bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of a Latent Epitope Causing Differential Binding of Antineutrophil Cytoplasmic Antibodies to Proteinase 3
Authors: Casal Moura Marta , Thompson Gwen E. , Nelson Darlene R. , Fussner Lynn A. , Hummel Amber M. , Jenne Dieter E. , Emerling Daniel , Fervenza Fernando C. , Kallenberg Cees G. M. , Langford Carol A. , McCune W. Joseph , Merkel Peter A. , Monach Paul A. , Seo Philip , Spiera Robert F. , St. Clair E. William , Ytterberg Steven R. , Stone John H. , Robinson William H. , Specks Ulrich ,   the WGET and RAVE‐ITN Research Groups
Published: December 2022

ObjectiveProteinase 3 (PR3) is the major antigen for antineutrophil cytoplasmic antibodies (ANCAs) in the systemic autoimmune vasculitis, granulomatosis with polyangiitis (GPA). PR3‐targeting ANCAs (PR3‐ANCAs) recognize different epitopes on PR3. This study was undertaken to study the effect of mutations on PR3 antigenicity.MethodsThe recombinant PR3 variants, iPR3 (clinically used to detect PR3‐ANCAs) and iHm5 (containing 3 point mutations in epitopes 1 and 5 generated for epitope mapping studies) immunoassays and serum samples from patients enrolled in ANCA‐associated vasculitis (AAV) trials were used to screen for differential PR3‐ANCA binding. A patient‐derived monoclonal ANCA 518 (moANCA518) that selectively binds to iHm5 within the mutation‐free epitope 3 and is distant from the point mutations of iHm5 was used as a gauge for remote epitope activation. Selective binding was determined using inhibition experiments.ResultsRather than reduced binding of PR3‐ANCAs to iHm5, we found substantially increased binding of the majority of PR3‐ANCAs to iHm5 compared to iPR3. This differential binding of PR3‐ANCA to iHm5 is similar to the selective moANCA518 binding to iHm5. Binding of iPR3 to monoclonal antibody MCPR3‐2 also induced recognition by moANCA518.ConclusionThe preferential binding of PR3‐ANCAs from patients, such as the selective binding of moANCA518 to iHm5, is conferred by increased antigenicity of epitope 3 on iHm5. This can also be induced on iPR3 when captured by monoclonal antibody MCPR2. This previously unrecognized characteristic of PR3‐ANCA interactions with its target antigen has implications for studying antibody‐mediated autoimmune diseases, understanding variable performance characteristics of immunoassays, and design of potential novel treatment approaches.image
Allosteric and Electrostatic Cooperativity in a Heteroditopic Halogen Bonding Receptor System
Authors: Taylor Andrew J. , Docker Andrew , Beer Paul D. 
Published: December 2022

AbstractA halogen bonding (XB) heteroditopic receptor, consisting of a 1,3‐bis‐iodo‐triazole benzene XB anion binding site covalently appended via a flexible methylene group with two benzo‐15‐crown‐5 (B15C5) cation binding moieties, and its hydrogen bonding receptor analogue, are used to delineate the mechanisms of cooperativity for alkali metal halide ion‐pair recognition. Extensive cation, anion and ion‐pair 1H NMR titration investigations demonstrate the combination of allosteric pre‐organisation, via 1 : 1 stoichiometric intramolecular potassium and rubidium metal cation bis‐B15C5 sandwich complexation, in concert with favourable electrostatics and XB potency, results in a remarkable enhancement of halide anion binding affinity by a factor of at least 700. By contrast, a notably diminished halide anion affinity enhancement factor of just 15 is observed with the corresponding 1 : 1 stoichiometric sodium cation complexed receptor system, where the smaller sized cation singly occupies one B15C5 unit and only an electrostatic contribution to cooperativity is possible. These observations serve to illustrate that allosteric pre‐organisation capability, electrostatic attraction and XB mediated anion recognition are important strategic design features to incorporate in future high‐fidelity heteroditopic ion‐pair receptor development.
Importance of Madden–Julian oscillation phase to the interannual variability of East African rainfall
Authors: Maybee Ben , Ward Neil , Hirons Linda C. , Marsham John H. 
Published: December 2022

AbstractPrecipitation across East Africa shows marked interannual variability. Seasonal forecast skill for the OND short rains is significantly higher than for the MAM long rains, which also exhibit poorly understood decadal variability. On sub‐seasonal time‐scales rainfall is influenced strongly by the phase of the Madden–Julian Oscillation (MJO); here we investigate whether this influence extends to interannual and decadal scales. We show that the number of days that the MJO is active and in phases 1–3 has a greater influence than the mean amplitude of the MJO on interannual long rains variability (ρ = 0.59 for the count of phases 1–3, compared to ρ = 0.40 for amplitude). The frequency of these days is linked to a newly identified gradient in Pacific sea‐surface temperatures (SSTs), whose influence on long rains variability we show is itself mediated by the MJO. We develop a statistical model estimating East African rainfall from MJO state, and show that the influence of the MJO on seasonal rainfall extends to the short rains, and to a lesser extent also into January and February. Our results show the importance of capturing the SST‐MJO phase relationship in models used for predictions of East African rainfall across time‐scales, and motivate investigating this further.
Ein UHPC findet Anwendung in der Tiefseeforschung – Festigkeitskennwerte
Authors: Hering Marcus , Wilhelm Sebastian , Wasemann Heinrich , Bergholz Martin , Beckmann Birgit , Curbach Manfred 
Published: December 2022

AbstractIm Beitrag wird auf die umfangreichen Materialuntersuchungen an einem ultrahochfesten Beton (UHPC) eingegangen, der für die Verwendung in der Tiefsee bestimmt ist. Die durchgeführten Versuche umfassen die Bestimmung des Spannungs‐Verformungs‐Verhaltens bei einaxialer Belastung der Probekörper, die Ermittlung der zweiaxialen Druckfestigkeit des UHPC unter verschiedenen Spannungsverhältnissen sowie die Bestimmung der Zugfestigkeitskennwerte. Auch wurde im Rahmen der Untersuchungen der Elastizitätsmodul experimentell ermittelt. Für die Tests wurden Würfel, Prismen und knochenförmige Probekörper verwendet. Aus den ermittelten Materialkennwerten wurden Umrechnungsfaktoren für die geometrieabhängigen Festigkeiten des Betons ermittelt. Im Rahmen des Beitrags erfolgt zudem ein Vergleich der ermittelten zweiaxialen Druckfestigkeitskennwerte mit weiteren, aus der Literatur bekannten Daten. Hierbei zeigt sich, dass ein UHPC eine ähnliche Festigkeitssteigerung aufweisen kann wie ein Normalbeton.
Time‐resolved fluorescence sensor array for the discrimination of phosphate anions using transition metal dichalcogenide quantum dots and Tb(III)
Authors: Behera Pradipta , Jaiswal Komal , De Mrinmoy 
Published: December 2022

AbstractPhosphate detection has garnered widespread attention due to its biological and environmental impact. Among several optical techniques, time‐resolved fluorescence (TRF) provides a sensitive way for the discrimination of analytes in a complex mixture as it exhibits less interference from the background, therefore providing a high signal‐to‐noise ratio. The sensitization of rare earth metal (REM) ions by semiconducting quantum dots (QDs) can help the former overcome the drawback of low absorption coefficient, therefore allowing exploitation of the additional advantage of the REM, namely the long‐excited state lifetime. Here, we have developed a TRF‐based sensor array consisting of three QDs, i.e. MoS2, WS2 and MoSe2 as energy sensitizers for Tb3+ ions. Different QDs possess variable energy transfer abilities for Tb3+ ions. Therefore, they can be used to discriminate phosphates. It was also observed that CrO42− can competitively bind to Tb3+ and further enhance the efficiency of the sensor array so that it could discriminate six different phosphates at 200 μM concentration in aqueous as well as serum medium with a detection limit of 10 μM in aqueous medium. Therefore, the sensitivity of the TRF‐based sensor array is rarely compromised in a complex mixture, which is advantageous over a fluorescence‐based sensor array.
Membrane‐coated nanoparticles for direct recognition by T cells
Authors: Li Feiran , Li Fanghua , Urie Russell , Bealer Elizabeth , Ruiz Ramon Ocadiz , Saito Eiji , Turan Ali , Yolcu Esma , Shirwan Haval , Shea Lonnie D. 
Published: December 2022

AbstractThe direct modulation of T cell responses is an emerging therapeutic strategy with the potential to modulate undesired immune responses including, autoimmune disease, and allogeneic cells transplantation. We have previously demonstrated that poly(lactide‐co‐glycolide) particles were able to modulate T cell responses indirectly through antigen‐presenting cells (APCs). In this report, we investigated the design of nanoparticles that can directly interact and modulate T cells by coating the membranes from APCs onto nanoparticles to form membrane‐coated nanoparticles (MCNPs). Proteins within the membranes of the APCs, such as Major Histocompatibility Complex class II and co‐stimulatory factors, were effectively transferred to the MCNP. Using alloreactive T cell models, MCNP derived from allogeneic dendritic cells were able to stimulate proliferation, which was not observed with membranes from syngeneic dendritic cells and influenced cytokine secretion. Furthermore, we investigated the engineering of the membranes either on the dendritic cells or postfabrication of MCNP. Engineered membranes could be to promote antigen‐specific responses, to differentially activate T cells, or to directly induce apoptosis. Collectively, MCNPs represent a tunable platform that can directly interact with and modulate T cell responses.
Rational mutagenesis of Thermobifida fusca cutinase to modulate the enzymatic degradation of polyethylene terephthalate
Authors: Mrigwani Arpita , Pitaliya Madhav , Kaur Harman , Kasilingam Bharathraj , Thakur Bhishem , Guptasarma Purnananda 
Published: December 2022

AbstractThermobifida fusca cutinase (TfCut2) is a carboxylesterase (CE) which degrades polyethylene terephthalate (PET) as well as its degradation intermediates [such as oligoethylene terephthalate (OET), or bis‐/mono‐hydroxyethyl terephthalate (BHET/MHET)] into terephthalic acid (TPA). Comparisons of the surfaces of certain CEs (including TfCut2) were combined with docking and molecular dynamics simulations involving 2HE‐(MHET)3, a three‐terephthalate OET, to support the rational design of 22 variants with potential for improved generation of TPA from PET, comprising 15 single mutants (D12L, E47F, G62A, L90A, L90F, H129W, W155F, ΔV164, A173C, H184A, H184S, F209S, F209I, F249A, and F249R), 6 double mutants [H129W/T136S, A173C/A206C, A173C/A210C, G62A/L90F, G62A/F209I, and G62A/F249R], and 1 triple mutant [G62A/F209I/F249R]. Of these, nine displayed no activity, three displayed decreased activity, three displayed comparable activity, and seven displayed increased (~1.3‐ to ~7.2‐fold) activity against solid PET, while all variants displayed activity against BHET. Of the variants that displayed increased activity against PET, four displayed more activity than G62A, the most‐active mutant of TfCut2 known till date. Of these four, three displayed even more activity than LCC (G62A/F209I, G62A/F249R, and G62A/F209I/F249R), a CE known to be ~5‐fold more active than wild‐type TfCut2. These improvements derived from changes in PET binding and not changes in catalytic efficiency.
Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise
Authors: Brícola Rafael S. , Cordeiro André V. , Crisol Barbara M. , Braga Renata R. , de Melo Diego G. , Rocha Matheus B. , Gaspar Rafael C. , Nakandakari Susana C. B. R. , Silva Vagner R. R. , Anaruma Chadi P. , Katashima Carlos K. , Canciglieri Raphael D. S. , Munõz Vitor R. , Pavan Isadora C. B. , Pinto Ana P. , Simabuco Fernando M. , Silva Adelino S. R. da , Moura Leandro P. , Pauli José R. , Cintra Dennys E. , Ropelle Eduardo R. 
Published: December 2022

AbstractDysfunction of the adipose tissue metabolism is considered as a significant hallmark of aging. It has been proposed that α‐β hydrolase domain containing 5 (ABHD5) plays a critical role in the control of lipolysis. However, the role of ABHD5 in the control of lipolysis during aging or exercise is unknown. Here we combined the experimental mouse model with transcriptomic analyzes by using murine and human databases to explore the role of ABHD5 in the adipose tissue during aging and in response to exercise. Transcriptomic data revealed a downregulation of Abhd5 messenger RNA levels in the subcutaneous white adipose tissue (scWAT) over time in individuals from 20 to 69 years old. Aged mice displayed dramatic reduction of ABHD5 protein content and lipolytic‐related proteins in the scWAT. Interestingly, 4 weeks of high‐intensity interval training increased ABHD5 protein level and restored the lipolytic pathway in the scWAT of aged mice. Altogether, our findings demonstrated that aging affects ABHD5 content in the adipose tissue of mice and humans. Conversely, exercise increases ABHD5 activity, recovering the lipolytic activity in aged mice.
Selection of RNA‐Cleaving TNA Enzymes for Cellular Mg2+ Imaging
Authors: Gao Mingmei , Wei Dongying , Chen Siqi , Qin Bohe , Wang Yueyao , Li Zhe , Yu Hanyang 
Published: December 2022

AbstractCatalytic DNA‐based fluorescent sensors have enabled cellular imaging of metal ions such as Mg2+. However, natural DNA is prone to nuclease‐mediated degradation. Here, we report the in vitro selection of threose nucleic acid enzymes (TNAzymes) with RNA endonuclease activities. One such TNAzyme, T17–22, catalyzes a site‐specific RNA cleavage reaction with a kcat of 0.017 min−1 and KM of 675 nM. A fluorescent sensor based on T17–22 responds to an increasing concentration of Mg2+ with a limit of detection at 0.35 mM. This TNAzyme‐based sensor also allows cellular imaging of Mg2+. This work presents the first proof‐of‐concept demonstration of using a TNA catalyst in cellular metal ion imaging.
Malignant lymphoma presenting as bilateral sensorineural hearing loss—A case report
Authors: Raunio Frida , Kelppe Jetta , Hafrén Lena 
Published: December 2022

AbstractBilateral Sensorineural Hearing Loss is a rare disease that is often associated with other complex medical conditions. Primary central nervous system lymphoma is an uncommon and aggressive variant of non‐Hodgkin lymphoma that can mimic many other neurological diseases. Herein, we present a rare case of lymphoma of the CNS as the etiology for progressive SSNHL. We describe a 58‐year‐old male with previous IgG4‐disease presentation who was diagnosed with progressive sensorineural hearing loss. The condition evolved rapidly despite proper, conventional therapy. The patient acquired vestibular symptoms and other cranial nerve deficiencies and he was diagnosed with intracranial lymphoma, mainly in the cerebellar region. This case demonstrates that rare intracranial lymphoma can present initially as sensorineural hearing loss. A higher suspicion for malignancy should be held in mind for patients with a history of IgG4‐related diseases and for patients presenting with progressing bilateral SSNHL that is not responding to therapy.
Spontaneous sublingual hematoma secondary to warfarin therapy—A rare complication
Authors: Adhikari Aakriti , Sharma Shriya , Ghimire Nirmal , Mainali Gaurab , Yadav Sumit Kumar , Rajkarnikar Ruja 
Published: December 2022

AbstractWarfarin is the most commonly prescribed oral anticoagulant in Nepal. It is commonly used for chronic anticoagulation in patients with atrial fibrillation, venous thromboembolism, and artificial heart valves. The major side effect of warfarin is bleeding. Though extremely rare, a sublingual hematoma can lead to life‐threatening complications as it can cause severe airway obstruction. We present a case of a 55‐year‐old female patient who had sublingual hematoma secondary to the use of Warfarin therapy. In addition to the discontinuation of warfarin, she was managed conservatively without any surgical intervention. Early diagnosis, timely discontinuation of the drug, and application of appropriate medical treatment are of utmost importance for reducing morbidity and mortality due to bleeding and airway compromise.
Uterine rupture in the third trimester of a pregnancy subsequent to a cesarean section by transverse uterine fundal incision: A case report and literature review
Authors: Koshimizu Kei , Kakogawa Jun , Murata Shuko , Suzuki Masato , Suzuki Takashi , Masaoka Naoki 
Published: December 2022

AbstractCesarean section via a transverse uterine fundal incision is performed in patients with placenta previa to reduce blood loss. We describe a case of uterine rupture in a pregnant woman who previously underwent a cesarean section and recovered from cardiac arrest by multidisciplinary management.
Bayesian Genetic Colocalization Test of Two Traits Using coloc
Authors: Rasooly Danielle , Peloso Gina M. , Giambartolomei Claudia 
Published: December 2022

AbstractGenetic colocalization is an approach for determining whether a genetic variant at a particular locus is shared across multiple phenotypes. Genome‐wide association studies (GWAS) have successfully mapped genetic variants associated with thousands of complex traits and diseases. However, a large proportion of GWAS signals fall in non‐coding regions of the genome, making functional interpretation a challenge. Colocalization relies on a Bayesian framework that can integrate summary statistics, for example those derived from GWAS and expression quantitative trait loci (eQTL) mapping, to assess whether two or more independent association signals at a region of interest are consistent with a shared causal variant. The results from a colocalization analysis may be used to evaluate putative causal relationships between omics‐based molecular measurements and a complex disease, and can generate hypotheses that may be followed up by tailored experiments. In this article, we present an easy and straightforward protocol for conducting a Bayesian test for colocalization of two traits using the ‘coloc’ package in R with summary‐level results derived from GWAS and eQTL studies. We also provide general guidelines that can assist in the interpretation of findings generated from colocalization analyses. © 2022 Wiley Periodicals LLC.Basic Protocol: Performing a genetic colocalization analysis using the ‘coloc’ package in R and summary‐level dataSupport Protocol: Installing the ‘coloc’ R package
Atypical Anorexia Nervosa is not atypical at all! Commentary on Walsh et al. (2022)
Authors: Golden Neville H. 
Published: December 2022

AbstractThe introduction of atypical anorexia nervosa (atypAN) as a new diagnosis in DSM‐5 has advanced the field by expanding awareness that individuals of all weights can have an eating disorder. However, many clinical and research questions remain, particularly pertaining to whether atypAN and anorexia nervosa (AN) are different conditions or the same condition across the weight spectrum. In this issue of the journal, Walsh et al. describe the results of their systematic review demonstrating that the level of eating disorder‐specific psychopathology is significantly higher among individuals with atypAN than among controls, and as high or higher than among individuals with AN. Levels of noneating disorder psychopathology are similar. Individuals with atypAN experience many of the medical complications associated with AN but at a lower frequency. The finding that the clinical features of atypAN are not substantially different from AN supports the possibility that atypAN and AN are the same condition. Further research on epidemiology, genetics, treatment, course and outcome is required to determine whether atypAN and AN are the same or different, but there is a need to update and refine existing terminology and diagnostic classification.
Initial experience with transcatheter tricuspid valve repair in patients with cardiac amyloidosis
Authors: Hoerbrand Isabel A. , Volz Martin J. , Aus dem Siepen Fabian , Aurich Matthias , Schlegel Philipp , Geis Nicolas A. , Hegenbart Ute , Konstandin Mathias H. , Frey Norbert , Raake Philip W. 
Published: December 2022

AbstractAimsWildtype transthyretin amyloid cardiomyopathy is an under‐recognized cause of heart failure in elderly patients. Transcatheter tricuspid valve repair is a newly emerging therapeutic option for severe tricuspid regurgitation (TR). We present first insights into safety and possible benefits of this procedure in patients with cardiac amyloidosis.Methods and resultsEight patients with cardiac non‐hereditary (wildtype) transthyretin (ATTRwt) amyloidosis and severe to torrential TR, undergoing successful transcatheter tricuspid valve repair, were included in the analysis and compared to a control group of 21 patients without cardiac amyloidosis. All patients presented with an advanced stage of amyloid cardiomyopathy. Primary endpoint was reduction in TR at 3 months follow‐up. Secondary endpoints were feasibility, safety, hospitalization or death, clinical improvement, cardiac biomarkers, and structural and functional right heart parameter obtained by echocardiography. Transcatheter tricuspid valve repair resulted in a significant reduction of TR (IV to II, P = 0.008) in all eight patients with cardiac amyloidosis (100%). Device success (amyloidosis 75% vs. control group 86%, P = 0.597) and overall probability of hospitalization or death (amyloidosis 13% vs. control group 25%, P = 0.646) were similar compared with those in the control group at 3 months follow‐up. Transcatheter tricuspid valve repair led to an improvement of New York Heart Association functional class (P = 0.031) and 6 min walking distance (from 313 ± 118 to 337 ± 106, P = 0.012). TR reduction in amyloidosis patients was less extensive compared with that in control group (TR‐reduction 1.6 ± 0.3, P = 0.008 vs. control group 2.3 ± 0.3, P < 0.0001). Furthermore, these patients showed no significant improvement of structural right heart parameters.ConclusionsTranscatheter tricuspid valve repair is a safe and feasible new treatment option in patients with amyloid cardiomyopathy and has the potential to improve TR‐grade and clinical status. However, the benefit appears to be less pronounced compared with patients without cardiac amyloidosis.
A Series of Low‐Coordinate Iron Selenido Complexes: Reactivity of a Linear Iron(I) Silylamide towards Selenium
Authors: Schneider Christian , Ivlev Sergei , Werncke C. Gunnar 
Published: December 2022

AbstractA variety of different low‐coordinate iron selenide complexes is reported. These are obtained by reaction of the linear iron(I) silylamide K{18c6}[Fe(N(Dipp)SiMe3)2] (Dipp=2,6‐diisopropylphenyl) with red selenium. Careful adjustment of the reaction conditions results in the formation of unique low‐coordinate selenido iron complexes, namely a monoselenide bridged [2Fe−1Se]2+ complex, as well as mononuclear iron per‐ and triselenides. Further, C−H bond activation of one of the silylamide ligands by a putative terminal iron monoselenide is observed.