bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of Tildrakizumab Efficacy and Safety in Patients With Active Ankylosing Spondylitis
Authors: Peters Eric , Chou Richard C. , Rozzo Stephen J. , Yao Siu-Long , Fructuoso Ferran José García 
Published: May 2023

Objective
Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody approved to treat moderate to severe plaque psoriasis. This study evaluated the efficacy and safety of tildrakizumab in patients with ankylosing spondylitis (AS).

Methods
In this randomized, double-blind, parallel-group, multinational trial (clinicaltrials.gov NCT02980705), patients with active AS, according to modified New York criteria and Bath Ankylosing Spondylitis Disease Activity Index Score ≥4, were randomized 1:1 to tildrakizumab 200 mg or placebo every 4 weeks until week 24. Thereafter, all patients received tildrakizumab 200 mg every 4 weeks until week 48. The primary outcome was proportion of patients achieving 20% improvement from baseline by Assessment in SpondyloArthritis International Society criteria (ASAS20) at week 24. This outcome was analyzed in subgroups defined by prior treatment experience, weight, age, and sex using the full analysis set. Safety was assessed through treatment-emergent adverse events.

Results
From December 5, 2017–September 3, 2019, 101 patients (76.2% male, 97% White) enrolled and were randomized to treatment. At week 24, the ASAS20 response rate was 74.0% in patients receiving tildrakizumab 200 mg (n = 50) versus 80.4% in placebo-treated patients (n = 51; treatment difference, −6.31%; 95% confidence interval, −22.34 to 9.71; p = 0.44). No difference in treatment effect by subgroups was observed. Tildrakizumab treatment was generally well tolerated, with no unexpected safety findings. The study was terminated after the week 24 interim analysis due to lack of efficacy.

Conclusions
Tildrakizumab treatment was generally well tolerated but did not improve ASAS20 response rate versus placebo in patients with AS.
Utility of 68Ga-FAPI-04 PET/CT in Adenoid Cystic Carcinoma Compared With 18F-FDG PET/CT
Authors: Civan Caner , Isik Emine Goknur , Has Simsek Duygu , Buyukkaya Fikret , Kuyumcu Serkan 
Published: May 2023

Abstract

68Ga–fibroblast activation protein inhibitor (FAPI) PET/CT is an emerging imaging modality with high sensitivity and high tumor-to-background ratio in various cancers including in the head and neck regions. The authors present 2 cases of adenoid cystic carcinoma who underwent 68Ga-FAPI-04 and 18F-FDG PET/CT. Locoregional recurrence has been detected more precisely in the first case with 68Ga-FAPI-04. In the second case, 68Ga-FAPI-04 outperformed 18F-FDG in the number of lesions and demonstrated intense FAP uptake on widespread metastases, which could provide a treatment option as a theranostic concept. These cases highlight that 68Ga-FAPI-04 PET/CT may be useful for detecting local recurrence and metastases and help select patients for radionuclide treatments targeting cancer-associated fibroblasts.
Nasopharyngeal carriage and antimicrobial susceptibility profiles of Streptococcus pneumoniae among children with pneumonia and healthy children in Padang, Indonesia
Authors: Yani Finny Fitry , Julianty Riris Juita , Tafroji Wisnu , Linosefa Linosefa , Ihsan Indra , Masnadi Nice Rachmawati , Safari Dodi 
Published: May 2023

Streptococcus pneumoniae is one of the pathogenic bacteria causing invasive pneumococcal diseases such as pneumonia, sepsis, and meningitis , which are commonly reported in children and adults. In this study, we investigated the nasopharyngeal carriage rates, serotype distribution, and antimicrobial susceptibility profiles of S. pneumoniae among children with pneumonia and healthy children under five years old in Padang, West Sumatra, Indonesia. Nasopharyngeal swabs were collected from 65 hospitalized children with pneumonia in a referral hospital and from 65 healthy children at two Day-care centers from 2018 to 2019. S. pneumoniae was identified by conventional and molecular methods. Antibiotic susceptibility was performed with the disk diffusion method. Out of 130 children, S. pneumoniae strains were carried by 53% and 9.2% in healthy children (35/65) and children with pneumonia (6/65), respectively. Serotype 19F was the most common serotype among the isolated strains (21%) followed by 6C (10%), 14, 34 (7% each), and 1, 23F, 6A, 6B (5% each). Moreover, 55% of the strains (23/42) were covered by the 13-valent pneumococcal conjugate vaccine. Most isolates were susceptible to vancomycin (100%), chloramphenicol (93%), clindamycin (76%), erythromycin (71%), and tetracycline (69%). Serotype 19F was commonly found as a multi-drug resistant strain.
Retrospective Analysis of Equity-Based Optimization for COVID-19 Vaccine Allocation
Authors: Stafford Erin , Dimitrov Dobromir , Ceballos Rachel , Campelia Georgina , Matrajt Laura 
Published: May 2023

AbstractMarginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counter-factual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.
Side-Chain Dynamics of the α1B-Adrenergic Receptor determined by NMR via Methyl Relaxation
Authors: Baumann Christian , Chiang Wan-Chin , Valsecchi Renato , Jurt Simon , Deluigi Mattia , Schuster Matthias , Plückthun Andreas , Zerbe Oliver 
Published: May 2023

AbstractG protein-coupled receptors (GPCRs) are medically important membrane proteins that sample inactive, intermediate, and active conformational states characterized by relatively slow interconversions (∼μs– ms). On a faster timescale (∼ps–ns), the conformational landscape of GPCRs is governed by the rapid dynamics of amino acid side chains. Such dynamics are essential for protein functions such as ligand recognition and allostery. Unfortunately, technical challenges have almost entirely precluded the study of side-chain dynamics for GPCRs. Here, we investigate the rapid side-chain dynamics of a thermostabilized α1B-adrenergic receptor (α1B-AR) as probed by methyl relaxation. We determined order parameters for Ile, Leu, and Val methyl groups in the presence of inverse agonists that bind orthosterically (prazosin, tamsulosin) or allosterically (conopeptide ρ-TIA). Despite the differences in the ligands, the receptor’s overall side-chain dynamics are very similar, including those of the apo form. However, ρ-TIA increases the flexibility of Ile1764x56and possibly of Ile2145x49, adjacent to Pro2155x50of the highly conserved P5x50I3x40F6x44motif crucial for receptor activation, suggesting differences in the mechanisms for orthosteric and allosteric receptor inactivation. Overall, increased Ile side-chain rigidity was found for residues closer to the center of the membrane bilayer, correlating with denser packing and lower protein surface exposure. In contrast to two microbial membrane proteins, in α1B-AR Leu exhibited higher flexibility than Ile side chains on average, correlating with the presence of Leu in less densely packed areas and with higher protein-surface exposure than Ile. Our findings demonstrate the feasibility of studying receptor-wide side-chain dynamics in GPCRs to gain functional insights.
Immune-induced remodelling of mRNA structurome regulates uORF-mediated translation
Authors: Xiang Yezi , Chen Tianyuan , Irving Patrick S. , Weeks Kevin M. , Dong Xinnian 
Published: May 2023

ABSTRACTTo survive stress, eukaryotes selectively translate stress-related transcripts while inhibiting growth-associated protein production. How this translational reprogramming occurs under biotic stress has not been systematically studied. To identify common features shared by transcripts with stress-upregulated translation efficiency (TE-up), we first performed high-resolution ribosome-sequencing inArabidopsisduring pattern-triggered immunity and found that TE-up transcripts are enriched with upstream open reading frames (uORFs). Under non-stress conditions, start codons of these uORFs (uAUGs) have higher-than-background ribosomal association. Upon immune induction, there is an overall downshift in ribosome occupancy at uAUGs, accompanied by enhanced translation of main ORFs (mORFs). Usingin plantanucleotide-resolution mRNA structurome probing, we discovered that this stress-induced switch in translation is mediated by highly structured regions detected downstream of uAUGs in TE-up transcripts. Without stress, these structures are responsible for uORF-mediated inhibition of mORF translation by slowing progression of the translation preinitiation complex to initiate translation from uAUGs, instead of mAUGs. In response to immune induction, uORF-inhibition is alleviated by three Ded1p/DDX3X-homologous RNA helicases which unwind the RNA structures, allowing ribosomes to bypass the inhibitory uORFs and upregulate defence protein production. Conservation of the RNA helicases suggests that mRNA structurome remodelling is a general mechanism for stress-induced translation across kingdoms.
Universal method for the gentle isolation of intact microvessels from frozen tissue: a multiomic investigation into the neurovasculature
Authors: Wakid Marina , Almeida Daniel , Aouabed Zahia , Rahimian Reza , Davoli Maria Antonietta , Yerko Volodymyr , Leonova-Erko Elena , Richard Vincent , Zahedi René , Borchers Christoph , Turecki Gustavo , Mechawar Naguib 
Published: May 2023

AbstractThe neurovascular unit (NVU), comprised of endothelial cells, pericytes, smooth muscle cells, astrocytic endfeet and microglia together with neurons, is paramount for the proper function of the central nervous system. The NVU gatekeeps blood-brain barrier (BBB) properties which, as a system, experiences impairment in several neurological and psychiatric diseases, and contributes to pathogenesis. To better understand function and dysfunction at the NVU, isolation and characterization of the NVU is needed. Here, we describe a singular, standardized protocol to enrich and isolate microvessels from archived snap-frozen human and frozen mouse cerebral cortex using mechanical homogenization and centrifugation-separation that preserves the structural integrity and multicellular composition of microvessel fragments. For the first time, microvessels are isolated from postmortem vmPFC tissue and are comprehensively investigated using both RNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS). Both the transcriptome and proteome are elucidated and compared, demonstrating that the isolated brain microvessel is a robust model for the NVU and can be used to generate highly informative datasets in both physiological and disease contexts.
Cardiomyocyte Targeting Peptide to Deliver Amiodarone
Authors: Zahid Maliha , Weber Beth , Yurko Ray , Islam Kazi , Agrawal Vaishavi , Lopuszynski Jack , Yagi Hisato , Salama Guy 
Published: May 2023

AbstractBackgroundAmiodarone is underutilized due to significant off-target toxicities. We hypothesized that targeted delivery to the heart would lead to lowering of dose by utilizing a cardiomyocyte targeting peptide (CTP), a cell penetrating peptide identified by our prior phage display work.MethodsCTP was synthesized thiolated at the N-terminus, conjugated to amiodarone via Schiff base chemistry, HPLC purified and confirmed with MALDI/TOF. Stability of the conjugate was assessed using serial HPLCs. Guinea pigs (GP) were injected intraperitoneally daily with vehicle (7 days), amiodarone (7 days; 80mg/Kg), CTP-amiodarone (5 days;26.3mg/Kg), or CTP (5 days; 17.8mg/Kg), after which GPs were euthanized, hearts excised, perfused on a Langendorff apparatus with Tyrode’s solution and blebbistatin (5μM) to minimize contractions. Voltage (RH237) and Ca2+-indicator dye (Rhod-2/AM) were injected, fluorescence from the epicardium split and focused on two cameras capturing at 570–595nm for cytosolic Ca2+and 610–750nm wavelengths for voltage. Subsequently, hearts were paced at 250ms with programmed stimulation to measure changes in conduction velocities (CV), action potential duration (APD) and Ca2+transient durations at 90% recovery (CaTD90). mRNA was extracted from all hearts and RNA sequencing performed with results compared to control hearts.ResultsCTP-amiodarone remained stable for up to 21 days at 37°C. At ∼1/15thof the dose of amiodarone, CTP-amiodarone decreased CV in hearts significantly compared to control GPs (0.92±0.05 vs. 1.00±0.03m/s, p=0.0007), equivalent to amiodarone alone (0.87±0.08ms, p=0.0003). Amiodarone increased APD (192±5ms vs. 175±8ms for vehicle, p=0.0025), while CTP-amiodarone decreased it significantly (157±16ms, p=0.0136) similar to CTP alone (155±13ms, p=0.0039). Both amiodarone and CTP-amiodarone significantly decreased calcium transients compared to controls. CTP-amiodarone and CTP decreased CaTD90to an extent greater than amiodarone alone (p<0.001). RNA-seq showed that CTP alone increased the expression of DHPR and SERCA2a, while decreasing expression of proinflammatory genes NF-kappa B, TNF-α, IL-1β, and IL-6.ConclusionsOur data suggests that CTP can deliver amiodarone to cardiomyocytes at ∼1/15ththe total molar dose of amiodarone needed to produce comparable slowing of CVs. The ability of CTP to decrease AP durations and CaTD90may be related to its increase in expression of Ca-handling genes, and merits further study.
Improvisers’ experiences across neurotypes of participating in improv comedy
Authors: Keates Nathan , Beadle-Brown Julie 
Published: May 2023

Purpose
Previous studies have confirmed the potential benefits of participating in theatrical improvisation, including improved mental health, well-being, skills and strategy development. This study aims to explore the experiences of improv (a subset of theatrical improvisation) for autistic, non-autistic, yet neurodivergent and neurotypical people. In particular, it explores whether participants believe that there have been any benefits from participating in improv.

Design/methodology/approach
Twenty adult participants were recruited using snowball sampling. Semi-structured interviews were conducted and analysed using interpretative phenomenological analysis (IPA) and qualitative content analysis (QCA). IPA explored the autistic lived experience during improv participation, while QCA sought to identify the benefits gained.

Findings
Implementing IPA allowed for the benefits of improv to be embedded into autistic lived experience. This was aggregated into two themes: “life beyond improv” and “social worlds negative impact”. Findings from QCA found five themes: “creativity and opportunities: the arts and workplace”; “acceptance, cognitive flexibility and rolling with it”; “interpersonal, social and communication skills and human connection”; “gains in mental health, quality of life and wellbeing”; and for just autistic participants, “‘I've gone full autistic’ (and can learn why neurotypicals are like they are)”.

Originality/value
To the best of the authors’ knowledge, this is a novel study area that has not been investigated previously.
Application maturity evaluation of building steel structure welding robotic technology based on multi-level gray theory
Authors: Yu Hongliang , Peng Zhen , He Zirui , Huang Chun 
Published: May 2023

PurposeThe purpose of this paper is to establish a maturity evaluation model for the application of construction steel structure welding robotics suitable for the actual situation and specific characteristics of engineering projects in China and then to assess the maturity level of the technology in the application of domestic engineering projects more scientifically.Design/methodology/approachThe research follows a qualitative and quantitative analysis method. In the first stage, the structure of the maturity model is constructed and the evaluation index system is designed by using the ideas of the capability maturity model and WSR methodology for reference. In the second stage, the design of the evaluation process and the selection of evaluation methods (analytic hierarchy process method, multi-level gray comprehensive evaluation method). In the third stage, the data are collected and organized (preparation of questionnaires, distribution of questionnaires, questionnaire collection). In the fourth stage, the established maturity evaluation model is used to analyze the data.FindingsThe evaluation model established by using multi-level gray theory can effectively transform various complex indicators into an intuitive maturity level or score status. The conclusion shows that the application maturity of building steel structure welding robot technology in this project is at the development level as a whole. The maturity levels of “WuLi – ShiLi – RenLi” are respectively: development level, development level, between starting level and development level. Comparison of maturity evaluation values of five important factors (from high to low): environmental factors, technical factors, management factors, benefit factors, personnel and group factors.Originality/valueIn this paper, based on the existing research related to construction steel structure welding robot technology, a quantitative and holistic evaluation of the application of construction steel structure welding robot technology in domestic engineering projects is conducted for the first time from a project perspective by designing a maturity evaluation index system and establishing a maturity evaluation model. This research will help the project team to evaluate the application level (maturity) of the welding robot in the actual project, identify the shortcomings and defects of the application of this technology, then improve the weak links pertinently, and finally realize the gradual improvement of the overall application level of welding robot technology for building steel structure.
IT investment and corporate collaborative innovation: the moderating role of the top management team's educational background and absorptive capacity
Authors: Wu Wenqing , Zhang Pianpian , Tsai Sang-Bing 
Published: May 2023

PurposePrevious studies have shown that the application of information technology (IT) can help break through the innovation boundaries of firms and has undoubtedly become a key enabler of collaborative innovation. These studies, however, are mainly based on theoretical analysis and case studies, and little is empirically known about the relationship between IT investments and collaborative innovation. Therefore, the purpose of this study is to empirically explore how firms' IT investments affect the firms' collaborative innovation performance. The authors also examine the moderating roles of the top management team's (TMT's) educational background and absorptive capacity in this relationship.Design/methodology/approachThe authors collected data on 2,097 listed Chinese manufacturing companies and used the ordinary least squares (OLS) method to perform regression analysis. In addition, the authors conducted robustness tests using the propensity score matching (PSM) method and the instrumental variable method.FindingsThe results show that the relationship between IT investments and collaborative innovation is inverted, U-shaped and curvilinear. In addition, the TMT's educational background and absorptive capacity positively moderate the inverted U-shaped relationship between IT investments and collaborative innovation.Originality/valueThe study's findings on the relationship between IT investments and collaborative innovation differ from previous mainstream findings that recognized a positive linear relationship. The authors' findings deepen the understanding of the dual role of IT investments. Moreover, this research helps expand the contingency perspective in IT investments and collaborative innovation research.
Empowering higher education students to monitor their learning progress: opportunities of computerised classification testing
Authors: Ifenthaler Dirk , ŞAHİN Muhittin 
Published: May 2023

Purpose
This study aims to focus on providing a computerized classification testing (CCT) system that can easily be embedded as a self-assessment feature into the existing legacy environment of a higher education institution, empowering students with self-assessments to monitor their learning progress and following strict data protection regulations. The purpose of this study is to investigate the use of two different versions (without dashboard vs with dashboard) of the CCT system during the course of a semester; to examine changes in the intended use and perceived usefulness of two different versions (without dashboard vs with dashboard) of the CCT system; and to compare the self-reported confidence levels of two different versions (without dashboard vs with dashboard) of the CCT system.

Design/methodology/approach
A total of N = 194 students from a higher education institution in the area of economic and business education participated in the study. The participants were provided access to the CCT system as an opportunity to self-assess their domain knowledge in five areas throughout the semester. An algorithm was implemented to classify learners into master and nonmaster. A total of nine metrics were implemented for classifying the performance of learners. Instruments for collecting co-variates included the study interest questionnaire (Cronbach’s a = 0. 90), the achievement motivation inventory (Cronbach’s a = 0. 94), measures focusing on perceived usefulness and demographic data.

Findings
The findings indicate that the students used the CCT system intensively throughout the semester. Students in a cohort with a dashboard available interacted more with the CCT system than students in a cohort without a dashboard. Further, findings showed that students with a dashboard available reported significantly higher confidence levels in the CCT system than participants without a dashboard.

Originality/value
The design of digitally supported learning environments requires valid formative (self-)assessment data to better support the current needs of the learner. While the findings of the current study are limited concerning one study cohort and a limited number of self-assessment areas, the CCT system is being further developed for seamless integration of self-assessment and related feedback to further reveal unforeseen opportunities for future student cohorts.