bluuebunny/crossref_metadata_2025_split huggingface dataset:
Principles of neuroanatomical architecture supporting brain–immune cell–cell interactions
Authors: Shimada Atsuyoshi 
Published: December 2019

AbstractThe brain interacts with the immune system under inflammatory and non‐inflammatory conditions. Brain cells have the capacity to produce a variety of cytokines in response to systemic immune activation. Therefore, we hypothesized that brain cells and immune cells move close to each other, so that they can carry out intercellular interactions. In the present article, I review our studies to determine the site for the brain–immune cell–cell interactions. The leptomeninges, choroid plexus stroma and epithelium, attachments of the choroid plexuses, vascular endothelial cells, cells of the perivascular space, and astrocytic end‐feet compose the histological architecture that supports interactions between bone marrow‐derived myeloid cells and brain parenchymal cells under non‐inflammatory conditions. This architecture also functions as the interface at which systemic inflammation‐induced responses can be conveyed to the brain parenchyma under inflammatory conditions. It should be noted that such brain–immune interactions occur in the absence of florid inflammatory cell infiltrates in the brain parenchyma, and with relative preservation of the blood‐brain barrier. Rather, cells comprising the blood‐brain barrier act as the interface linking peripheral immune activation and brain responses. These responses, known as “neuroinflammation”, are unique to the brain. Neuroinflammation differs from the histological inflammation that is accompanied by a florid infiltration of the leptomeninges (meningitis) and/or brain parenchyma (encephalitis) by inflammatory cells. In this review, the relevance of histological studies to unravel the mechanisms linking systemic inflammation, brain–immune interface cells and brain parenchymal cells, with a special emphasis on sepsis‐associated encephalopathy, is discussed.
Three novel patients with epileptic encephalopathy due to biallelic mutations in the PLCB1 gene
Authors: Desprairies Camille , Valence Stéphanie , Maurey Hélène , Helal Suzette I. , Weckhuysen Sarah , Soliman Hala , Mefford Heather C. , Spentchian Myrtille , Héron Delphine , Leguern Eric , Nava Caroline , Bouilleret Viviane , Moretti Raffaella , Mignot Cyril 
Published: December 2019

AbstractBiallelic mutations in the PLCB1 gene, encoding for a phospholipase C beta isoform strongly expressed in the brain, have been reported to cause infantile epileptic encephalopathy in only four children to date. We report here three additional patients to delineate the phenotypic and genotypic characteristics of the disease. Our three patients were one sporadic case with an intragenic homozygous deletion and two cousins with the homozygous p.(Arg222*) nonsense variant in PLCB1. These patients had severe to profound intellectual disability, epileptic spasms at age 3‐5 months concomitant with developmental arrest or regression, other seizure types and drug‐resistant epilepsy. With this report, we expand the clinical, radiologic and electroencephalographic knowledge about the extremely rare PLCB1‐related encephalopathy. Since the first report in 2010, the overall number of reported patients with our additional patients is currently limited to seven. All seven patients had epileptic encephalopathy, mainly infantile spasms and 6/7 had profound intellectual disability, with one only being able to walk. Truncal hypotonia was the most frequent neurological sign, sometimes associated with pyramidal and/or extrapyramidal hypertonia of limbs. Microcephaly was inconstant. In conclusion, the phenotypical spectrum of PLCB1‐related encephalopathy is relatively narrow, comprises infantile spasms and severe to profound intellectual disability, and does not seem to define a recognizable clinical entity.
Prognostic ability of the distance‐saturation product in the 6‐minute walk test in patients with chronic obstructive pulmonary disease
Authors: Gurbani Nikita , Figueira Gonçalves Juan Marco , García Bello Miguel Ángel , García‐Talavera Ignacio , Afonso Díaz Andrea 
Published: December 2019

AbstractIntroductionThe product (DSP) of the distance walked (meters) and minimum oxygen saturation obtained during the 6‐minute walk test (6MWT) has been proposed as a predictor of mortality in idiopathic pulmonary fibrosis and in bronchiectasis not related to cystic fibrosis.ObjectiveThe aim of this study was to determine the DSP's ability to predict mortality in patients with chronic obstructive pulmonary disease (COPD) at the outpatient level and compare it to the BODE index and meters walked in the 6MWT.Material and methodsDescriptive observational study in a cohort of patients with COPD being treated at outpatient pulmonology clinics. Each of the patients completed the 6MWT following ATS/ERS protocols and their BODE index and DSP were calculated.ResultsAbout 103 patients were included. The average length of follow‐up was 36 months. Patients who died showed a lower number of meters walked in the 6MWT (P < 0.001), as well as a lower DSP (P < 0.001). A 6MWT < 334 m, a DSP < 290 and a BODE ≥ 4 showed good prognostic ability at 3 years (AUC 71%, 69% and 70.4%, respectively). The 6MWT was superior to the BODE index in predicting mortality during the first year of follow‐up (P = 0.023). We did not find any differences between DSP and meters walked in the 6MWT.ConclusionsThe DSP is a good predictor of mortality, although it does not offer a better prognostic ability than that of meters walked in the 6MWT.
Efficacy and safety of endoscopic submucosal dissection using a scissors‐type knife with prophylactic over‐the‐scope clip closure for superficial non‐ampullary duodenal epithelial tumors
Authors: Dohi Osamu , Yoshida Naohisa , Naito Yuji , Yoshida Takuma , Ishida Tsugitaka , Azuma Yuka , Kitae Hiroaki , Matsumura Shinya , Takayama Shun , Ogita Kazuyuki , Mizuno Naoki , Nakano Takahiro , Majima Atsushi , Hirose Ryohei , Inoue Ken , Kamada Kazuhiro , Uchiyama Kazuhiko , Takagi Tomohisa , Ishikawa Takeshi , Konishi Hideyuki , Morinaga Yukiko , Kishimoto Mitsuo , Itoh Yoshito 
Published: December 2019

Background and study aimThis study aimed to assess the safety and feasibility of endoscopic submucosal dissection (ESD) using a scissors‐type knife with prophylactic closure using over‐the‐scope clip (OTSC) for superficial non‐ampullary duodenal epithelial tumors (SNADETs).Patients and methodsConsecutive patients who underwent ESD for SNADETs >10 mm between January 2009 and July 2019 were retrospectively enrolled. We performed ESD using either a needle‐type knife (Flush Knife‐ESD) or a scissors‐type knife (Clutch Cutter‐ESD). Mucosal defects were prophylactically closed using three methods: conventional clip, laparoscopic closure, or OTSC.ResultsA total of 84 lesions were resected using the Flush Knife‐ESD and the Clutch Cutter‐ESD (37 and 47 patients, respectively), and conventional clip, laparoscopic closure, and OTSC for mucosal defect closure after ESD were applied in 13, 13, and 56 lesions, respectively. The R0 resection rate was significantly higher in the Clutch Cutter‐ESD than that in the Flush Knife‐ESD (97.9% vs 83.8%, respectively, P = 0.040). The intraoperative perforation rate was significantly lower in the Clutch Cutter‐ESD than in the Flush Knife‐ESD (0% vs 13.5%, respectively, P = 0.014). Complete closure rates of conventional clip, laparoscopic closure, and OTSC were 76.9%, 92.3%, and 98.2%, respectively (P = 0.021); and delayed perforation rates were 15.4%, 7.7%, and 1.8%, respectively (P = 0.092).ConclusionsEndoscopic submucosal dissection using a scissors‐type knife with prophylactic OTSC closure is safe and feasible for the low‐invasive treatment of SNADETs.
Risk factor analysis for adverse events and stent dysfunction of endoscopic ultrasound‐guided choledochoduodenostomy
Authors: Matsumoto Shimpei , Hara Kazuo , Mizuno Nobumasa , Kuwahara Takamichi , Okuno Nozomi , Obata Masahiro , Kurita Yusuke , Koda Hiroki , Tajika Masahiro , Tanaka Tsutomu , Hirayama Yutaka , Onishi Sachiyo , Toriyama Kazuhiro , Niwa Yasumasa 
Published: December 2019

Background and AimsAlthough the technique of endoscopic ultrasound‐guided choledochoduodenostomy (EUS‐CDS) is becoming standardized, its safety issues have not been sufficiently investigated. Therefore, we aimed to identify factors associated with adverse events and stent patency in EUS‐CDS.MethodsConsecutive patients who underwent EUS‐CDS between September 2003 and July 2017 were included. Technical/clinical success, adverse events and stent dysfunctions were analyzed retrospectively.ResultsA total of 151 patients underwent EUS‐CDS. In nine patients, procedures were discontinued before puncture. Technical and clinical success rates were 96.5% (137/142) and 98.5% (135/137), respectively. The adverse event rate was 20.4% (29/142). As a risk factor for peritonitis, plastic stents (PS) showed a significantly high odds ratio (OR) compared with covered self‐expandable metal stents (CSEMS; OR, 4.31; P = 0.030). CSEMS cases showed a significantly longer patency period than PS cases (329 vs 89 days; HR, 0.35; P < 0.001). As a risk factor for early stent dysfunction (within 14 days), stent direction to the oral side showed a significantly high OR (OR, 43.47; P < 0.001). In cases with oblique‐viewing EUS, double penetration of the duodenum occurred at significantly higher frequency than in cases with forward‐viewing EUS (7.0 vs 0.0%; P = 0.024).ConclusionsPlastic stents and stent direction to the oral side were risk factors for peritonitis and early stent dysfunction, respectively. Using covered self‐expandable metal stents and changing stent direction to the anal side seemed appropriate to prevent peritonitis and early stent dysfunction.
Improvement of clinical outcome in patients with ST‐elevation myocardial infarction between 1999 and 2016 in China: The Prospective, Multicentre Registry MOODY study
Authors: Chen Mengxuan , Kan Jing , Zhang Jun‐Jie , Tian Nailiang , Ye Fei , Yang Song , Chen Shao‐Liang ,   On behalf of MOODY Regustry study Investigators
Published: December 2019

AbstractBackgroundReports showed no change of 7‐day mortality after primary percutaneous coronary intervention (PCI) for ST‐elevation myocardial infarction (STEMI) between 2001 and 2011 in China. National rolling one‐year interventional standardized training programme began in September 2009. However, the improvement in clinical outcome following STEMI PCI after 2011 remains unclear.Methods and ResultsThis multicentre MOODY registry study aimed to analyse the clinical improvement after STEMI PCI. Of a total of 9265 acute MI patients registered from 24 centres, 3142 STEMIs having a first medical contact time ≤12 hours and undergoing primary PCI were assigned to the Pre Group (n = 1014, between March 1999 and October 2010) or the Post Group (n = 2128, between 2010 November and 2016 October). The primary endpoint was in‐hospital cardiac death. Study endpoints were also compared between trained and untrained operators and between experienced (≥50 primary PCIs/year) and inexperienced personnel. In‐hospital death after PCI was 3.0% in the Pre Group, significantly higher than 1.6% in the Post Group (P = .035). The improvements in clinical outcome after PCI between the 2016 and Pre Groups were stably sustained through one‐year follow‐up. The significant reduction for in‐hospital death was noted when primary PCI was performed by trained (1.4% vs 5.4%, P < .001) or experienced (2.7% vs 4.8%, P = .001) operators, compared to untrained or inexperienced operators, respectively. Inclusion of the untrained operator into the conventional risk model strongly enhanced the prediction for endpoints. Age, Killip Class 3, diabetes, trans‐radial approach and system delay were five predictors of in‐hospital death after primary PCI.ConclusionPCI for STEMI by a trained and experienced operator was associated with significant reduction of in‐hospital death. Our results strongly warrant the need for promoting the current system response and patient education.
Threats to at‐risk salmonids of the Canadian Rocky Mountain region
Authors: Sinnatamby R. Niloshini , Cantin Ariane , Post John R. 
Published: December 2019

AbstractTrout and charr, members of the salmonid family, have high conservation value but are also susceptible to anthropogenic threats in part due to the specificity of their habitat requirements. Understanding historical and future threats facing these species is necessary to promote their recovery. Of freshwater trout and charr in the Canadian Rocky Mountain region, westslope cutthroat trout (Oncorhynchus clarkii lewisi), bull trout (Salvelinus confluentus; a charr species) and Athabasca rainbow trout (Oncorhynchus mykiss) are of conservation concern. And indeed, range contractions and declining populations are evident throughout much of their ranges. Range contraction was most evident in the southern Alberta designatable unit (DU) of westslope cutthroat trout. Diminished populations were also evident in the downstream watersheds of the Alberta bull trout range, and throughout the Athabasca rainbow trout range. We assessed historical and future threats to evaluate the relative importance of individual threats to each DU and compare their impact among species. Individual threats fall into the broad categories of angling, non‐native species and genes, habitat loss and alteration, and climate change. Severity of each threat varies by DU and reflects the interaction between species’ biology and the location of the DU. Severity of threats facing each DU has changed over time, reflecting extirpation of native populations, changes in management and industry best practices, expansion of non‐native species and progressing climate change. The overall threat impact for each DU indicates a high probability of substantial and continuing declines and calls for immediate action.
N400 event‐related brain potential as an index of real‐world and neurocognitive function in patients at clinical high risk for schizophrenia
Authors: Lepock Jennifer R. , Ahmed Sarah , Mizrahi Romina , Gerritsen Cory J. , Maheandiran Margaret , Bagby R. Michael , Korostil Michele , Kiang Michael 
Published: December 2019

AbstractAimThe N400 event‐related potential is a neurophysiological index of cognitive processing of real‐world knowledge. In healthy populations, N400 amplitude is smaller in response to stimuli that are more related to preceding context. This ‘N400 semantic priming effect’ is thought to reflect activation of contextually related information in semantic memory (SM). N400 semantic priming deficits have been found in schizophrenia, and in patients at clinical high risk (CHR) for this disorder. Because this abnormality in processing relationships between meaningful stimuli could affect ability to navigate everyday situations, we hypothesized it would be associated with real‐world functional impairment in CHR patients. Second, we hypothesized it would correlate with global neurocognitive impairment in this group.MethodsWe measured N400 semantic priming in 35 CHR patients who viewed prime words each followed by a related or unrelated target word, at stimulus‐onset asynchrony (SOA) of 300 or 750 ms. We measured academic/occupational and social function with the global function (GF): Role and Social scales, and cognitive function with the MATRICS Consensus Cognitive Battery (MCCB).ResultsDecreased N400 semantic priming at the 300‐ms SOA correlated with lower GF:Role scores. Decreased N400 semantic priming at the 750‐ms SOA correlated with lower MCCB composite scores.ConclusionsDeficits in activating contextually related concepts in SM over short time intervals may contribute to functional impairment in CHR patients. Furthermore, N400 priming deficits over longer intervals may be a biomarker of global cognitive dysfunction in this population. Longitudinal studies are needed to determine whether these deficits are associated with schizophrenia risk within this population.
A Way through the woods: Development of an integrated care pathway for adolescents with depression
Authors: Courtney Darren , Bennett Kathryn , Henderson Joanna , Darnay Karleigh , Battaglia Marco , Strauss John , Watson Priya , Szatmari Peter 
Published: December 2019

AbstractAimsDepression in adolescents is common and debilitating. Treatment approaches vary widely across clinics and may not reflect evidence‐based care. Integrated care pathways (ICPs) are implementation tools to facilitate bridging the gap between rigorous but often complex clinical practice guidelines and what is actually practiced. We describe the development of an ICP for the treatment of Adolescents with Major Depressive Disorder (MDD‐A) based on the best‐available clinical practice guidelines and derived in collaboration with clinicians, administrators, youth partners and caregivers.MethodsWith clinician and health service manager input, we took the recommendations from a high quality clinical practice guideline (the National Institute of Health and Care Excellence Clinical Practice Guideline for Depression in Children and Young People) and translated them into an ICP. Feedback from youth partners and clinicians was iteratively incorporated into the current version of the pathway using a collaborative approach.ResultsThe current iteration of the pathway at a Canadian tertiary care teaching hospital is described. All youth (and caregivers, if applicable) are offered a multi‐family psychoeducation session, a 16‐session Group Cognitive Behaviour Therapy and team reviews every 4 weeks that include measurement‐based care. Conditional branches of the pathway include a medication algorithm and an 8‐session group for caregivers.ConclusionsThe resulting ICP provides a tool to facilitate bridging the gap between evidence and clinical practice.
Screening for the at‐risk mental state in educational settings: A systematic review
Authors: Howie Clare , Potter Claire , Shannon Ciaran , Davidson Gavin , Mulholland Ciaran 
Published: December 2019

AbstractAimThe at‐risk mental state (ARMS) allows clinicians to identify individuals who have an increased risk of developing psychosis. At present, most screening for psychosis‐risk is carried out within help‐seeking populations; however, screening within educational settings may allow clinicians to identify individuals at‐risk earlier and to increase the rate of detection. This review aimed to examine screening for the ARMS in educational settings, with the key questions: what screening tools have been used in educational settings, can screening in educational settings detect individuals with ARMS, what threshold scores in screening tools indicate a positive screen in educational settings, are there comorbid mental health conditions associated with the ARMS in educational settings?MethodsSearches were carried out in PsycINFO, MEDLINE, EMBASE, Scopus and Web of Science and reference lists of included articles searched. Results were summarized using narrative synthesis.ResultsNine papers were included for narrative synthesis. A variety of screening tools have been used when screening for the ARMS in educational settings. The majority of studies have been conducted in schools. The prevalence of the ARMS reported in ranges from 1% to 8%.ConclusionsThe ARMS indicates the presence of distressing symptoms for which intervention may be beneficial. Screening programmes within educational settings may allow outreach for prodromal symptoms at an earlier stage than clinical settings currently provided for.
A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma
Authors: Hajek Roman , Pour Ludek , Ozcan Muhit , Martin Sánchez Jesus , García Sanz Ramon , Anagnostopoulos Achilles , Oriol Albert , Cascavilla Nicola , Terjung Andreas , Lee Yihua , Briso Eva M. , Dobkowska Edyta , Hauns Bernhard , Špička Ivan 
Published: December 2019

AbstractObjectiveWe evaluated ibrutinib, a once‐daily inhibitor of Bruton's tyrosine kinase, combined with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma who had received 1‐3 prior therapies.MethodsThis was a phase 2, single‐arm, open‐label, multicentre study (NCT02902965). The primary endpoint was progression‐free survival (PFS).ResultsSeventy‐six patients were enrolled; 74 received ≥1 dose of study treatment. After median follow‐up of 19.6 months, median PFS was 8.5 months (95% CI: 6.2‐10.8); median overall survival was not reached. Overall response rate was 57% (95% CI: 45‐68), and median duration of response was 9.5 months (95% CI: 6.9‐10.6). Grade 3/4 AEs occurred in 73% of patients and fatal AEs occurred in 15% of patients. Incidence of major haemorrhage was 5%; one patient died from cerebral haemorrhage. After an observed increased incidence of serious (42%) and fatal (11%) infections, enrolment was suspended to implement risk‐minimisation measures. The safety profile was otherwise consistent with known safety profiles of the individual drugs.ConclusionIbrutinib combined with bortezomib and dexamethasone elicited clinical responses. However, efficacy assessments conducted at potential restart of enrolment indicated that the targeted PFS could not be reached with additional patient enrolment, and the study was terminated.
B cell maturation antigen‐specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: A meta‐analysis
Authors: Gagelmann Nico , Ayuk Francis , Atanackovic Djordje , Kröger Nicolaus 
Published: December 2019

AbstractIntroductionChimeric antigen receptor (CAR) T cells targeting B cell maturation antigen (BCMA) have shown impressive results in clinical studies for relapsed/refractory multiple myeloma (RRMM). We performed a systematic literature review to summarize the current body of evidence on the role of anti‐BCMA CAR T cells for RRMM.Objectives and MethodsFifteen studies comprising a total of 285 patients with heavily pretreated RRMM were included using a conventional meta‐analysis. Main efficacy outcomes were response, relapse, and survival. Safety outcomes were cytokine release syndrome (CRS) and neurotoxicity.ResultsAnti‐BCMA CAR T cells resulted in a pooled overall response of 82% (95% confidence interval [CI], 74%‐88%) and complete response of 36% (24%‐50%). Higher CAR+ cell doses were associated with higher response rates. The pooled relapse rate of responders was 45% (27%‐64%), and median progression‐free survival was 10 months. Present extramedullary disease did not show worse outcome. Severe CRS grades 3‐4 and neurotoxicity occurred in 15% (10%‐23%) and 18% (10%‐31%).ConclusionAnti‐BCMA CAR T cells showed high response rates, even in patients with present extramedullary disease, while relapse occurred in half of the patients who achieved a response. Larger studies with longer follow‐up especially evaluating the association of response and survival are needed.