bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Renal Impairment on the Pharmacokinetics of Gefapixant, a P2X3 Receptor Antagonist
Authors: Nussbaum Jesse C. , Hussain Azher , Min K. Chris , Marbury Thomas C. , Lasseter Kenneth , Stoch S. Aubrey , Iwamoto Marian 
Published: June 2022

AbstractGefapixant, a P2X3 receptor antagonist, has demonstrated efficacy in patients with refractory or unexplained chronic cough. We investigated the effect of renal impairment (RI) on the pharmacokinetics (PK) of gefapixant 50 mg in an open‐label, single‐dose study enrolling participants with moderate (n = 6) or severe (n = 6) RI, end‐stage renal disease (ESRD; n = 6) under hemodialysis (HD) and non‐HD conditions, and healthy matched controls (n = 6). Serial plasma and urine samples for gefapixant concentrations were collected at selected time points over 72 and 48 hours after dosing, respectively. Linear regression analysis predicted a 1.87‐, 2.79‐, and 3.76‐fold higher exposure (area under the plasma concentration–time curve) for participants with mild, moderate, and severe RI, respectively, than that for healthy matched control participants. Categorical analysis exhibited a 2.98‐, 4.43‐, and 4.74‐fold higher exposure for participants with moderate RI, severe RI, and ESRD, respectively, than that for healthy matched control participants. Apparent oral clearance and renal clearance was lower in participants with various degrees of RI, by 66% to 90%, compared with healthy matched control participants, explaining the increased gefapixant exposure with increasing degrees of renal impairment. Gefapixant area under the plasma concentration–time curve and maximum plasma concentration decreased by ≈25% under HD conditions compared to non‐HD conditions. Single‐dose administration of gefapixant was generally well tolerated in this study. The data from this trial informed the enrollment of phase 3 clinical trials that evaluated the efficacy and safety of gefapixant in >2000 participants with refractory or unexplained chronic cough. Those efficacy and safety data, combined with analysis of population pharmacokinetics from across the entire development program, will be used to evaluate the magnitude of the renal impairment effect in the refractory or unexplained chronic cough population and to determine any dose adjustment recommendations.
An Open‐Label, Single‐Arm, Pilot Intervention Study to Assess the Efficacy and Safety of Apixaban in Heparin‐Induced Thrombocytopenia
Authors: Farasatinasab Maryam , Balouchzehi Saeedeh , Moghaddam Omid Moradi , Ansarinejad Nafiseh , Mohammadi Mahmonir , Nasiripour Somayyeh 
Published: June 2022

AbstractHeparin‐induced thrombocytopenia (HIT) is a serious adverse drug reaction due to its related risk of life‐ and limb‐threatening thrombosis. Apixaban is a direct factor Xa inhibitor that may be intended as an ideal alternative for the management of HIT. In this open‐label, single‐arm, pilot intervention study, the efficacy and safety of apixaban were evaluated in 30 patients aged >18 years with clinically suspected HIT (4Ts score ≥4 points). Patients with mechanical heart valves, chronic kidney disease, hepatic impairment, and active bleeding were excluded. In all patients with inclusion criteria, heparin or enoxaparin was discontinued and apixaban was started. The dose of apixaban for HIT suspected patients was defined on the basis of the reason for anticoagulant therapy. End points included confirmed thrombosis, mortality, and adverse treatment‐related events. After apixaban therapy, platelet counts normalized in all patients; none of the 30 subjects developed new, progressive, or recurrent thrombosis; and only 1 of 30 patients developed a hemorrhagic event. Five patients (16.7%) died, but the reason for death was not linked to thrombosis, hemorrhage, or adverse effects of apixaban. Along with the available emerging data, our results propose that apixaban could be a safe and effective drug for the management of suspected HIT in clinically stable patients.
The influence of interpersonal relationships on brand‐related behaviors for gifted brands
Authors: Carnevale Marina , Kachersky Luke 
Published: June 2022

AbstractThe present work studies a novel perspective on gift‐giving research by examining the effect of the giver–recipient relationship on the recipient–brand relationship. A study examining gift exchanges in real‐life relationships and two laboratory experiments demonstrate that the effect of the recipient's relationship satisfaction with the gift giver on self‐brand connections and, consequently, on brand‐related behaviors is conditional on the durability of the gift. The findings are robust to manipulating the durability of the same product category and using durable and nondurable categories of the same (actual or fictitious) brand. This research offers important implications for managers who position their brands as desirable gifts.
The forewing of a black cicada Cryptotympana atrata (Hemiptera, Homoptera: Cicadidae): Microscopic structures and mechanical properties
Authors: Li Qian , Ji Aihong , Shen Huan , Han Qingfei , Qin Guodong 
Published: June 2022

AbstractInsects in nature flap their wings to generate lift force and driving torque to adjust their attitude and control stability. An insect wing is a biomaterial composed of flexible membranes and tough veins. In this paper, we study the microscopic structures and mechanical properties of the forewing of the black cicada, Cryptotympana atrata. The thickness of the wing membranes and the diameter of veins varied from the wing root to the tip. The thickness of the wing membranes ranged from 6.0 to 29.9 μm, and the diameter of the wing veins decreased in a gradient from the wing root to the tip, demonstrating that the forewing of the black cicada is a nonuniform biomaterial. The elastic modulus of the membrane near the wing root ranged from 4.45 to 5.03 GPa, which is comparable to that of some industrial membranes. The microstructure of the wing vein exhibited a hollow tubular structure with flocculent structure inside. The “fresh” sample stored more water than the “dry” sample, resulting in a significant difference in the elastic modulus between the fresh and dried veins. The different membrane thicknesses and elastic moduli of the wing veins near the root and tip resulted in varied degrees of deformation on both sides of the flexion line of the forewing during twisting. The measurements of the forewing of the cicada may serve as a guide for selecting airfoil materials for the bionic flapping‐wing aircraft and promote the design and manufacture of more durable bionic wings in the future.Research Highlights
The distribution of the wing vein diameter and the wing membrane thickness indicated that the forewing of Cryptotympana atrata is composed of heterogeneous materials.
The wing membrane and the outer wall of the wing vein are the layered structure with multilayer fibers, which has a great significance for improving the ability of the forewing to sustain aerodynamic loads.
The elastic modulus of the wing membrane near the wing root is in the range of 4.45–5.03 GPa, which is comparable to that of membranes manufactured by industries. This is a suitable reference for selecting materials for making bionic aircraft wings.
We proved that the elastic moduli of the “fresh” and “dry” wing veins differ greatly compared with those of the wing membrane. Because the wing vein microstructure exhibits an internal hollow tubular structure with flocculent structure inside, the “fresh” sample stores more water than the “dry” sample.
The wing membrane near the wing root is thicker and reinforced by the main wing vein with a high elastic modulus. This renders the region near the wing root difficult to deform. The membrane far from the wing root is thinner and the elastic modulus of the nearby wing veins is smaller, making them more flexible.
A multi‐omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells
Authors: Hinzman Charles P. , Singh Baldev , Bansal Shivani , Li Yaoxiang , Iliuk Anton , Girgis Michael , Herremans Kelly M. , Trevino Jose G. , Singh Vijay K. , Banerjee Partha P. , Cheema Amrita K. 
Published: June 2022

AbstractAlthough cancer‐derived extracellular vesicles (cEVs) are thought to play a pivotal role in promoting cancer progression events, their precise effect on neighbouring normal cells is unknown. In this study, we investigated the impact of pancreatic cancer ductal adenocarcinoma (PDAC) derived EVs on recipient non‐tumourigenic pancreatic normal epithelial cells upon internalization. We demonstrate that cEVs are readily internalized and induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in treated normal pancreatic epithelial cells within 24 h. We further show that PDAC cEVs increase cell proliferation, migration, and invasion and that these changes are regulated at least in part, by the UPR mediator DDIT3. Subsequently, these cells release several inflammatory cytokines. Leveraging a layered multi‐omics approach, we analysed EV cargo from a panel of six PDAC and two normal pancreas cell lines, using multiple EV isolation methods. We found that cEVs were enriched for an array of biomolecules which can induce or regulate ER stress and the UPR, including palmitic acid, sphingomyelins, metabolic regulators of tRNA charging and proteins which regulate trafficking and degradation. We further show that palmitic acid, at doses relevant to those found in cEVs, is sufficient to induce ER stress in normal pancreas cells. These results suggest that cEV cargo packaging may be designed to disseminate proliferative and invasive characteristics upon internalization by distant recipient normal cells, hitherto unreported. This study is among the first to highlight a major role for PDAC cEVs to induce stress in treated normal pancreas cells that may modulate a systemic response leading to altered phenotypes. These findings highlight the importance of EVs in mediating disease aetiology and open potential areas of investigation toward understanding the role of cEV lipids in promoting cell transformation in the surrounding microenvironment.
Exomeres and supermeres: Monolithic or diverse?
Authors: Tosar Juan Pablo , Cayota Alfonso , Witwer Kenneth 
Published: June 2022

AbstractExtracellular vesicles (EVs), including exosomes and microvesicles, are far from being the only RNA‐containing extracellular particles (EPs). Recently, new 35‐nm‐sized EPs were discovered by asymmetric‐flow field‐flow fractionation and termed ‘exomeres’. Purification of exomeres was later performed by differential ultracentrifugation as well. More recently, the supernatant of the high‐speed ultracentrifugation used to collect exomeres was further centrifuged to collect a new class of EP, termed ‘supermeres’. Supermeres contain high quantities of extracellular RNA and are enriched in miR‐1246. They are also replete in disease biomarkers and can induce metabolic and adaptive changes in recipient cells. Here, we reanalysed proteomic and transcriptomic data obtained in this exciting study to obtain further insights into the molecular composition of exomeres and supermeres. We found that the top‐ranking RNAs in supermeres correspond to the footprints of extracellular protein complexes. These complexes protect fragments of the small nuclear RNA U2 and the 28S rRNA from extracellular ribonucleases (exRNases). We suggest that intracellular nanoparticles such as the U2 ribonucleoprotein, ribosomes and LGALS3BP ring‐like decamers are released into the extracellular space. These heterogeneous EPs might be further processed by exRNases and co‐isolate by ultracentrifugation with other components of exomeres and supermeres. We look forward to continuing progress in defining exRNA carriers, bridging process definitions with molecular composition and function.
Efficacy of intraductal placement of nonflared fully‐covered metal stent for refractory perihilar benign biliary strictures: A multicenter prospective study with long‐term observation
Authors: Matsumoto Kazuyuki , Kato Hironari , Fujii Masakuni , Ueki Toru , Saragai Yosuke , Tsugeno Hirofumi , Mannami Tomohiko , Okada Hiroyuki 
Published: June 2022

AbstractBackgroundEndoscopic fully‐covered self‐expandable metal stents (FCSEMSs) are used to treat benign biliary strictures (BBSs); however, treatment for perihilar BBSs is technically challenging. The aim of this study was to evaluate the usefulness of an unflared FCSEMS designed for intraductal placement in patients with refractory perihilar BBS.MethodsTwenty‐two consecutive patients with perihilar BBS unresolved by endoscopic plastic stent placement at 13 tertiary medical centers were prospectively enrolled. The FCSEMS was placed above the papilla and removed after 4 months. The primary outcome was stricture resolution at 4 months, and the secondary outcomes were technical success, stent removal, adverse events, and recurrence.ResultsThe technical success rate of intraductal FCSEMS placement was 100%, and plastic stent placement at contralateral or side branch was performed in 86% of patients. The rate of successful stent removal at 4 months was 100%, and stricture resolution was observed in 91% of patients. Stent migration or stent‐induced de novo stricture did not occur in any patient. The stricture recurrence rate was 16%, and the median (interquartile range) follow‐up duration was 2.8 (1.6‐3.3) years.ConclusionsIntraductal placement of unflared FCSEMS is effective treatment for refractory perihilar BBS.
Efficacy and safety of direct peroral cholangioscopy using a new multibending ultra‐slim endoscope for the management of biliary diseases
Authors: Lee Yun Nah , Moon Jong Ho , Lee Tae Hoon , Yoo Hae Won , Yang Jae Kook , Cha Sang‐Woo , Cho Young Deok , Park Sang‐Heum 
Published: June 2022

AbstractBackground/PurposeCompared with currently available duodenoscopy‐assisted systems, direct peroral cholangioscopy (DPOC) using an ultra‐slim endoscope is limited by technical difficulties. The multibending (MB) ultra‐slim endoscope was introduced as a dedicated cholangioscope for DPOC to challenge the technical problem. We retrospectively analyzed the clinical utility of DPOC using an MB endoscope with free‐hand insertion into the bile duct in patients with biliary diseases.MethodsA total of 145 patients who underwent DPOC using an MB endoscope were analyzed. The primary outcome was the technical success rate of DPOC using the free‐hand insertion of the MB endoscope. The secondary outcomes were the technical success rates of DPOC‐guided diagnostic and therapeutic interventions, the diagnostic accuracy of DPOC‐guided target biopsy, and adverse events related to DPOC.ResultsFree‐hand biliary insertion of a MB endoscope for DPOC was technically successful in 133 patients (91.7%). DPOC‐guided target biopsy was successful in 36 of 38 patients (94.7%) and had a diagnostic accuracy of 91.7% (95% confidence interval, 82.6‐100). Sixty‐nine therapeutic interventions were performed; technical success was achieved in 65 (94.2%). No severe adverse events were observed.ConclusionsThe MB ultra‐slim endoscope was technically effective to perform a DPOC including various diagnosis and therapeutic interventions without device assistance. MB endoscope is considered to contribute to expanding a role of DPOC in diagnosis and treatment of diverse biliary tract diseases.
IgM+ and IgM– memory B cells represent heterogeneous populations capable of producing class-switched antibodies and germinal center B cells upon rechallenge withP. yoelii
Authors: Brown Susie L , Bauer Jonathan J , Lee Juhyung , Ntirandekura Enatha , Stumhofer Jason S 
Published: June 2022

AbstractMemory B cells (MBCs) are essential for maintaining long-term humoral immunity to infectious organisms, including Plasmodium. MBCs are a heterogeneous population whose function can be dictated by isotype or expression of particular surface proteins. Here, aided by antigen-specific B-cell tetramers, MBC populations were evaluated to discern their phenotype and function in response to infection with a nonlethal strain of P. yoelii. Infection of mice with P. yoelii 17X resulted in 2 predominant MBC populations: somatically hypermutated isotype-switched (IgM–) and IgM+ MBCs that coexpressed CD73 and CD80 that produced antigen-specific antibodies in response to secondary infection. Rechallenge experiments indicated that IgG-producing cells dominated the recall response over the induction of IgM-secreting cells, with both populations expanding with similar timing during the secondary response. Furthermore, using ZsGreen1 expression as a surrogate for activation-induced cytidine deaminase expression alongside CD73 and CD80 coexpression, ZsGreen1+CD73+CD80+IgM+, and IgM– MBCs gave rise to plasmablasts that secreted Ag-specific Abs after adoptive transfer and infection with P. yoelii. Moreover, ZsGreen1+CD73+CD80+ IgM+ and IgM– MBCs could differentiate into B cells with a germinal center phenotype after adoptive transfer. A third population of B cells (ZsGreen1–CD73–CD80–IgM–) that is apparent after infection responded poorly to reactivation in vitro and in vivo, indicating that these cells do not represent a canonical population of MBCs. Together these data indicated that MBC function is not defined by immunoglobulin isotype, nor does coexpression of key surface markers limit the potential fate of MBCs after recall.
An Ex‐vivo Model Examining Acoustics and Aerodynamic Effects Following Medialization With and Without Arytenoid Adduction
Authors: Maddox Alexandra , Oren Liran , Farbos de Luzan Charles , Howell Rebecca , Gutmark Ephraim , Khosla Sid 
Published: June 2022

Objectives/HypothesisQuantify differences in acoustics and intraglottal flow fields between Thyroplasty Type 1 (TT1) with and without arytenoid adduction (AA) using excised canine larynx model.Study DesignBasic science experiments using excised larynges.MethodsSurgical procedures were implemented in eight excised canine larynges. Acoustics and intraglottal flow measurements were taken at low and high subglottal pressures in each experimental setup.ResultsIn all larynges, vocal efficiency (VE) and cepstrum peak prominence (CPP) were higher, and the mean phonatory flow rate was lower in TT1 with AA than without AA. The glottal asymmetry is reduced with AA and promotes the formation of stronger vortices in the glottal flow during the closing phase of the vibrating folds.ConclusionsFindings suggest a clear acoustic and aerodynamic benefit to the addition of AA when performing TT1. It shows significant improvement in CPP, translating to decreased breathiness and dysphonia and increased VE, leading to easier and more sustainable phonation. Stronger intraglottal vortices are known to be correlated with the loudness of voice produced by phonation.Level of EvidenceN/A Laryngoscope, 133:621–627, 2023
How and when Narcissism and faith in humanity drive sustainable consumption
Authors: Bowen Karen T. , Musarra Giuseppe , Ou Yi‐Chun 
Published: June 2022

AbstractThe aim of this study is to examine how and when narcissism and faith in humanity simultaneously influence product reuse. Despite its critical role in promoting sustainability, scholars have paid scant attention to product reuse as a reliable aspect of sustainable consumer behavior. Moreover, research on personality traits as drivers of sustainable consumption has mostly focused on the Big Five personality traits. We posit that the effects of consumers' narcissism and faith in humanity on product reuse are explained by social exclusion and are conditional on subjective norms. We test our hypotheses using two experiments and three cross‐sectional surveys. We find that while narcissism has a negative effect on product reuse, faith in humanity has a positive effect on product reuse. We also observe that social exclusion mediates the effects of narcissism and faith in humanity, and that subjective norms positively moderate the relationships between narcissism and product reuse. This study highlights the importance of product reuse as a key indicator of sustainable consumption and offers novel insights into the how and when consumers engage in product reuse.
Older adults' decisions on smart home systems: Better put an age tag on it!
Authors: Tipaldi Petra , Natter Martin 
Published: June 2022

AbstractAddressing the demands of our aging society, technologies such as smart home systems enhance older adults' independence and enable them to live longer at home. Yet, older adults tend to avoid, delegate, or defer decisions, and smart home systems are rarely used by individuals over the age of 65. Drawing on research on choice overload and age labels, we investigate across four studies how the presentation of smart home systems can influence the decision‐making process of older adults ages 65+ by mitigating choice complexity and, consequently, choice avoidance. We argue that age‐framing of complex systems makes the choice options easier to process for older adults than does price‐framing, the current market standard. We find that age‐framing positively affects the rate of choice, and we identify reduced choice complexity as the underlying process. Our research further demonstrates that family members, as important co‐deciders, evaluate decisions made on age‐framed alternatives more positively, thus making it easier for older adults to justify their decisions. We thus contribute to research on the decision‐making of older adults in general and on age labels in particular, and we identify important practical implications for providers of high investment products for older adults.
Cernunnos defect in an Iranian patient with T− B+NK+ severe combined immunodeficiency: A case report and review of the literature
Authors: Jamee Mahnaz , Khakbazan Fard Nasrin , Fallah Shahrzad , Golchehre Zahra , Fallahi Mazdak , Shamsian Bibi Shahin , Sharafian Samin , Chavoshzadeh Zahra 
Published: June 2022

AbstractBackgroundDefective Cernunnos gene in nonhomologous end‐joining (NHEJ) pathway of the DNA repair is responsible for radiosensitive severe combined immunodeficiency (SCID). Herein, presented a new patient with Cernunnos deficiency and summarized the clinical, immunological, and molecular features of reported patients in the literature.CaseThe patient was a 6‐month‐old female born to consanguineous parents. She presented with long‐lasting fever, diarrhea, poor feeding, and restlessness. She had suffered from recurrent fever of unknown origin and multiple episodes of oral candidiasis. In the physical examination, microcephaly, failure to thrive, oral candidiasis, pustular rash on fingers, and perianal ulcers, but no dysmorphic feature were observed. The immunologic workup revealed lymphopenia, neutropenia, normocytic anemia, low T‐ but normal B‐ and natural killer (NK)‐ cells, low immunoglobulin (Ig)G, and normal IgA, IgM, and IgE. The T‐cell receptor excision circle (TREC) was low and the lymphocyte transformation test (LTT) was abnormal to mitogens and antigens. She was diagnosed with T− B+ NK+ SCID and improved by intravenous immunoglobulin along with antimicrobials. A homozygous splice site variant, c.390 + 1G > T, at the intron 3 of the NHEJ1, was identified and the diagnosis of Cernunnos deficiency was established. However, while a candidate for hematopoietic stem cell transplantation, she developed sepsis and died at 11 months of age.ConclusionsCernunnos deficiency should be considered as a differential diagnosis in patients with microcephaly, growth retardation, recurrent infections, T‐cell defects, and hypogammaglobulinemia. The normal B‐cell level in the index patient is an unexpected finding in Cernunnos deficiency which requires further evaluation.