bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robustness of CSF Aβ42/40 and Aβ42/P‐tau181 measured using fully automated immunoassays to detect AD‐related outcomes
Authors: Leuzy Antoine , Mattsson‐Carlgren Niklas , Cullen Nicholas C. , Stomrud Erik , Palmqvist Sebastian , La Joie Renaud , Iaccarino Leonardo , Zetterberg Henrik , Rabinovici Gil , Blennow Kaj , Janelidze Shorena , Hansson Oskar 
Published: January 2023

AbstractIntroductionThis study investigated the comparability of cerebrospinal fluid (CSF) cutoffs for Elecsys immunoassays for amyloid beta (Aβ)42/Aβ40 or Aβ42/phosphorylated tau (p‐tau)181 and the effects of measurement variability when predicting Alzheimer's disease (AD)‐related outcomes (i.e., Aβ‐positron emission tomography [PET] visual read and AD neuropathology).MethodsWe studied 750 participants (BioFINDER study, Alzheimer's Disease Neuroimaging Initiative [ADNI], and University of California San Francisco [UCSF]). Youden's index was used to identify cutoffs and to calculate accuracy (Aβ‐PET visual read as outcome). Using longitudinal variability in Aβ‐negative controls, we identified a gray zone around cut‐points where the risk of an inconsistent predicted outcome was >5%.ResultsFor Aβ42/Aβ40, cutoffs across cohorts were <0.059 (BioFINDER), <0.057 (ADNI), and <0.058 (UCSF). For Aβ42/p‐tau181, cutoffs were <41.90 (BioFINDER), <39.20 (ADNI), and <46.02 (UCSF). Accuracy was ≈90% for both Aβ42/Aβ40 and Aβ42/p‐tau181 using these cutoffs. Using Aβ‐PET as an outcome, 8.7% of participants fell within a gray zone interval for Aβ42/Aβ40, compared to 4.5% for Aβ42/p‐tau181. Similar findings were observed using a measure of overall AD neuropathologic change (7.7% vs. 3.3%). In a subset with CSF and plasma Aβ42/40, the number of individuals within the gray zone was ≈1.5 to 3 times greater when using plasma Aβ42/40.DiscussionCSF Aβ42/p‐tau181 was more robust to the effects of measurement variability, suggesting that it may be the preferred Elecsys‐based measure in clinical practice and trials.
Prediction of neuropathologic lesions from clinical data
Authors: Phongpreecha Thanaphong , Cholerton Brenna , Bukhari Syed , Chang Alan L. , De Francesco Davide , Thuraiappah Melan , Godrich Dana , Perna Amalia , Becker Martin G. , Ravindra Neal G. , Espinosa Camilo , Kim Yeasul , Berson Eloise , Mataraso Samson , Sha Sharon J. , Fox Edward J. , Montine Kathleen S. , Baker Laura D. , Craft Suzanne , White Lon , Poston Kathleen L. , Beecham Gary , Aghaeepour Nima , Montine Thomas J. 
Published: January 2023

AbstractINTRODUCTIONPost‐mortem analysis provides definitive diagnoses of neurodegenerative diseases; however, only a few can be diagnosed during life.METHODSThis study employed statistical tools and machine learning to predict 17 neuropathologic lesions from a cohort of 6518 individuals using 381 clinical features (Table S1). The multisite data allowed validation of the model's robustness by splitting train/test sets by clinical sites. A similar study was performed for predicting Alzheimer's disease (AD) neuropathologic change without specific comorbidities.RESULTSPrediction results show high performance for certain lesions that match or exceed that of research annotation. Neurodegenerative comorbidities in addition to AD neuropathologic change resulted in compounded, but disproportionate, effects across cognitive domains as the comorbidity number increased.DISCUSSIONCertain clinical features could be strongly associated with multiple neurodegenerative diseases, others were lesion‐specific, and some were divergent between lesions. Our approach could benefit clinical research, and genetic and biomarker research by enriching cohorts for desired lesions.
Selective Removal of Sulfate from Water by Precipitation with a Rigid Bis‐amidinium Compound
Authors: Tzioumis Nikki A. , Cullen Duncan A. , Jolliffe Katrina A. , White Nicholas G. 
Published: January 2023

AbstractA simple, readily prepared biphenyl bis‐amidinium compound (1⋅Cl2) is able to selectively precipitate sulfate from water. The precipitant is effective at concentrations as low as 1 mM and shows complete selectivity against monovalent anions, and high selectivity even against CO32− and HPO42−. It is highly effective (>90 % sulfate removed) in both seawater and highly acidic conditions relevant to mining waste‐streams. X‐ray crystallography reveals that 1⋅SO4 forms a tightly packed, anhydrous, structure where each sulfate anion receives eight hydrogen bonds from amidinium N−H hydrogen bond donors.
Cinchonine‐induced cell death in pancreatic cancer cells by downregulating RRP15
Authors: Liang Feng , Lv Ying , Qiao Xiao , Zhang Shu , Shen Shanshan , Wang Changcheng , Xu Guifang , Zou Xiaoping , Wang Lei , Zhang Bin 
Published: January 2023

AbstractPancreatic cancer is characterized by poor prognosis and high mortality, while its treatment remains unsatisfactory. Cinchonine, a natural compound present in cinchona bark, is a potential anticancer drug. Whether cinchonine is of relevance to pancreatic cancer therapeutics is unclear. This research showed that the ribosomal RNA‐processing 15 homolog (RRP15) expression is decreased in the pancreatic cancer, and RRP15 knockdown inhibited autophagy, and caused apoptosis in pancreatic cancer cells. Cinchonine treatment inhibits the expression of RRP15 and autophagy, and caused apoptosis by leading to the activation of Nrf2 axis in pancreatic cancer cells. Taken together, the above results indicate that cinchonine treatment inhibited autophagy and induced apoptosis through activating Nrf2 axis by downregulating RRP15 in pancreatic cancer cells.
Percutaneous coronary intervention with drug‐coated balloon‐only strategy combined with single antiplatelet treatment in patients at high bleeding risk: Single center experience of a novel concept
Authors: Räsänen Alma , Kärkkäinen Jussi M. , Eranti Antti , Eränen Jaakko , Rissanen Tuomas T. 
Published: January 2023

AbstractObjectivesAt least 1 month of dual antiplatelet therapy is required after coronary stenting. The aim of this all‐comers retrospective registry study was to assess the efficacy and safety of percutaneous coronary intervention (PCI) using drug‐coated balloon (DCB) with single antiplatelet treatment (SAPT).MethodsBetween 2011 and 2020, 232 PCIs were performed in 172 patients using the DCB‐only strategy and discharged with SAPT.ResultsThe mean age of the patients was 75 ± 11 years and 59% were male. The clinical presentation was stable coronary artery disease (CAD) in 42% of the patients and acute coronary syndrome (ACS) in 58%. The lesions were mainly de novo (96%). The majority (58%) of treated lesions were in large coronary arteries (≥3.0 mm). Most (87%) of the patients were at high bleeding risk (HBR) with at least one major or two minor Academic Research Consortium (ARC) risk factors for bleeding. Periprocedural DAPT was used in 49% of the patients. The 12‐month major adverse cardiac events (MACE, the composition of cardiovascular death, nonfatal myocardial infarction, and target‐lesion revascularization) rate was 1.4% in stable CAD and 7.1% in ACS. The 12‐month all‐cause mortality after DBC only + SAPT strategy was 4.1% in stable CAD and 12.1% in ACS. The rate of ischemia‐driven target lesion revascularisation (TLR) was 0% in stable CAD and 3.0% in ACS at 12 months. The 12‐month rate of significant bleeding (BARC type 2‐5) was 10.5%. There were no acute or subacute vessel closures.ConclusionsDespite the aged patient population with comorbidities, the TLR, MACE, and bleeding rates were low with DCB‐only PCI combined with SAPT. This novel approach could reduce the post‐PCI bleeding risk in patients with CAD and HBR compared to stenting.
Validation of the new PROGRESS‐CTO complication risk scores in the OPEN‐CTO registry
Authors: Azzalini Lorenzo , Hirai Taishi , Salisbury Adam , Gosch Kensey , Sapontis James , Nicholson William J. , Karmpaliotis Dimitri , Moses Jeffrey W. , Kearney Kathleen E. , Lombardi William L. , Grantham James Aaron 
Published: January 2023

AbstractBackgroundRisk stratification before chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is important to inform procedural planning as well as patients and their families. We sought to externally validate the PROGRESS‐CTO complication risk scores in the OPEN‐CTO registry.MethodsOPEN‐CTO is a prospective registry of 1000 consecutive CTO PCIs performed at 12 experienced US centers using the hybrid algorithm. Endpoints of interest were in‐hospital all‐cause mortality, need for pericardiocentesis, acute myocardial infarction (MI), and major adverse cardiovascular events (MACE) (a composite of all‐cause mortality, stroke, periprocedural MI, urgent repeat revascularization, and tamponade requiring pericardiocentesis). Model discrimination was assessed with the area under the curve (AUC) method, and calibration with the observed‐versus‐predicted probability method.ResultsMean age was 65.4 ± 10.3 year, and 36.5% of patients had prior coronary artery bypass graft. Overall, 41 patients (4.1%) suffered MACE, 9 (0.9%) mortality, 26 (2.6%) acute MI, and 11 (1.1%) required pericardiocentesis. Technical success was achieved in 86.3%. Patients who experienced MACE had higher anatomic complexity, and more often required antegrade dissection/reentry and the retrograde approach. Increasing PROGRESS‐CTO MACE scores were associated with increasing MACE rates: 0.5% (score 0−1), 2.4% (score 2), 3.7% (score 3), 4.5% (score 4), 7.8% (score 5), 13.0% (score 6−7). The AUC were as follows: MACE 0.72 (95% confidence interval [CI]: 0.66−0.78), mortality 0.79 (95% CI: 0.66−0.95), pericardiocentesis 0.71 (95% CI: 0.60−0.82), and acute MI 0.57 (95% CI: 0.49−0.66). Calibration was adequate for MACE and mortality, while the models underestimated the risk of pericardiocentesis and acute MI.ConclusionsIn a large external cohort of patients treated with the hybrid algorithm by experienced CTO operators, the PROGRESS‐CTO MACE, mortality, and pericardiocentesis risk scores showed good discrimination, while the acute MI score had inferior performance.
Role of the retrograde Carlino technique for chronic total occlusion percutaneous coronary intervention
Authors: Azzalini Lorenzo , Boudou Nicolas , Avran Alexandre , Kane Jesse , Lombardi William L. , Kearney Kathleen E. , Carlino Mauro 
Published: January 2023

AbstractBackgroundThere is scarce data on the outcomes of the Carlino technique for chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We aimed to investigate the indications and outcomes of the Carlino technique as performed in the context of the retrograde approach.MethodsWe pooled CTO PCI cases where a retrograde Carlino technique was performed from high‐volume operators at four centers. The Carlino technique was characterized according to its indication (achieving plaque/cap modification, clarifying microcatheter location within the vessel, resolving distal cap ambiguity) and was considered successful when it led to the desired outcome.ResultsA total of 43 patients were included. Occlusion complexity was very high (mean J‐CTO score 3.3 ± 0.8). The two most common indications were understanding the anatomy of the occlusion and clarifying gear location (37.2%) and impenetrable distal cap (34.9%). The Carlino technique was successful in 88.4% of cases. Overall technical and procedural success was 86.0%. The most common successful crossing technique was reverse controlled antegrade and retrograde subintimal tracking (70.3%). No complications were attributed to the Carlino technique.ConclusionsWe observed a high success rate of the retrograde Carlino technique, as well as overall technical and procedural success rates. No Carlino technique‐related complications were observed. Additional data from larger registries are warranted to further confirm the safety and efficacy of this technique.
ABCB1 Gene Variants and Antidepressant Treatment Outcomes: A Systematic Review and Meta‐Analysis Including Results from the CAN‐BIND‐1 Study
Authors: Magarbeh Leen , Hassel Claudia , Choi Maximilian , Islam Farhana , Marshe Victoria S. , Zai Clement C. , Zuberi Rayyan , Gammal Roseann S. , Men Xiaoyu , Scherf‐Clavel Maike , Enko Dietmar , Frey Benicio N. , Milev Roumen , Soares Claudio N. , Parikh Sagar V. , Placenza Franca , Strother Stephen C. , Hassel Stefanie , Taylor Valerie H. , Leri Francesco , Blier Pierre , Farzan Faranak , Lam Raymond W. , Turecki Gustavo , Foster Jane A. , Rotzinger Susan , Kloiber Stefan , Kennedy James L. , Kennedy Sidney H. , Bousman Chad A. , Müller Daniel J. 
Published: January 2023

The P‐glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta‐analysis to investigate the association between six ABCB1 single‐nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN‐BIND‐1) cohort. For the CAN‐BIND‐1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta‐analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta‐analysis if they investigated at least one ABCB1 SNP in individuals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN‐BIND‐1 sample. A total of 39 studies were included in the systematic review. In the meta‐analysis, we observed a significant association between rs1128503 and treatment response (T vs. C‐allele, odds ratio = 1.30, 95% confidence interval = 1.15–1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended.
Environmental DNA of Antarctic krill (Euphausia superba): Measuring DNA fragmentation adds a temporal aspect to quantitative surveys
Authors: Suter Leonie , Wotherspoon Simon , Kawaguchi So , King Rob , MacDonald Anna J. , Nester Georgia M. , Polanowski Andrea M. , Raymond Ben , Deagle Bruce E. 
Published: January 2023

AbstractAntarctic krill (Euphausia superba) is a keystone species in the Southern Ocean ecosystem, and monitoring its distribution and abundance is crucial for the sustainable management of expanding fisheries targeting the species. Environmental DNA (eDNA)‐based monitoring could complement conventional krill surveys, but its applicability is limited by a lack of knowledge on eDNA persistence and decay in the Southern Ocean. We aimed to develop a method that can not only quantify Antarctic krill eDNA, but also estimate a relative time since this eDNA was shed (“recent” vs “older”). Three species‐specific qPCR markers targeting the mitochondrial 16S region were developed, and the eDNA decay characteristics of these markers were determined through tank experiments. Krill eDNA was partially degraded in all samples, even when krill were present. Marker concentrations decreased exponentially at similar rates after krill removal, with initial relative abundances maintained across the three markers. Over time, the concentration of the longest marker decreased faster, changing the relative abundances of the markers, and allowing discrimination of more recent samples from more degraded older samples. We employed this new method to quantify Antarctic krill eDNA collected across a 4800 km Southern Ocean transect, and estimated the age of the eDNA in these samples based on the relative abundance of markers, adding a temporal aspect to a quantitative eDNA survey. We also compared a Euphausiid‐specific metabarcoding marker to the qPCR method to assess sensitivity in detecting Antarctic krill eDNA. While these new eDNA methods should be evaluated against existing non‐molecular survey methods, they could add an important novel, dynamic layer of information to future krill surveys. Our method could not only determine where Antarctic krill eDNA is present but shed light on how they may be using certain habitats, expanding our understanding of this important species’ life cycle and contributing to more accurate abundance and distribution estimates.
Bacillus Calmette–Guérin–induced interleukin‐10 inhibits S100A8/A9 production and hinders development of T helper type 1 memory in mice
Authors: Wang Yaping , Sun Yuehua , Zheng Yong , Yang Yuling , He Liu , Qu Peijie , Zhou Fangting , Xu XiaoXu , Bai Xuanchang , Chen Xin , Yuan Yangxuan , Liu Min , Pan Qin 
Published: January 2023

AbstractTuberculosis caused by Mycobacterium tuberculosis (M.tb) is one of the main causes of human death in the world. Bacillus Calmette‐Guérin (BCG) provides limited protection in adolescents and adults. To explore the factors reducing efficacy of BCG vaccine, we assess the impacts of interleukin (IL)‐10 and alarmins S100A8/A9 on T‐cell memory. We found that BCG‐induced IL‐10 inhibited production of S100A8/A9 in human peripheral blood mononuclear cells (PBMCs) and murine splenocytes. S100A9 deficiency inhibited IFN‐γ production by CD4+ T cells in the early phase of BCG immunization and hindered the development of effector memory T helper type 1 (Th1) cells, while IL‐10 deficiency promoted Th1 memory and blocking IL‐10 signaling enhanced Th1 protective recall response against M.tb. IL‐10 inhibited the binding of transcription factor CCAAT enhancer binding protein beta to S100a8/a9 promoter leading to S100A8/A9 reduction. S100A8/A9 heterodimer enhanced the IFN‐γ production via receptor for advanced glycation end products signaling in CD4+ T cells. Our results demonstrate a hurdle to development of Th1 memory after BCG immunization and clarify the mechanism of the regulation of Th1 memory by IL‐10 and S100A8/A9.
Bystander activation of Bordetella pertussis‐induced nasal tissue‐resident memory CD4 T cells confers heterologous immunity to Klebsiella pneumoniae
Authors: Curham Lucy M. , Mannion Jenny M. , Daly Clíodhna M. , Wilk Mieszko M. , Borkner Lisa , Lalor Stephen J. , McLoughlin Rachel M. , Mills Kingston H.G. 
Published: January 2023

AbstractTissue‐resident memory CD4 T (TRM) cells induced by infection with Bordetella pertussis persist in respiratory tissues and confer long‐term protective immunity against reinfection. However, it is not clear how they are maintained in respiratory tissues. Here, we demonstrate that B. pertussis‐specific CD4 TRM cells produce IL‐17A in response to in vitro stimulation with LPS or heat‐killed Klebsiella pneumoniae (HKKP) in the presence of dendritic cells. Furthermore, IL‐17A‐secreting CD4 TRM cells expand in the lung and nasal tissue of B. pertussis convalescent mice following in vivo administration of LPS or HKKP. Bystander activation of CD4 TRM cells was suppressed by anti‐IL‐12p40 but not by anti‐MHCII antibodies. Furthermore, purified respiratory tissue‐resident, but not circulating, CD4 T cells from convalescent mice produced IL‐17A following direct stimulation with IL‐23 and IL‐1β or IL‐18. Intranasal immunization of mice with a whole‐cell pertussis vaccine induced respiratory CD4 TRM cells that were reactivated following stimulation with K. pneumoniae. Furthermore, the nasal pertussis vaccine conferred protective immunity against B. pertussis but also attenuated infection with K. pneumoniae. Our findings demonstrate that CD4 TRM cells induced by respiratory infection or vaccination can undergo bystander activation and confer heterologous immunity to an unrelated respiratory pathogen.
Enantioselective Nickel‐Catalyzed Hydrocyanation of Homostilbenes
Authors: Strache Joss Pepe , Münzer Lukas , Adler Andreas , Blunk Dirk , Schmalz Hans‐Günther 
Published: January 2023

AbstractWe investigated the previously unknown enantioselective Ni‐catalyzed hydrocyanation of 1,3‐diarylpropenes (homostilbenes). For this purpose, a series of (E)‐homostilbenes were prepared by (microwave‐assisted) Pd‐catalyzed coupling of allylic alcohols with aryl‐boronic acids. Employing our established catalyst system formed from Ni(cod)2 and a TADDOL‐derived chiral phosphine‐phosphite ligand and using TMSCN as an in situ source of HCN, the hydrocyanation of various homostilbenes was studied. The synthetic usefulness of the methodology was demonstrated in a short synthesis of the new (allo‐) colchicine analogue 7‐cyano‐11‐methoxy‐colchinol involving an PIDA‐mediated oxidative cyclization of the corresponding hydrocyanation product to set up the 7‐membered ring. The absolute configuration of 2,4‐diphenylbutyronitrile was assigned by comparison of experimental and calculated ECD spectra.
Impact of partial encapsulation on the fire dynamics of an open‐plan compartment with exposed timber ceiling and columns:CodeRed #04
Authors: Kotsovinos Panagiotis , Christensen Eirik G. , Glew Adam , O'Loughlin Eoin , Mitchell Harry , Amin Rikesh , Robert Fabienne , Heidari Mohammad , Barber David , Rein Guillermo , Schulz Judith 
Published: January 2023

AbstractThe use of mass timber in construction is becoming a compelling option when faced with the high carbon footprint of traditional concrete and steel production. However, fire safety standards are yet to evolve to support these designs. Encapsulation is commonly used to protect all, or some, of the timber surfaces and reduce the risks introduced. This paper presents the results fromCodeRed #04, the final experiment of theCodeRedexperimental campaign. This experiment was carried out inside a purpose‐built facility to capture fire dynamics in large compartments with exposed timber.CodeRed #04had identical characteristics toCodeRed #01with the exception that ~50% of the cross‐laminated timber (CLT) ceiling was encapsulated. The experiments were intentionally similar to the traveling fire experiments,x‐ONEandx‐TWO, which had a non‐combustible ceiling to enable a direct comparison. The overall fire dynamics experienced inCodeRed #04, intersect the characteristics observed inCodeRed #01andx‐ONEandx‐TWO.1. InCodeRed #04, there was a delay in the ignition of the CLT ceiling as the CLT directly above the crib was encapsulated. Once the CLT ceiling ignited, the fire spread rapidly throughout the compartment. The peak heat release rate (HRR) was estimated to be approximately 100 MW, a 17% decrease fromCodeRed #01. Following CLT ignition the resulting fire duration, maximum temperatures, and heat fluxes were broadly similar toCodeRed #01. Flame heights of approximately 1.5 m were observed from the windows while flame heights of 2.5–3 m were observed inCodeRed #01. Therefore, flame heights were found to be comparable tox‐TWO.1, though over a greater number of windows, reflecting the greater extent of simultaneous burning within the compartment. The average charring depth of the exposed CLT panels was ~25 mm, which is similar to that measured inCodeRed #01‐suggesting that the fire severity near the ceiling was not strongly impacted by the 50% encapsulation of timber. No charring was observed where the ceiling was encapsulated and loaded service fixings installed through the encapsulation were found to be less likely to fail than when attached directly to the exposed timber. Smoldering was observed after the cessation of flaming and, in a few locations, was observed to progress through the thickness of the CLT panel and continue behind the encapsulation. This illustrates that, while encapsulation can succcessfully prevent flaming, it cannot be completely relied on to avoid smouldering. The findings fromCodeRed #04contribute to the development of evidence‐based fire safety design methodologies for exposed mass timber buildings.