–right $(p,q)$-derivatives and definite integrals
Authors: Chu Yu-Ming , Awan Muhammad Uzair , Talib Sadia , Noor Muhammad Aslam , Noor Khalida Inayat 
Published: November 2020

AbstractThe main objective of this paper is to introduce a new more elegant notion of left–right$(p,q)$(p,q)-derivative and definite integrals. To show the significance of these concepts, we discuss some of their basic properties. A new generalized$(p,q)$(p,q)-integral identity is also obtained. Utilizing this identity as an auxiliary result we then obtain our main results using the concept ofn-polynomial convex functions.
Inflammatory breast cancer associated with amyopathic dermatomyositis: a case report
Authors: Inaguma Gaku , Shimada Akihiko , Tsunoda Junya , Matsuzaki Tomohiko , Nishi Tomohiko , Seki Hiroaki , Matsumoto Hidetoshi 
Published: November 2020

Abstract

Background
Dermatomyositis is associated with malignant tumors including breast cancer, and inflammatory breast cancer is considered to have a poorer prognosis than most breast cancers.

Case presentation
A 74-year-old Asian woman, developed erythema on her face, back, and the back of her hands, 3 weeks before attending our department. At the same time, she had noticed a right breast mass and redness of the skin of the breast. The clinical findings and vacuum aspiration biopsy diagnosed inflammatory breast cancer and neoadjuvant chemotherapy was performed. The mass and enlarged axillary lymph nodes had shrunk, therefore a total mastectomy was performed. The sentinel lymph node biopsy was negative. She was discharged 7 days after surgery without any complications. She has received a postoperative aromatase inhibitor and is alive without recurrence. The dermatomyositis also began to improve with the start of her chemotherapy and has not recurred since the surgery.

Conclusions
Neoadjuvant chemotherapy was performed for inflammatory breast cancer with dermatomyositis, and tumor shrinkage was confirmed. A total mastectomy without axillary lymph node dissection was performed. Dermatomyositis and breast cancer have not recurred. Dermatomyositis may have been a paraneoplastic syndrome due to breast cancer.
The role of clockwork orange in the circadian clock of the cricket Gryllus bimaculatus
Authors: Tomiyama Yasuaki , Shinohara Tsugumichi , Matsuka Mirai , Bando Tetsuya , Mito Taro , Tomioka Kenji 
Published: November 2020

Abstract
The circadian clock generates rhythms of approximately 24 h through periodic expression of the clock genes. In insects, the major clock genes period (per) and timeless (tim) are rhythmically expressed upon their transactivation by CLOCK/CYCLE, with peak levels in the early night. In Drosophila, clockwork orange (cwo) is known to inhibit the transcription of per and tim during the daytime to enhance the amplitude of the rhythm, but its function in other insects is largely unknown. In this study, we investigated the role of cwo in the clock mechanism of the cricket Gryllus bimaculatus. The results of quantitative RT-PCR showed that under a light/dark (LD) cycle, cwo is rhythmically expressed in the optic lobe (lamina-medulla complex) and peaks during the night. When cwo was knocked down via RNA interference (RNAi), some crickets lost their locomotor rhythm, while others maintained a rhythm but exhibited a longer free-running period under constant darkness (DD). In cwoRNAi crickets, all clock genes except for cryptochrome 2 (cry2) showed arrhythmic expression under DD; under LD, some of the clock genes showed higher mRNA levels, and tim showed rhythmic expression with a delayed phase. Based on these results, we propose that cwo plays an important role in the cricket circadian clock.