bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mir-30B-5P Inhibits Proliferation and Promotes Apoptosis of Medulloblastoma Cells via Targeting Myb Proto-Oncogene like 2 (Mybl2)
Authors: Xu Chengyan , He Zixia , Lin Chao , Shen Zhipeng 
Published: July 2020

Medulloblastoma (MB) is the most common malignant brain tumors among children. MiR-30b-5p is a potential tumor suppressor in a variety of human cancers. However, its expression and function in MB remain poorly understood. This study aimed to investigate the expression, role and regulatory mechanism of miR-30b-5p in MB. The expression of miR-30b-5p in MB tissues and cell lines was detected by real-time PCR. The effects of miR-30b-5p on cell proliferation and apoptosis were monitored by CCK-8 (Cell Counting Kit-8) assay, colony formation assay and flow cytometry, respectively. Bioinformatics database TargetScan predicted the target genes of miR-30b-5p. The interaction between miR-30b-5p and MYB proto-oncogene Like 2 (MYBL2) was determined by luciferase reporter gene assay. We demonstrated that the expression of miR-30b-5p was significantly downregulated in MB. Upregulated miR-30b-5p could inhibit the proliferation and induce apoptosis of MB. Moreover, overexpressed miR-30b-5p could increase the expression of BAX but decrease that of Bcl-2. Downregulated miR-30b-5p exerted the opposite effect. MYBL2 was proved to be the target gene of miR-30b-5p and was negatively regulated by miR-30b-5p. These results indicate that miR-30b-5p inhibits the progression of MB via targeting the expression of MYBL2.
Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke
Authors: Al Saiegh Fadi , Ghosh Ritam , Leibold Adam , Avery Michael B , Schmidt Richard F , Theofanis Thana , Mouchtouris Nikolaos , Philipp Lucas , Peiper Stephen C , Wang Zi-Xuan , Rincon Fred , Tjoumakaris Stavropoula I , Jabbour Pascal , Rosenwasser Robert H , Gooch M. Reid 
Published: July 2020

BackgroundEmergence of the novel corona virus (severe acute respiratory syndrome (SARS)-CoV-2) in December 2019 has led to the COVID-19 pandemic. The extent of COVID-19 involvement in the central nervous system is not well established, and the presence or the absence of SARS-CoV-2 particles in the cerebrospinal fluid (CSF) is a topic of debate.Case descriptionWe present two patients with COVID-19 and concurrent neurological symptoms. Our first patient is a 31-year-old man who had flu-like symptoms due to COVID-19 and later developed an acute-onset severe headache and loss of consciousness and was diagnosed with a Hunt and Hess grade 3 subarachnoid haemorrhage from a ruptured aneurysm. Our second patient is a 62-year-old woman who had an ischaemic stroke with massive haemorrhagic conversion requiring a decompressive hemicraniectomy. Both patients’ CSF was repeatedly negative on real-time PCR analysis despite concurrent neurological disease.ConclusionOur report shows that patients’ CSF may be devoid of viral particles even when they test positive for COVID-19 on a nasal swab. Whether SARS-CoV-2 is present in CSF may depend on the systemic disease severity and the degree of the virus’ nervous tissue tropism and should be examined in future studies.
3 The dopaminergic balancing act: a literature review of a novel COMT inhibitor opicapone with a focus on the risk of visual hallucinations
Authors: Cole Richard , Saha Romi 
Published: July 2020

AimsParkinson’s Disease (PD) medications are well-evidenced for improving motor symptoms. However, often a balancing act is required to ameliorate positive neuropsychiatric symptoms, such as visual hallucinations (VH). Opicapone, a novel COMT inhibitor, has been shown by BIPARK-1 and BIPARK-2 studies to improve wearing-off phenomena but little is known about associated neuropsychiatric symptoms. The aim of this literature review was to investigate any association between opicapone and VH.MethodsA literature review was undertaken on the 18th July 2019 using PubMed, Ovid (using key resources of Embase, Ovid MEDLINE, Global Health and PsycINFO), Web of Science and Scopus. The search terms used were ‘Parkinson’s Disease’ and ‘Opicapone’. The search included full-texts, abstracts, conference abstracts and posters.ResultsThe initial search produced 398 articles; 391 were excluded. Of the 7 articles reviewed there were two randomised controlled trials (RCTs) (BIPARK-1 and -2), two observational studies, two post-hoc analyses of BIPARK-1 and -2, and one retrospective analysis. BIPARK-1 reported VH in 1% of the entacapone group, 8% opicapone 25 mg group and 4% of the opicapone 50 mg group. BIPARK-2 did not report on VH in their randomised phased and reported VH in 0.8% of opicapone patients in their open-label phase but without specifying the associated dose.Chaudhuri et al.’s (2018) post-hoc analysis of BIPARK-1 reported VH in 8% of COMT- naive patients given opicapone, vs. 1% of those given entacapone. Lees et al.’s (2019) post-hoc analysis of BIPARK-1 & -2 reported VH in 4.6% of patients receiving opicapone who were ≥70 years old, vs 0.6% in those younger. Gandor et al.’s (2018) prospective observational study reported VH in 14.8% of patients given opicapone.ConclusionsSeveral factors limit the conclusions drawn about the risk of VH in patients taking opicapone. The RCTs were designed and powered to assess ‘on-off’ phenomena and didn’t include patients >65 or with a psychiatric history. This also limits their post-hoc analyses’ generalisability. The more ‘real-world’ observational studies were small and only available in abstract form with limited details. Lees et al.’s (2019) post-hoc analysis nevertheless reported a higher incidence of VH in the older age group, which is concordant with known risk factors for neuropsychiatric adverse events. Further investigation is required, focusing on older patients and those with a psychiatric history or cognitive impairment.
8 Functional neurological disorder (FND) patients’ experience of healthcare interventions
Authors: Symeon C , Isaacs-Itua A , Saramandi A 
Published: July 2020

ObjectivesDespite Functional Neurological Disorder (FND) accounting for approximately 25% of Neurology out-patient appointments, and being frequently comorbid with other neurological conditions, there are only 4 centres in the UK, offering in-patient treatment programmes. Subsequently, services are strained as patients face long waiting lists and likely deterioration of symptoms. We explored patients’ experience of this and the impact on their wellbeing.MethodsAn on-line survey was sent to patients with a diagnosis of FND, who had, at out- patient assessment been deemed appropriate candidates for in-patient rehabilitation, and had provided written consent to be included in research. The survey question themes included: demography, understanding of FND diagnosis, subjective opinion of symptom progression, use of primary care services and/or Emergency Departments, and access to support and employment opportunities.Response where subjective opinion was sought, e.g. understanding of diagnosis, was via Likert scale ratings (from 0 (no understanding at all) to 10 (full understanding). All responses were anonymous.Results12 patients completed the survey (n=12). Of these, 7 were female and 5, male. 11 patients were aged between 25–64 years and 1, aged over 65 years. More than half of patients had seen their GP or visited an Emergency Department with symptoms related to FND in the past year. Average understanding of FND diagnosis was rated as 6.5, of treatment options as 4.8 and confidence of the likelihood of full recovery as 3.5 (on a scale of 0–10). 7 patients had carers, of whom the majority were family members. 9 patients would consider the use of digital interventions or day therapy programmes and 10 patients had already completed an in-patient rehabilitation programme. Of these, 9 had been on the in-patient waiting list for over 6 months. 8 patients felt that their symptoms had deteriorated and 6 patients described their level of independence, as being ‘much worse’, while on the waiting list.ConclusionsWhile we appreciate that this is a small sample size, it does offer invaluable insight into the experiences of those with FND, particularly with regards to healthcare intervention. Patients with FND inevitably use what would be regarded as high levels of healthcare intervention, although this must be considered within the context of limited healthcare resources available to them.
Heart team approach in treatment of mitral regurgitation: patient selection and outcome
Authors: Külling Mischa , Corti Roberto , Noll Georg , Küest Silke , Hürlimann David , Wyss Christophe , Reho Ivano , Tanner Felix C , Külling Jeremy , Meinshausen Nicolai , Gaemperli Oliver , Wenaweser Peter , Salzberg Sacha P , Aymard Thierry , Grünenfelder Jürg , Biaggi Patric 
Published: July 2020

ObjectiveA multidisciplinary heart valve team is recommended for the evaluation of treatment in patients with valvular heart disease, but evidence supporting this concept is lacking. In patients with severe mitral regurgitation, we thought to analyse the patient selection process by the heart team for different treatment options and the outcome after treatment.MethodsIn this single-centre cohort study, all patients treated for mitral regurgitation between July 2013 and September 2018 were included. Primary end points during follow-up were all-cause mortality and a combined end point, consisting of all-cause mortality, cardiovascular rehospitalisation and mitral valve reintervention.Results179 patients (44.8%) were treated using Mitraclip, 185 (46.2%) by surgical repair and 36 (9.0%) by surgical replacement. The mortality risk according to EuroScore II differed significantly between treatment groups (6.6%±5.6%, 1.7%±1.5% and 3.6%±2.7% for Mitraclip, surgical repair and replacement, respectively, p<0.001). In-hospital mortality for the 3 groups were 3.4%, 1.6% and 8.3%, respectively (p=0.091). Overall, surgical repair patients had higher 4-year survival (HR 0.40 (95% CI 0.26 to 0.63), p<0.001) and fewer combined end points (HR 0.51 (95% CI 0.32 to 0.80), p<0.001) compared with surgical replacement and Mitraclip patients. However, patients undergoing Mitraclip for isolated, primary mitral regurgitation achieved very good long-term survival.ConclusionThe multidisciplinary heart team assigned only low-risk patients with favourable anatomy to surgical repair, while high-risk patients underwent Mitraclip or surgical replacement. This strategy was associated with lower than expected in-hospital mortality for Mitraclip patients and high 4-year survival rates for patients undergoing surgical or percutaneous repair of isolated primary mitral regurgitation.
Renormalization of scalar field theories in rational spacetime dimensions
Authors: Gracey J. A. 
Published: July 2020

AbstractWe renormalize various scalar field theories with a $$\phi ^n$$ϕn self interaction such as $$n=5$$n=5, 7 and 9 in their respective critical dimensions which are non-integer. The renormalization group functions for the O(N) symmetric extensions are also computed.
Rotameric Isomers of La2@C80 & Dodecafluoro-Subphthalocyanine Conjugate: Computational Characterization
Authors: Slanina Zdeněk , Uhlík Filip , Feng Lai , Akasaka Takeshi , Lu Xing , Adamowicz Ludwik 
Published: July 2020

Stability and spectra of rotamers of a previously via Prato reaction prepared conjugate of dimetallofullerene La2@C80 and dodecafluoro-subphthalocyanine with summary formula C113H10BF12La2N7O and bridging over the cage C–C bond between five- and six-membered rings are calculated. The inter-rotameric energetics is evaluated at the M06-2X/6-311G* ∼ SDD level while the entropy term with the M06-2X/3-21G ∼ SDD approach. The rotamer most-populated at room and higher temperatures has a structure in which both the nitrogen atom of the pyrrolidine ring and the dodecafluoro-subphthalocyanine moiety are inclined toward the five-membered ring belonging to the bridged-over C–C bond. The vibrational and electronic spectra are simulated and the latter spectrum agrees with the observed features. The calculated nanocarbon system is about the largest of its type computationally treated so far.
Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer
Authors: Carbone Michele , Harbour J. William , Brugarolas James , Bononi Angela , Pagano Ian , Dey Anwesha , Krausz Thomas , Pass Harvey I. , Yang Haining , Gaudino Giovanni 
Published: July 2020

Abstract
Among more than 200 BAP1-mutant families affected by the “BAP1 cancer syndrome,” nearly all individuals inheriting a BAP1 mutant allele developed one or more malignancies during their lifetime, mostly uveal and cutaneous melanoma, mesothelioma, and clear-cell renal cell carcinoma. These cancer types are also those that, when they occur sporadically, are more likely to carry somatic biallelic BAP1 mutations. Mechanistic studies revealed that the tumor suppressor function of BAP1 is linked to its dual activity in the nucleus, where it is implicated in a variety of processes including DNA repair and transcription, and in the cytoplasm, where it regulates cell death and mitochondrial metabolism. BAP1 activity in tumor suppression is cell type– and context-dependent. BAP1 has emerged as a critical tumor suppressor across multiple cancer types, predisposing to tumor development when mutated in the germline as well as somatically. Moreover, BAP1 has emerged as a key regulator of gene–environment interaction.
This article is highlighted in the In This Issue feature, p. 1079
Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer
Authors: Pennycuick Adam , Teixeira Vitor H. , AbdulJabbar Khalid , Raza Shan E. Ahmed , Lund Tom , Akarca Ayse U. , Rosenthal Rachel , Kalinke Lukas , Chandrasekharan Deepak P. , Pipinikas Christodoulos P. , Lee-Six Henry , Hynds Robert E. , Gowers Kate H.C. , Henry Jake Y. , Millar Fraser R. , Hagos Yeman B. , Denais Celine , Falzon Mary , Moore David A. , Antoniou Sophia , Durrenberger Pascal F. , Furness Andrew J. , Carroll Bernadette , Marceaux Claire , Asselin-Labat Marie-Liesse , Larson William , Betts Courtney , Coussens Lisa M. , Thakrar Ricky M. , George Jeremy , Swanton Charles , Thirlwell Christina , Campbell Peter J. , Marafioti Teresa , Yuan Yinyin , Quezada Sergio A. , McGranahan Nicholas , Janes Sam M. 
Published: July 2020

Abstract

Before squamous cell lung cancer develops, precancerous lesions can be found in the airways. From longitudinal monitoring, we know that only half of such lesions become cancer, whereas a third spontaneously regress. Although recent studies have described the presence of an active immune response in high-grade lesions, the mechanisms underpinning clinical regression of precancerous lesions remain unknown. Here, we show that host immune surveillance is strongly implicated in lesion regression. Using bronchoscopic biopsies from human subjects, we find that regressive carcinoma in situ lesions harbor more infiltrating immune cells than those that progress to cancer. Moreover, molecular profiling of these lesions identifies potential immune escape mechanisms specifically in those that progress to cancer: antigen presentation is impaired by genomic and epigenetic changes, CCL27–CCR10 signaling is upregulated, and the immunomodulator TNFSF9 is downregulated. Changes appear intrinsic to the carcinoma in situ lesions, as the adjacent stroma of progressive and regressive lesions are transcriptomically similar.

Significance:
Immune evasion is a hallmark of cancer. For the first time, this study identifies mechanisms by which precancerous lesions evade immune detection during the earliest stages of carcinogenesis and forms a basis for new therapeutic strategies that treat or prevent early-stage lung cancer.
See related commentary by Krysan et al., p. 1442.
This article is highlighted in the In This Issue feature, p. 1426
Identification of BBOX1 as a Therapeutic Target in Triple-Negative Breast Cancer
Authors: Liao Chengheng , Zhang Yang , Fan Cheng , Herring Laura E. , Liu Juan , Locasale Jason W. , Takada Mamoru , Zhou Jin , Zurlo Giada , Hu Lianxin , Simon Jeremy M. , Ptacek Travis S. , Andrianov Victor G. , Loza Einars , Peng Yan , Yang Huanghe , Perou Charles M. , Zhang Qing 
Published: July 2020

Abstract

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. Because of its heterogeneity and lack of hormone receptors or HER2 expression, targeted therapy is limited. Here, by performing a functional siRNA screening for 2-OG–dependent enzymes, we identified gamma-butyrobetaine hydroxylase 1 (BBOX1) as an essential gene for TNBC tumorigenesis. BBOX1 depletion inhibits TNBC cell growth while not affecting normal breast cells. Mechanistically, BBOX1 binds with the calcium channel inositol-1,4,5-trisphosphate receptor type 3 (IP3R3) in an enzymatic-dependent manner and prevents its ubiquitination and proteasomal degradation. BBOX1 depletion suppresses IP3R3-mediated endoplasmic reticulum calcium release, therefore impairing calcium-dependent energy-generating processes including mitochondrial respiration and mTORC1-mediated glycolysis, which leads to apoptosis and impaired cell-cycle progression in TNBC cells. Therapeutically, genetic depletion or pharmacologic inhibition of BBOX1 inhibits TNBC tumor growth in vitro and in vivo. Our study highlights the importance of targeting the previously uncharacterized BBOX1–IP3R3–calcium oncogenic signaling axis in TNBC.

Significance:
We provide evidence from unbiased screens that BBOX1 is a potential therapeutic target in TNBC and that genetic knockdown or pharmacologic inhibition of BBOX1 leads to decreased TNBC cell fitness. This study lays the foundation for developing effective BBOX1 inhibitors for treatment of this lethal disease.
This article is highlighted in the In This Issue feature, p. 1611
Value of Vascular and Non-Vascular Pattern on Computed Tomography Perfusion in Patients With Acute Isolated Aphasia
Authors: Rudilosso Salvatore , Rodríguez Alejandro , Amaro Sergio , Obach Víctor , Renú Arturo , Llull Laura , Laredo Carlos , Marín Ángel Alberto , Vargas Alberto , Urra Xabier , Chamorro Ángel 
Published: July 2020

Background and Purpose:
Acute onset aphasia may be due to stroke but also to other causes, which are commonly referred to as stroke mimics. We hypothesized that, in patients with acute isolated aphasia, distinct brain perfusion patterns are related to the cause and the clinical outcome. Herein, we analyzed the prognostic yield and the diagnostic usefulness of computed tomography perfusion (CTP) in patients with acute isolated aphasia.

Methods:
From a single-center registry, we selected a cohort of 154 patients presenting with acute isolated aphasia who had a whole-brain CTP study available. We collected the main clinical and radiological data. We categorized brain perfusion studies on CTP into vascular and nonvascular perfusion patterns and the cause of aphasia as ischemic stroke, transient ischemic attack, stroke mimic, and undetermined cause. The primary clinical outcome was the persistence of aphasia at discharge. We analyzed the sensitivity, specificity, positive and negative predictive values of perfusion patterns to predict complete clinical recovery and ischemic stroke on follow-up imaging.

Results:
The cause of aphasia was an ischemic stroke in 58 patients (38%), transient ischemic attack in 3 (2%), stroke mimic in 68 (44%), and undetermined in 25 (16%). CTP showed vascular and nonvascular perfusion pattern in 62 (40%) and 92 (60%) patients, respectively. Overall, complete recovery occurred in 116 patients (75%). A nonvascular perfusion pattern predicted complete recovery (sensitivity 75.9%, specificity 89.5%, positive predictive value 95.7%, and negative predictive value 54.8%), and a vascular perfusion pattern was highly predictive of ischemic stroke (sensitivity 94.8%, specificity 92.7%, positive predictive value 88.7%, and negative predictive value 96.7%). The 3 patients with ischemic stroke without a vascular perfusion pattern fully recovered at discharge.

Conclusions:
CTP has prognostic value in the workup of patients with acute isolated aphasia. A nonvascular pattern is associated with higher odds of full recovery and may prompt the search for alternative causes of the symptoms.
Acute Cerebrovascular Events in Hospitalized COVID-19 Patients
Authors: Rothstein Aaron , Oldridge Olivia , Schwennesen Hannah , Do David , Cucchiara Brett L. 
Published: July 2020

Background and Purpose:
Initial reports suggest a significant risk of thrombotic events, including stroke, in patients hospitalized with coronavirus disease 2019 (COVID-19). However, there is little systematic data on stroke incidence and mechanisms, particularly in racially diverse populations in the United States.

Methods:
We performed a retrospective, observational study of stroke incidence and mechanisms in all patients with COVID-19 hospitalized from March 15 to May 3, 2020, at 3 Philadelphia hospitals.

Results:
We identified 844 hospitalized patients with COVID-19 (mean age 59 years, 52% female, 68% Black); 20 (2.4%) had confirmed ischemic stroke; and 8 (0.9%) had intracranial hemorrhage. Of the ischemic stroke patients, mean age was 64 years, with only one patient (5%) under age 50, and 80% were Black. Conventional vascular risk factors were common, with 95% of patients having a history of hypertension and 60% a history of diabetes mellitus. Median time from onset of COVID symptoms to stroke diagnosis was 21 days. Stroke mechanism was cardioembolism in 40%, small vessel disease in 5%, other determined mechanism in 20%, and cryptogenic in 35%. Of the 11 patients with complete vascular imaging, 3 (27%) had large vessel occlusion. Newly positive antiphospholipid antibodies were present in >75% of tested patients. Of the patients with intracranial hemorrhage, 5/8 (63%) were lobar intraparenchymal hemorrhages, and 3/8 (38%) were subarachnoid hemorrhage; 4/8 (50%) were on extracorporeal membrane oxygenation.

Conclusions:
We found a low risk of acute cerebrovascular events in patients hospitalized with COVID-19. Most patients with ischemic stroke had conventional vascular risk factors, and traditional stroke mechanisms were common.
Pilot Study: Pneumatic Compression Garment Therapy for Postradiotherapy Laryngopharyngeal Edema
Authors: Tritter Andrew G. , Spiller Patrick T. , Brown Melanie L. , Weinberger Paul M. , Nathan Cherie-Ann O. 
Published: July 2020

Objectives: Pneumatic compression garment therapy (PCGT) has been established as treatment for postradiotherapy lymphedema, and its use in head and neck patients is becoming more common. Although effects on interstitial edema of the cervical soft tissues have been studied, effects on internal laryngopharyngeal edema, as well as associated symptoms of dysphagia and dysphonia, have yet to be published. Methods: We surveyed 7 patients treated with radiation for head and neck cancer (HNC) who had also been prescribed PCGT for cervical lymphedema. Patients were asked about subjective experience with the device, and also administered the Eating Assessment Tool-10 (EAT-10) and Voice Handicap Index-10 (VHI-10) surveys regarding their symptoms after using PCGT. Laryngoscopy videos from these same periods were also reviewed and scored using a validated tool for assessing laryngopharyngeal edema. Results: 85% of patients reported at least some improvement in dysphagia and dysphonia following PCGT. Average EAT-10 score after PCGT was 11.4 and average VHI-10 score after PCGT was 8.7. These compare more favorably to historical scores for the same questionnaires in similar patient populations. Laryngeal edema scores on endoscopic examination were not significantly different after at least 3 months of therapy (pre: 20.15, post: 20.21, P = .975); however, the utility of this result is limited by a low inter-rater reliability (Krippendorff α = .513). Conclusions: While we are unable to show any difference in objective assessment of laryngopharyngeal edema on endoscopic examination in this small pilot study, patients report substantial subjective improvement in postradiotherapy dysphagia and dysphonia following cervical PCGT that warrants more formal investigation.