bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining Donor-derived Cell-free DNA Fraction and Quantity to Detect Kidney Transplant Rejection Using Molecular Diagnoses and Histology as Confirmation
Authors: Halloran Philip F. , Reeve Jeff , Madill-Thomsen Katelynn S. , Kaur Navchetan , Ahmed Ebad , Cantos Carlos , Al Haj Baddar Nour , Demko Zachary , Liang Nathan , Swenerton Ryan K. , Zimmermann Bernhard G. , Van Hummelen Paul , Prewett Adam , Rabinowitz Matthew , Tabriziani Hossein , Gauthier Phil , Billings Paul ,   the Trifecta Investigators*
Published: June 2022

Background.

Donor-derived cell-free DNA (dd-cfDNA) fraction and quantity have both been shown to be associated with allograft rejection. The present study compared the relative predictive power of each of these variables to the combination of the two, and developed an algorithm incorporating both variables to detect active rejection in renal allograft biopsies.

Methods.

The first 426 sequential indication biopsy samples collected from the Trifecta study (ClinicalTrials.gov # NCT04239703) with microarray-derived gene expression and dd-cfDNA results were included. After exclusions to simulate intended clinical use, 367 samples were analyzed. Biopsies were assessed using the molecular microscope diagnostic system and histology (Banff 2019). Logistic regression analysis examined whether combining dd-cfDNA fraction and quantity adds predictive value to either alone. The first 149 sequential samples were used to develop a two-threshold algorithm and the next 218 to validate the algorithm.

Results.

In regression, the combination of dd-cfDNA fraction and quantity was found to be significantly more predictive than either variable alone (P = 0.009 and P < 0.0001). In the test set, the area under the receiver operating characteristic curve of the two-variable system was 0.88, and performance of the two-threshold algorithm showed a sensitivity of 83.1% and specificity of 81.0% for molecular diagnoses and a sensitivity of 73.5% and specificity of 80.8% for histology diagnoses.

Conclusions.

This prospective, biopsy-matched, multisite dd-cfDNA study in kidney transplant patients found that the combination of dd-cfDNA fraction and quantity was more powerful than either dd-cfDNA fraction or quantity alone and validated a novel two-threshold algorithm incorporating both variables.
Notoginsenoside R1 alleviates spinal cord injury by inhibiting oxidative stress, neuronal apoptosis, and inflammation via activating the nuclear factor erythroid 2 related factor 2/heme oxygenase-1 signaling pathway
Authors: Luo Hongbo , Bao Zhangli , Zhou Mingjian , Chen Yuxin , Huang Zhaoxi
Published: June 2022

The secondary injury plays a vital role in the development of spinal cord injury (SCI), which is characterized by the occurrence of oxidative stress, neuronal apoptosis, and inflammatory response. Notoginsenoside R1 (NGR1) has been involved in the modulation of antioxidative stress and anti-inflammatory response. However, its roles in SCI-induced injury are still unknown. We explored the therapeutic effect of NGR1 and its underlying mechanism after SCI by using behavioral, biochemical, and immunohistochemical techniques. The administration of NGR1 after SCI enhanced the neurological function, and mitigated tissue damage and motor neuron loss than those in SCI + vehicle group. Meanwhile, significantly increased expression of Nrf2 protein and HO-1 protein was found in the SCI + NGR1 group compared with those in the SCI + vehicle group. In addition, the inhibitory effects of oxidative stress, apoptotic neuron ratio, and neuronal inflammation in the SCI + NGR1 group can be partially reversed when the Nrf2/HO-1 signaling pathway was inhibited by ML385. Our results indicate that the administration of NGR1 can attenuate oxidative stress, neuronal apoptosis, and inflammation by activating the Nrf2/HO-1 signaling pathway after SCI, thereby improving neurological function.
Duncan Dowson. 31 August 1928—6 January 2020
Authors: Bradley Derek
Published: June 2022

After completion of his PhD studies, under Derman Christopherson at Leeds, Duncan Dowson spent most of his life researching in tribology and writing its history. Building on the early studies of Osborne Reynolds and later Russian scientists, he made outstanding contributions to the field of elastohydrodynamic lubrication. This is the science of lubrication in which account is also taken of the deformation of the bearing material. An important parameter is the ratio of the elastrohydrodynamic lubricant film thickness to the bounding surface roughness. This is coupled to considerations of surface deformation and wear. In engines, an important consideration is the use of piston sealing rings to contain the hot combustion gases. Similar lubricant film and wear analyses are applicable to artificial hip and knee joints. A fruitful collaboration developed with the Rheumatism Research Unit at Leeds. and a novel pendulum machine was developed to measure the friction in artificial joints. At that time, low friction in hip joints was achieved with stainless steel components, with high molecular weight polytetrafluoroethylene (PTFE) for the cup. Wear rates at the interfaces were excessive and alternatives continue to be sought, including metal-on-metal joints. This has led to extensive experimental studies of the wear in such joints by Duncan and his colleagues, revealing dependencies upon the metal, its surface roughness and any added lubricants. These experiments included the compatibility of different metals in metal-on-metal joints, their interconnected fluid film roughness and wear rate.
Preclinical efficacy of bacosides-lauric acid nano-herbal formulation in comparison to rivastigmine for treatment of Alzheimer’s disease
Authors: Kumar Ashish , Goyal Kritika , Pal Muneesh , Upadhyay Prabhat , Gupta Sarika , Koul Veena , Konar Arpita
Published: June 2022

Despite decades of rigorous scientific endeavors for Alzheimer’s disease (AD) drug development, massive failures in clinical trials is continuously posing healthcare and societal burden. Currently recommended single targeted drugs including rivastigmine with limited bioavailability can alleviate AD symptoms only for a limited period of time but unable to reverse the disease progression. Recent evidences consider poly-pharmacological and multi-targeted agents aiming at amyloid and tau burden, neuroinflammation, neuroprotection and cognitive enhancement as potential treatment options. In this regard, bioactive herbal compounds with holistic action and minimal adversities have gained prominence, though lacunae in their scientific validation and limited bio-permeability to cross BBB represent major hurdles. Previously, we showed that lactoferrin conjugated PEG-S-S-PLA-PCL-OH efficaciously delivered herbal compounds to brain and such nano-herbal formulation of bacosides-lauric acid (BAN-LAN) attenuated neuronal damages induced by scopolamine in vitro. Here, we tested the preclinical potential of BAN-LAN in reversal of AD pathologies in 5XFAD transgenic mice. Our nano-herbal formulation substantially reduced amyloid burden by clearing Aβ plaques in the hippocampus of 5XFAD mice and also attenuated aβ42 induced alterations in AD associated gene expression in hippocampal neurons in vitro. It showed neuroprotection by rescuing neuronal damage and promoting neurogenesis in the hippocampus of AD transgenic mice. Anti-neuroinflammatory properties were also exhibited by the formulation as evident from inhibition of hippocampal astrocytic and microglial activation in 5XFAD mice. BAN-LAN showed cognitive efficacy by restoring memory impairment in AD transgenic mice and effects were more pronounced than unconjugated natural form and rivastigmine. These findings suggest that BAN-LAN may serve as a promising therapeutic agent for AD with better brain penetration and targeting multiple AD pathways.
Spontaneous electroretinogram signals to screen people with early risk factors for diabetic retinopathy
Authors: Noguez Imm Ramsés , Muñoz-Benitez Julio , Medina Diego , Barcenas Everardo , Molero-Castillo Guillermo , Reyes-Ortega Pamela , Hughes-Cano Jorge Armando , Medrano-Gracia Leticia , Miranda-Anaya Manuel , Rojas-Piloni Gerardo , Quiroz-Mercado Hugo , Hernández-Zimbrón Luis Fernando , Fajardo-Cruz Elisa Denisse , Ferreyra-Severo Ezequiel , García-Franco Renata , López-Star Ellery , García-Roa Marlon , Lansingh Van Charles , Thébault Stéphanie C.
Published: June 2022

Given the ever-increasing prevalence of type 2 diabetes and obesity, the pressure on global healthcare is expected to be colossal, especially in terms of blindness. Electroretinogram (ERG) has long been perceived as a first-use technique for diagnosing eye diseases, but existing methods are insufficient to screen early risk factors of diabetic retinopathy (DR). Here, we introduce non-evoked ERG as a simple, fast modality to record spontaneous activity, from which we developed a single random forest-based model that predicts disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome. Classification performance was validated using a dataset from an independent eye center. Our algorithm can be coupled with different ERG sensors, including ones working with portative, non-mydriatic devices. Principal component and discriminant analysis suggest slow spontaneous ERG frequencies as main discriminators for our predictive model. Our study will facilitate the implementation of interventions for the prevention of overweight and obesity by providing a robust, quantitative, and non-invasive identification and follow-up approach, which should ultimately reduce DR incidence.
IMMUNE GENE REGULATION IN THE GUT DURING METAMORPHOSIS IN TWO HOLO- VERSUS A HEMIMETABOLOUS INSECT
Authors: Manthey Christin , Johnston Paul R. , Rolff Jens
Published: June 2022

During complete metamorphosis, holometabolous insects remodel their entire anatomy, including the gut and must control their microbiota to avoid infectious disease. High activity of antimicrobial peptides and proteins in the gut during metamorphosis has been best described in several Lepidoptera. The immune system of the dipteran Drosophila melanogaster also controls the number of bacteria during metamorphosis. However, little is known about the regulation of immune genes during the larval–adult moult in Hemimetabola which undergo less drastic metamorphic changes. Different patterns of immune effector expression during metamorphosis were shown in a study comparing the lepidopteran Galleria mellonela and the orthopteran Gryllus bimaculatus, where G. mellonella showed a strong up-regulation of antimicrobial peptides in the gut at the larval-pupal moult but not G. bimaculatus. Whether these findings reflect general patterns within holometabolous versus hemimetabolous insects remains unclear. Using RNAseq, we compare the expression of immune effector genes in the gut during metamorphosis in two holometabolous (Calliphora vicina and Tenebrio molitor) and a hemimetabolous insect (Pyrrhocoris apterus). We found high read count abundances of differentially expressed immune effectors in the gut at the larval-pupal moult in C. vicina and T. molitor; no such high abundances were observed at the larval-adult moult in P. apterus. Our findings confirm that only complete metamorphosis elicits a prophylactic immune response as an adaptive response in holometabolous insects, which controls the microbiota during gut replacement.
A study of hyperelastic continuum models for isotropic athermal fibrous networks
Authors: Song Dawei , Oberai Assad A , Janmey Paul A
Published: June 2022

Many biological materials contain fibrous protein networks as their main structural components. Understanding the mechanical properties of such networks is important for creating biomimicking materials for cell and tissue engineering, and for developing novel tools for detecting and diagnosing disease. In this work, we develop continuum models for isotropic, athermal fibrous networks by combining a single-fiber model that describes the axial response of individual fibers, with network models that assemble individual fiber properties into overall network behavior. In particular, we consider four different network models, including the affine, three-chain, eight-chain, and micro-sphere models, which employ different assumptions about network structure and kinematics. We systematically investigate the ability of these models to describe the mechanical response of athermal collagen and fibrin networks by comparing model predictions with experimental data. We test how each model captures network behavior under three different loading conditions: uniaxial tension, simple shear, and combined tension and shear. We find that the affine and three-chain models can accurately describe both the axial and shear behavior, whereas the eight-chain and micro-sphere models fail to capture the shear response, leading to an unphysical zero shear moduli at infinitesimal strains. Our study is the first to systematically investigate the applicability of popular network models for describing the macroscopic behavior of athermal fibrous networks, offering insights for selecting efficient models that can be used for large-scale, finite-element simulations of athermal networks.
A knowledge-based view of emerging market firm internationalization: the case of the Indian IT industry
Authors: Ray Pradeep , Ray Sangeeta , Kumar Vikas
Published: June 2022

Purpose

Contemporary frameworks in the resource-based view (RBV) of the firm observe that the proprietary firm-specific assets of multinational companies (MNCs) from developed economies give them competitive advantage in international markets. However, the question “how do emerging market firms (EMFs) achieve accelerated internationalisation in knowledge based industries – despite not possessing proprietary assets and lacking critical elements of innovation eco-systems, institutions and infrastructure” has yet to be addressed. This paper aims to adopt a knowledge-based view (KBV) of the firm, identifying knowledge, both inside and outside of the firm, as a critical element for the internationalization of EMFs.

Design/methodology/approach

This research entailed deductive econometric analyses using panel data analysis from 925 firm-year observations, which tested our predictions on capabilities that contribute to the internationalization of EMFs from the IT industry in India.

Findings

The findings of the authors’ panel data analysis reveal that the capacity to internationalize is predicated by knowledge leverage in three principal domains: absorptive capacity, tacit knowledge and knowledge-codification. This study shows internationalization is driven by higher-order capabilities of EMFs that draw on the absorptive capacity of individuals and collectives as a dynamic capability to serve international clients worldwide.

Research limitations/implications

This study highlights that the process by which EMFs gain competence is different to the Western MNCs insofar as the extent to which EMFs have to stretch their efforts of learning from clients.

Practical implications

For practitioners, the findings of this research are a useful guide to understand that EMFs need to make strategic investments to understand the idiosyncrasies of a variety of clients’ needs and operating environments to dynamically adapt, document the learning and leverage the tacit knowledge.

Social implications

This study captures the innate ability of entrepreneurs in emerging economies to unlock their potential in human capital for globalizing operations and targeting new market segments in the industry. This can directly benefit in uplifting the income level of millions in relatively underdeveloped countries and bringing about much-needed equity in the level of income in the society.

Originality/value

The value of this study lies in its novel and contemporary insight on how EMFs leapfrog in a fast-changing technology space. What distinguishes the work from the static framework in literature is that EMFs learning is dynamic, and happens in an interactive mode, alongside clients in close proximity. This study captures the innate ability of entrepreneurs to unlock the potential of human capital in emerging economies for globalizing operations.
Interagency and global coalitions in combating illicit financial flows: the case of Nigeria
Authors: Ebire Kolawole , Daniels Patrick Olasehinde
Published: June 2022

Purpose

This paper aims to assess the roles of agencies in combating illicit financial flows (IFFs) in Nigeria. Specifically, this paper explores the roles of the major anti-corruption agencies – the Economic and Financial Crimes Commission (EFCC) and Independent Corrupt Practices and other Related Offences Commission (ICPC) – in curbing IFFs in Nigeria. This paper reviews the various activities and achievements of these agencies in combating IFFs and concludes that in spite of the effort made by these anti-graft agencies, Nigeria still ranks top among African countries suffering from IFFs. Therefore, this study recommends a need for a collective and coordinated strategy by authorities worldwide to address the difficulties posed by financial crimes.

Design/methodology/approach

This study reviews the roles of anti-graft agencies in combating IFFs in Nigeria. Specifically, this study explores the roles of EFCC and ICPC in combating IFFs.

Findings

This study concludes that in spite of the effort made by Nigeria’s anti-graft agencies, IFFs have continued to increase thereby impeding the effort to achieve Sustainable Development Goal 16.4 – reduce IFFs.

Originality/value

This study contributes to the existing body of knowledge by exploring Nigeria's major anti-graft agencies and their effort in curbing IFFs in Nigeria.
Does financial awareness increase the acceptance rate for financial inclusion? An empirical examination in the era of digital transformation
Authors: Al-Okaily Manaf , Alqudah Hamza , Al-Qudah Anas Ali , Al-Qadi Naim S. , Elrehail Hamzah , Al-Okaily Aws
Published: June 2022

Purpose

Despite extensive discussion of this topic in the life and financial transactions of people, there is a lack of empirical evidence related to challenges and opportunities of digital financial inclusion sustainability in the existing literature. Accordingly, this study aims at investigating the factors that influence the diffusion rate of digital financial services.

Design/methodology/approach

In this study, the authors propose an integrated model by synthesising the extended Unified Theory of Acceptance and Use of Technology 2 (UTAUT2) with the perceived security and perceived privacy as independent variables, as well as the financial awareness as the moderator variable. The survey was distributed to the potential users of digital financial services rather than the actual users. A total of 270 responses were analysed by a quantitative method of Partial Least Squares-Structural Equation Modelling (PLS-SEM).

Findings

The results indicated the significant role of the postulated hypotheses that behavioural intention to use digital financial services platforms is significantly and positively influenced by the subjective norm, performance expectancy, price value, perceived security and perceived privacy, whilst the financial awareness was found to moderate some specified relationships.

Originality/value

There are few studies on this topic for the Arabian context. The information presented in this article can be useful for professionals and researchers, and further, implications of the study are discussed.
Networking the commons: creative commons project creators funding patterns in crowdfunding
Authors: Wang Rong , Lu Li , Fulk Janet
Published: June 2022

Purpose

Guided by the collective action theory, signaling theory and social identity approach, this study examines backing behavior by individuals who have created projects under CC licenses. Two motivational mechanisms were examined: (1) identification via common interests in the CC space; (2) resource signaling by other users via their diverse project creation experience, funding or commenting activity.

Design/methodology/approach

Data were collected from Kickstarter.com. Exponential random graph modeling was used to examine how the two reviewed mechanisms influence the tie formation probability between Creative Commons (CC) project creators and other creators. The analysis was conducted on two subnetworks: one with ties between CC creators; and one with ties from CC creators to non-CC creators.

Findings

The study found that CC creators exhibit distinct backing patterns when considering funding other CC creators compared to non-CC users. When considering funding their peer CC creators, CC identity can help them allocate and support perceived in-group members; when considering funding non-CC creators, shared common interests in competitive project categories potentially triggers a competition mindset and makes them hold back when they see potential rivals.

Originality/value

This study makes three contributions. First, it draws from multiple theoretical frameworks to investigate unique motivations when crowdfunders take on dual roles of creators and funders and offered implications on how to manage competition and collaboration simultaneously. Second, with network analysis our study not only identifies multiple motivators at work for collective action, but also demonstrates their differential effects in crowdfunding. Third, the integration of multiple theoretical frameworks allows opportunities for theory building.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/OIR-05-2020-0166.
Bioactive polysaccharides and oligosaccharides from garlic (Allium sativum L.): Production, physicochemical and biological properties, and structure–function relationships
Authors: Qiu Zhichang , Qiao Yiteng , Zhang Bin , Sun‐Waterhouse Dongxiao , Zheng Zhenjia
Published: June 2022

Garlic is a common food, and many of its biological functions are attributed to its components including functional carbohydrates. Garlic polysaccharides and oligosaccharides as main components are understudied but have future value due to the growing demand for bioactive polysaccharides/oligosaccharides from natural sources. Garlic polysaccharides have molecular weights of 1 × 103 to 2 × 106 Da, containing small amounts of pectins and fructooligosaccharides and large amounts of inulin‐type fructans ((2→1)‐linked β‐d‐Fruf backbones alone or with attached (2→6)‐linked β‐d‐Fruf branched chains). This article provides a detailed review of research progress and identifies knowledge gaps in extraction, production, composition, molecular characteristics, structural features, physicochemical properties, bioactivities, and structure–function relationships of garlic polysaccharides/oligosaccharides. Whether the extraction processes, synthesis approaches, and modification methods established for other non‐garlic polysaccharides are also effective for garlic polysaccharides/oligosaccharides (to preserve their desired molecular structures and bioactivities) requires verification. The metabolic processes of ingested garlic polysaccharides/oligosaccharides (as food ingredients/dietary supplements), their modes of action in healthy humans or populations with chronic conditions, and molecular/chain organization–bioactivity relationships remain unclear. Future research directions related to garlic polysaccharides/oligosaccharides are discussed.
Using gridCoal to assess whether standard population genetic theory holds in the presence of spatio‐temporal heterogeneity in population size
Authors: Szép Enikő , Trubenová Barbora , Csilléry Katalin
Published: June 2022

Spatially explicit population genetic models have long been developed, yet have rarely been used to test hypotheses about the spatial distribution of genetic diversity or the genetic divergence between populations. Here, we use spatially explicit coalescence simulations to explore the properties of the island and the two‐dimensional stepping stone models under a wide range of scenarios with spatio‐temporal variation in deme size. We avoid the simulation of genetic data, using the fact that under the studied models, summary statistics of genetic diversity and divergence can be approximated from coalescence times. We perform the simulations using gridCoal, a flexible spatial wrapper for the software msprime (Kelleher et al., 2016, Theoretical Population Biology, 95, 13) developed herein. In gridCoal, deme sizes can change arbitrarily across space and time, as well as migration rates between individual demes. We identify different factors that can cause a deviation from theoretical expectations, such as the simulation time in comparison to the effective deme size and the spatio‐temporal autocorrelation across the grid. Our results highlight that FST, a measure of the strength of population structure, principally depends on recent demography, which makes it robust to temporal variation in deme size. In contrast, the amount of genetic diversity is dependent on the distant past when Ne is large, therefore longer run times are needed to estimate Ne than FST. Finally, we illustrate the use of gridCoal on a real‐world example, the range expansion of silver fir (Abies alba Mill.) since the last glacial maximum, using different degrees of spatio‐temporal variation in deme size.
Impact of end‐of‐century climate change on priority non‐timber forest product species across tropical Africa
Authors: Amoussou Biowa Eldys N. , Idohou Rodrigue , Glèlè Kakaï Romain , Dauby Gilles , Couvreur Thomas L. P.
Published: June 2022

Plant species providing Non‐Timber Forest Products (NTFP) are economically important across Africa. How this heterogeneous and understudied resource will respond to ongoing climate change remains understudied. Here, we modelled the impact of end‐of‐the‐century climate change on the distribution of 40 NTFP plant species distributed across tropical Africa. Occurrence data were extracted from a taxonomically verified database and three different ecological niche modelling algorithms were used. Species distributions were modelled under two end‐of‐century (2085) climate change models (RCP4.5 and RCP8.5) and two dispersal scenarios (limited and expanded). We show that for the 40 NTFP plant species studied here, different responses are modelled with some species gaining in suitable habitats (47.5%–65% under RCP4.5), whereas others will lose in suitable habitats (35%–52.5% under RCP4.5). Nevertheless, we also show that our results vary between the different methods used, such as modelling algorithms, dispersal scenarios and general circulation models. Overall, our results suggest that the response of NTFP species to climate change depends on their distribution, ecology and dispersal ability.
Comparison of the initial ovarian response, the synchrony of oestrus and ovulation and chronic stress response after administration of 100 or 250 μg of GnRH to randomly cycling Bos indicus cattle
Authors: Abdallah M , Joone C , Edwards S , Das S , Cavalieri J
Published: June 2022

Objective

This study investigated the effects of administering saline, 100 or 250 μg of gonadotrophin releasing hormone (GnRH) on ovarian response, synchrony of oestrus and ovulation and chronic stress response in Bos indicus cattle.

Design

Randomised control.

Methods

Animals were either left untreated (n = 20) or on day 0 treated with an intravaginal progesterone releasing device and either saline (n = 24), 100 μg (n = 35), or 250 (n = 35) μg of GnRH, intramuscular (IM). Blood was sampled 1.4 h after administration of treatment to monitor concentrations of luteinising hormone (LH) and P4 in serum and again 5 days later. On day 5 intravaginal P4 releasing device were removed, cloprostenol was administered IM and again 8 h later. Oestrus and ovulation were then monitored with ultrasonography for 6.5 days. Hair was clipped on day 55 for analysis of hair cortisol concentrations (HCC).

Results

No significant differences were found between Saline and GnRH treatments in the odds of inducing a new corpus luteum (CL) and the synchrony of oestrus or ovulation. HCC did not differ significantly between treatments. Mean concentrations of LH in serum on day 0 were less in the Saline compared to 100 and 250 μg GnRH treatments but did not differ between different doses of GnRH.

Conclusion

Mean concentrations of LH and the odds of inducing a new CL were not increased after administering 250 μg compared to 100 μg of GnRH. Animal handling events in the study did not influence HCC. Further research is needed to better optimise responses to GnRH in B. indicus cattle.
Lithium replacement dose recommendations using Monte Carlo simulations
Authors: Methaneethorn Janthima , Mannie Zola , Bell Erica , Malhi Gin S.
Published: June 2022

Objectives

Missed medication doses are a common clinical problem, and cause consternation when prescribing lithium because its plasma levels must be kept within a narrow therapeutic window. Therefore, this study set out to determine the potential impact of missed lithium doses on its pharmacokinetics, and to explore the optimal compensatory dosing scheme. This is difficult to determine clinically and in research because of ethical constraints and therefore we modelled the effects using simulations.

Methods

Monte Carlo simulations were used to simulate lithium concentrations under different missed dose scenarios. For patients with normal renal function, the optimal replacement dosing scheme was selected based on the lowest percentage of deviation from the full adherence scenario. However, for patients with renal impairment the appropriate dosing schedule was selected based on the lowest number of simulated concentrations above the upper range of 1.2 mEq/L.

Results

The impact of a missed lithium dose depended on its daily dose. The higher the daily dose, the higher the deviation from full adherence. In patients with normal renal function, replacement with a regular dose was most appropriate. But in patients with renal impairment, replacement with a partial dose appeared to be most suitable.

Conclusions

This study has enabled insights into the optimal suitable lithium replacement dosing schemes for patients with normal renal function and renal impairment. These proposed schemes can be used cautiously in clinical practice in conjunction with clinician judgment and can also be used as a basis for future clinical research.
Evaluation of chimeric antigen receptor of humanized rabbit‐derived T cell receptor‐like antibody
Authors: Nakamura Tomoko , Kobayashi Eiji , Hamana Hiroshi , Hayakawa Yoshihiro , Muraguchi Atsushi , Hayashi Atsushi , Ozawa Tatsuhiko , Kishi Hiroyuki
Published: June 2022

T‐cell receptor (TCR)‐like Abs that specifically recognize antigenic peptides presented on MHC molecules have been developed for next‐generation cancer immunotherapy. Recently, we reported a rapid and efficient method to generate TCR‐like Abs using a rabbit system. We humanized previously generated rabbit‐derived TCR‐like Abs reacting Epstein–Barr virus peptide (BRLF1p, TYPVLEEMF) in the context of HLA‐A24 molecules, produced chimeric antigen receptor (CAR)‐T cells, and evaluated their antitumor effects using in vitro and in vivo tumor models. Humanization of the rabbit‐derived TCR‐like Abs using the complementarity‐determining region grafting technology maintained their specificity and affinity. We prepared a second‐generation CAR using single‐chain variable fragment of the humanized TCR‐like Abs and then transduced them into human T cells. The CAR‐T cells specifically recognized BRLF1p/MHC molecules and lysed the target cells in an antigen‐specific manner in vitro. They also demonstrated antitumor activity in a mouse xenograft model. We report the generation of CAR‐T cells using humanized rabbit‐derived TCR‐like Abs. Together with our established and efficient generation procedure for TCR‐like Abs using rabbits, our platform for the clinical application of humanized rabbit‐derived TCR‐like Abs to CAR‐T cells will help improve next‐generation cancer immunotherapy.
Community health worker intervention to improve tooth brushing in young children: Results from a cluster randomized controlled trial
Authors: Martin Molly A. , Avenetti David , Lee Helen H. , Nordgren Rachel , Berbaum Michael L. , Edomwande Yuwa , Cui Liyong , Sandoval Anna
Published: June 2022

Objectives

Coordinated Oral health Promotion (CO‐OP) Chicago is a cluster randomized controlled trial testing the efficacy of a community health worker (CHW) intervention to improve tooth brushing in low‐income children.

Methods

Four hundred twenty children under 3 years old (mean 21.5 months) were recruited from 20 sites in or near Chicago, IL. Children were identified mainly as Black race (41.9%) or Hispanic ethnicity (53.8%) and most (85.2%) had Medicaid. Intervention families were offered four CHW home visits over 1 year. Brushing frequency was self‐reported. Plaque score was determined from images collected in homes using disclosing solution. Analyses used GEE logistic models with variable selection at p < .05.

Results

At enrolment, 45.0% of families reported twice a day or more child brushing frequency, and child plaque scores were poor (mean of 1.9, SD: 0.6). Data were obtained from 87.1% of children at 6 months and 86.2% at 12 months. In the CHW intervention arm (10 sites, N = 211), 23.7% received 4 visits, 12.8% 3 visits, 21.3% 2 visits, 23.2% 1 visit and 19% no visits from CHWs. No intervention effect was seen for brushing frequency or plaque score. Child brushing frequency improvement over time was associated with a range of child and caregiver factors. The only factor associated with a change in plaque score over time was parent involvement in brushing.

Conclusions

Oral‐health‐specific CHW services were not associated with improved brushing behaviours in these young children. However, caregiver involvement with brushing supported more quality brushing. More robust interventions are needed to support families during this critical developmental period.
Nowhere to go: Housing pathways of college students with foster care and homelessness experience
Authors: Skobba Kim , Moorman Diann , Meyers David , White Kenneth , Tiller Lori
Published: June 2022

This study builds on previous research to understand longer term housing experiences in late adolescence and early adulthood for vulnerable college students. Using a biographical, qualitative method, we study high school and college housing and family circumstances for 27 students with homelessness or foster care experience enrolled in 4‐year colleges in Georgia. We identified three different housing pathway types in high school—family homelessness, unaccompanied youth and foster care. Housing instability and frequent moves were common in high school among all housing pathway types. In college, students who were able to find low or no‐cost housing and those who identified a foster care pathway in high school achieved greater housing stability. Others students experienced a continuation of housing instability that began in high school. Additional funding to cover the cost of on‐campus housing would likely contribute to increased stability. Additional strategies, such as rental assistance programmes tailored for college students, may be needed to address housing instability for vulnerable college students. More research on the unmet housing needs and the consequences of housing instability during college for homeless and foster youth is needed to further a housing policy agenda that focuses on practical solutions.
A phase IB/IIA study of remestemcel‐L, an allogeneic bone marrow‐derived mesenchymal stem cell product, for the treatment of medically refractory ulcerative colitis: an interim analysis
Authors: Lightner Amy L. , Dadgar Neda , Matyas Caroline , Elliott Kavita , Fulmer Clifton , Khaitan Neha , Ream Justin , Nachand Douglas , Steele Scott R.
Published: June 2022

Aim

There have been no studies into the direct injection of mesenchymal stem cells (MSCs) for luminal ulcerative colitis (UC). Our aim was to investigate the efficacy of MSCs delivered locally via endoscopic delivery, as is done in the setting of perianal disease, to treat the local site of inflammation directly.

Method

A phase IB/IIA randomized control clinical trial of remestemcel‐L, an ex vivo expanded allogeneic bone marrow‐derived MSC product, at a dose of 150 million MSCs versus placebo (2:1 fashion) delivered via direct injection using a 23‐gauge sclerotherapy needle at the time of colonoscopy was designed to assess the safety and efficacy of endoscopic delivery of MSCs for UC. The main outcome measures were adverse events, Mayo score and Mayo endoscopic severity score at 2 weeks, 6 weeks and 3 months post‐MSC delivery.

Results

Six patients were enrolled and treated; four received MSCs and two placebo. All had been on prior anti‐tumour necrosis factor or anti‐integrin therapy. There were no adverse events related to MSCs. In the treatment group (n = 4), the Mayo endoscopic severity score decreased in all patients by 2 weeks after MSC delivery. At 3 months, all patients were extremely satisfied or satisfied with their MSC treatment based on the inflammatory bowel disease patient‐reported treatment impact (IBD‐PRTI), and treatment response was described as excellent or good in all patients. In the control group (n = 2), the Mayo endoscopic severity score did not increase as a result of being off alternative therapy. At 3 months, patients were dissatisfied according to the IBD‐PRTI, and treatment response was poor or unchanged.

Conclusion

MSCs may offer a safe therapeutic option for the treatment of medically refractory UC. Early data suggest improved clinical and endoscopic scores by 2 weeks after MSC delivery.
Ten‐year follow up of previously traumatized immature permanent incisors sustaining second and third traumatic injuries after revascularization treatment: Case reports
Authors: Cehreli Zafer C. , Unverdi Gizem Erbas , Serdar Eymirli Pinar
Published: June 2022

The long‐term prognosis of previously traumatized immature permanent teeth treated with guided endodontic repair is well documented, but little is known about how these teeth respond to further traumatic injury after treatment. This case report presents the 10‐year clinical and radiographic findings of two patients with traumatized maxillary incisors who underwent guided endodontic repair treatment and sustained two further traumatic injuries. Three crown‐fractured maxillary central incisors with pulp necrosis were treated with a protocol that used 2.5% NaOCl irrigation, 3–4 weeks medication with calcium hydroxide or ciprofloxacin‐metronidazole paste, induction of apical bleeding, and coronal sealing with mineral trioxide aggregate. One tooth sustained subluxation and a crown fracture after 20 months and 7 years, respectively. Two other teeth had a luxation injury at 9 months and subluxation 6.5 years after the repair treatment. One subluxated and one luxated tooth remained free of symptoms for 10 years with radiographic evidence of progressive root canal calcification, while the other luxated incisor required root canal treatment after 7.5 years. Although teeth treated with the so‐called “regenerative” endodontic techniques do not possess true pulp tissue, the reparative tissue may respond to traumatic injuries in a similar manner to teeth with normal pulps.
Improving diversity in study participation: Patient perspectives on barriers, racial differences and the role of communities
Authors: Shea Lisa , Pesa Jacqueline , Geonnotti Gabrielle , Powell Valerie , Kahn Caryl , Peters Wesley
Published: June 2022

Introduction

The lack of racial/ethnic diversity in research potentially limits the generalizability of findings to a broader population, highlighting the need for greater diversity and inclusion in clinical research. Qualitative research (i.e., focus groups) was conducted to identify (i) the potential motivators and barriers to study participation across different races and ethnicities; (ii) preferred delivery of education and information to support healthcare decision‐making and the role of the community.

Methods

Patient focus groups were conducted with 26 participants from the sponsor's Patient Engagement Research Councils selected through subjective sampling. Recruitment prioritized adequate representation across different race/ethnic groups. Participation was voluntary and participants underwent a confidential interview process before selection. Narrative analysis was used to identify themes and draw insights from interactions. Experienced research specialists identified emerging concepts, and these were tested against new observations. The frequency of each concept was examined to understand its importance.

Results

Based on self‐selected race/ethnicity, participants were divided into five focus groups (Groups: African American/Black: 2; Hispanic/Latino, Asian American, and white: 1 each) and were asked to share their experiences/opinions regarding the stated objectives. Barriers to study participation included: limited awareness of opportunities to participate in research, fears about changes in standard therapy, breaking cultural norms/stigma, religion‐related concerns and mistrust of clinical research. Participants identified the importance of transparency by pharmaceutical companies and other entities to build trust and partnership and cited key roles that communities can play. The perceptions of the African American group regarding diversity/inclusion in research studies appeared to be different from other groups; a lack of trust in healthcare providers, concerns about historical instances of research abuse and the importance of prayer were cited.

Conclusion

This study provided insights into barriers to study participation, and also highlighted the need for pharmaceutical companies and other entities to authentically engage in strategies that build trust within communities to enhance recruitment among diverse populations.

Patient or Public Contribution

The data collected in the present study was provided by the participants in the focus groups.
A large‐scale field experiment on occupational gender segregation and hiring discrimination
Authors: Adamovic Mladen , Leibbrandt Andreas
Published: June 2022

We analyze the relationship between occupational gender composition and gender discrimination in recruitment and investigate whether there is hiring discrimination against men in female‐dominated occupations. We do this with a large‐scale field experiment where we submitted more than 12,000 job applications for 12 occupations in Australia, varying the gender of the applicants. Men received around 50% more callbacks than women in male‐dominated occupations, while they received over 40% fewer callbacks in female‐dominated occupations.
Pectinolytic arsenal of Colletotrichum lindemuthianum and other fungi with different lifestyles
Authors: da Silva Leandro Lopes , Morgan Túlio , Garcia Ediones Amaro , Rosa Rafael Oliveira , Mendes Tiago Antônio de Oliveira , de Queiroz Marisa Vieira
Published: June 2022

Aim

To identify and analyse genes that encode pectinases in the genome of the fungus Colletotrichum lindemuthianum, evaluate the expression of these genes, and compare putative pectinases found in C. lindemuthianum with pectinases produced by other fungi and oomycetes with different lifestyles.

Methods and Results

Genes encoding pectinases in the genome of C. lindemuthianum were identified and analysed. The expression of these genes was analysed. Pectinases from C. lindemuthianum were compared with pectinases from other fungi that have different lifestyles, and the pectinase activity in some of these fungi was quantified. Fifty-eight genes encoding pectinases were identified in C. lindemuthianum. At least six types of enzymes involved in pectin degradation were identified, with pectate lyases and polygalacturonases being the most abundant. Twenty-seven genes encoding pectinases were differentially expressed at some point in C. lindemuthianum during their interactions with their host. For each type of pectinase, there were at least three isoenzyme groups. The number of pectinases present in fungi with different lifestyles seemed to be related more to the lifestyle than to the taxonomic relationship between them. Only phytopathogenic fungi showed pectate lyase activity.

Conclusions

The collective results demonstrate the pectinolytic arsenal of C. lindemuthianum, with many and diverse genes encoding pectinases more than that found in other phytopathogens, which suggests that at least part of these pectinases must be important for the pathogenicity of the fungus C. lindemuthianum.

Significance and Impact of the Study

Knowledge of these pectinases could further the understanding of the importance of this broad pectinolytic arsenal in the common bean infection and could be exploited for biotechnological purposes.
Focusing on fundamentals of care in an ICU setting during a pandemic
Authors: Amaral Nely , Merkley Jane , Ronald Kara , Farquharson Carolyn , Ginty Leanne , Heng Diana , Jeffs Lianne
Published: June 2022

Aims

This manuscript aims to describe one acute care hospital's ICU journey during the COVID‐19 pandemic and how fundamental care was central to the implementation of team‐based models of care.

Background

Over the course of the COVID‐19 pandemic, team‐based and alternative models of care are being employed to manage and address global shortages and surge capacity. Employing these alternate models of care required attention to ensure fundamental care needs of patients were being met.

Design/Method

The following paper describes an ICU's journey of focusing on the delivery of the fundamentals of care through the implementation of team‐based models of care to address the surge in patient care demands experienced in response to our global pandemic.

Conclusions

The implementation of an evidence‐informed approach to optimizing models of care and staffing in the ICU amid the evolving COVID‐19 waves in one acute‐care hospital is provided. This local approach focused on meeting patients' fundamental care needs throughout the necessary introduction of team‐based care models and staffing changes and drew from evolving evidence, the ILC Fundamentals of Care Framework, and regulatory guidance.
Occult arterial bleeding associated with cardiac device implantation
Authors: Demirtas Abdullah O. , Sanhueza Eduardo , Singh Sheldon M.
Published: June 2022

Introduction

The appearance of hematomas or hemorrhages after the implantation of a cardiac implantable electronic device (CIEDs) is a well‐known early complication, which can be associated with reinterventions, infections, readmissions, and longer hospital stays. Occasionally, these bleedings may correspond to arterial hemorrhages, which require early identification and specific treatment. We reviewed two clinical cases of inadvertent arterial bleeding after Pacemaker implantation that required a high clinical suspicion together with a multidisciplinary evaluation of cardiologists, radiologists and interventional medicine that allowed a fast and effective endovascular approach.
Genetic alterations, RNA expression profiling and DNA methylation of HMGB1 in malignancies
Authors: Yu Shoukai , Qian Lingmei , Ma Jun
Published: June 2022

The high mobility group box 1 (HMGB1) is a potential biomarker and therapeutic target in various human diseases. However, a systematic, comprehensive pan‐cancer analysis of HMGB1 in human cancers remains to be reported. This study analysed the genetic alteration, RNA expression profiling and DNA methylation of HMGB1 in more than 30 types of tumours. It is worth noting that HMGB1 is overexpressed in malignant tissues, including lymphoid neoplasm diffuse large B‐cell lymphoma (DLBC), pancreatic adenocarcinoma (PAAD) and thymoma (THYM). Interestingly, there is a positive correlation between the high expression of HMGB1 and the high survival prognosis of THYM. Finally, this study comprehensively evaluates the genetic variation of HMGB1 in human malignant tumours. As a prospective biomarker of COVID‐19, the role that HMGB1 plays in THYM is highlighted.