bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gravity beyond Einstein? Yes, but in which direction?
Authors: Kazanas Demosthenes , Papadopoulos Demetrios , Christodoulou Dimitris 
Published: July 2022

We present qualitative arguments in favour of an extension of the theory of the gravitational interaction beyond that resulting from the Hilbert–Einstein action. To this end, we consider a locally conformal invariant theory of gravity, discussed some 30 years ago by Mannheim and Kazanas. We discuss its exact solution of the static, spherically symmetric configurations and, based on these, we revisit some of the outstanding problems associated with gravity, high energy interactions and sketch potential resolutions within the conformal gravity framework.
This article is part of the theme issue ‘The future of mathematical cosmology, Volume 2’.
Impact of SARS-Cov-2 on Clinical Trial Unit workforce in the United Kingdom; An observational study
Authors: Delanerolle Gayathri , Hu Jintong , Cavalini Heitor , Yardley Lucy , Barnard-Kelly Katharine , Elliot Katheryn , Raymont Vanessa , Rathod Shanaya , Shi Jian Qing , Phiri Peter 
Published: July 2022

AbstractObjectiveThe clinical trial unit (CTU) workforce in the UK have been delivering COVID-19 research since the inception of the pandemic. Challenges associated with COVID-19 research have impacted the global healthcare communities differently. Thus, the overall objective of the study was to determine the mental health impact among CTU staff working during the COVID-19 pandemic.DesignA mixed-methods based observational study was designed using a new workforce impact questionnaire using validated mental health assessments of Vancouver Index of Acculturation (VIA), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Pandemic Stress Index (PSI), Burnout Assessment Too-12 (BAT-12), General Self Efficacy Scale (GSE) and The Everyday Discrimination Scale (EDS).SettingThe Qualtrics platform was used to deploy the questionnaire where a quantitative analysis was conducted. The qualitative part of the study used the Microsoft Teams digital application to complete the interviews.ParticipantsAll participants were CTU staff within the United Kingdom.
Mechanistic model for booster doses effectiveness in healthy, cancer and immunosuppressed patients infected with SARS-CoV-2
Authors: Voutouri Chrysovalantis , Hardin C. Corey , Naranbhai Vivek , Nikmaneshi Mohammad R. , Khandekar Melin J. , Gainor Justin F , Stylianopoulos Triantafyllos , Munn Lance L. , Jain Rakesh K. 
Published: July 2022

AbstractSARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, vaccines are based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity, validate it with available clinical data, and predict vaccine effectiveness for varied vaccine platforms in the setting of variants with ability to escape immunity, increased virulence, or enhanced transmissibility. We further account for concurrent cancer or underlying immunosuppression. The model confirms enhanced immunogenicity following booster vaccination in immunosuppressed patients but predicts at least one more booster dose is required for these individuals to maintain protection. We further studied the impact of variants on immunosuppressed individuals as a function of the interval between multiple booster doses. Our model is useful for planning future vaccinations, and tailoring strategies to risk groups.Significance StatementCurrent SARS-CoV-2 vaccines are effective at preventing COVID-19 or limiting disease severity in healthy individuals, but effectiveness is lower among patients with cancer or immunosuppression. Here, we address the need for predictions of vaccine effectiveness over time by building on our mathematical framework to account for vaccination-induced immunity. A booster dose of both mRNA vaccines can induce a robust enhancement of both antibody levels and numbers of pertinent types of adaptive immune cells, which is predicted to provide sufficient protection for more than one year in healthy patients. However, our model suggests that for immunosuppressed people or patients with cancer receiving an immunosuppressive treatment, the booster effect may wane, and perhaps could be considered on a more frequent basis.
A signal-seeking Phase II trial of Durvalumab and Tremelimumab Focused on Advanced, Rare and Less Common Cancers
Authors: Thavaneswaran Subotheni , Lin Frank P , Kansara Maya , Grady John P , Espinoza David , Joshua Anthony M , Grimison Peter , Craft Paul , Cosman Rasha , Lee Chee , Harwood Kathleen , Chinchen Sarah , Corpuz Theresa , Ballinger Mandy , Sebastian Lucille , Simes John , Thomas David 
Published: July 2022

ABSTRACTImmune checkpoint blockade impedes the negative regulatory signals for T-cell response and permits more effective immune detection and eradication of cancer cells. This single-arm phase II clinical trial (ACTRN12616001019493) within the Molecular Screening and Therapeutics (MoST) program evaluates the clinical activity and safety of combination immunotherapy with durvalumab and tremelimumab in patients with advanced cancers, prioritsing rare cancers (<6 per 100,000 annual incidence) and patients having failed standard treatments for their cancer type.MethodsEligible patients were determined by the molecular tumour board based on the absence of actionable genomic findings (n=64) and biomarker enriched (n=48) at screening. Patients received durvalumab 1500 mg and tremelimumab 75 mg every four weeks for 4 cycles, followed by durvalumab alone for another 9 cycles. The primary endpoint was progression-free survival at 6 months (PFS6) and secondary endpoints included objective response, time to progression (TTP) on trial to TTP on prior therapy (TTP2/TTP1>1.3), overall survival and treatment tolerability.ResultsBetween December 2016 and 2019, 112 patients were enrolled on the study. There was a female predominance (55%), most had an ECOG performance status of 0 (66%), aged <65 years (75%), with rare cancers (84%). The PFS6 rate was 32% (95% CI 23 to 40%); 16 of 112(14%) achieved an objective response; TTP2/TTP1>1.3 for 22 of 63 (35%) patients with an evaluable ratio; median overall survival 11.9 months (95% CI 11.0 to 14.8), and there were no new safety concerns. High tumour cell PD-L1 correlated with improved PFS and OS and TMB with PFS alone. More PD-1+CD4+ T-cells and circulating follicular T-helper (cTfh) cells at baseline were strongly associated with better PFS and OS.ConclusionDurvalumab plus tremelimumab demonstrated a signal of clinical activity in treatment-refractory patients with rare cancers. A PFS6 of 32% and 35% of patients achieving a TTP2/TTP1>1.3 suggests an improved disease trajectory on trial. Translational correlates provided insights into biological associations with clinical outcomes across tumour types.
Booked Appointments System: An evaluation of the acceptability and feasibility of booked appointments in a large HIV clinic in Johannesburg, South Africa
Authors: Long Lawrence , Batiancila Rachel , Girdwood Sarah , Majuba Pappie , Lince-Deroche Naomi 
Published: July 2022

AbstractBackgroundLong queues and overcrowding are common in many of South Africa’s public healthcare facilities and may negatively impact on the quality of care provided. In HIV-related services, this problem may also affect retention. Healthcare facilities that rely on a system of patient appointments scheduled by day, and not by time, may exacerbate these issues. This study aims to improve retention and care by understanding the challenges and advantages related to the current system of booking appointments and assessing the potential for alternative systems.MethodsThe study was conducted in Johannesburg, South Africa at an outpatient HIV treatment clinic set within a large, urban secondary-level teaching hospital. The study is cross-sectional and includes structured interviews with providers and patients. Medical records are linked with patient interviews and observations to determine actual waiting times.Results245 patients and 6 providers were interviewed. Of the patients interviewed, 64% were female, and 96% were Black African. Nearly a fifth of patients (19%) lost an average of USD 32 in income when attending their appointment. The most common reason for missing an appointment was that they could not be absent from work (40%), but despite this most respondents (65%) do not believe they face any challenges with the current system of booking appointments. Being able to arrive at a time convenient for them was considered a benefit by many (49%), but some (29%) recognized that this may result in overcrowding. The majority of respondents were in favor of appointments offered as a block of time in the morning or afternoon (88%) as well as appointments after work hours (85%). In comparison only just over half (58%) were in favor of booking appointments at a specific time. Most respondents (79%) believe the largest benefit to morning/afternoon block appointments would be the ability to show up at their own convenience during the block of time.ConclusionsPatients value convenience highly. This may be explained by the need to be flexible around work schedules and transport options. It might be worth exploring a booking system in which patients are given a morning or afternoon appointment rather than a day. This may improve the distribution of patients throughout the day and as a result retention and care in a high-prevalence HIV setting.
3D-Printing in Radiation Oncology: Development and Validation of Custom 3D-Printed Brachytherapy Alignment Device and Phantom
Authors: Provenzano Destie , Aghdam Hamid , Goyal Sharad , Loew Murray , Rao Yuan James 
Published: July 2022

AbstractBrachytherapy seeks to treat cancer through insertion of radioactive sources aligned by needles within standardized blocking templates. However, many patients have anatomy that does not conform to standard tools. We created a 3D printed device to provide customized needle alignment for a patient. Device was validated through CT scan and treatment plan creation on a custom anatomical phantom based on patient data. CT scan of a cervix tumor from anonymized patient data was used to develop a 3D printed brachytherapy alignment tool and phantom anatomical mold. Multiple materials were evaluated to match patient anatomy in density and Hounsfield Units present on CT scan, with additional considerations for toxicity, compliance, and practicality. Alignment device and molds were developed in PLA. Silicone of T20 hardness was used to create relevant anatomical organs (Uterus, Rectum, Bladder). Tumor tissue was mimicked by addition of 1CC of Iodine contrast agent to silicone. Device and needles were arranged, inserted into anatomical phantom, and scanned by CT to mimic brachytherapy procedure. 3D printed Silicone uterus of 1.08 g/cm^3 and 40 HU mimicked human uterus on CT scan. Constructed uterus dimensions of 6.5 cm x 5.5 cm x 3.3 cm were verified on imaging to be within + 1 mm of original patient scan. The 1 CC of contrast agent provided sufficient differentiation of “tumor” ring from “tissue.” CT scan and treatment plan creation verified that the alignment device provided correction insertion of needles into the phantom tumor tissue and uterus. This pilot study provides a potential methodology to develop future anatomical phantoms and alignment devices from CT scans of patient data. Additional modifications could make this a viable training tool for future residents and medical students to learn brachytherapy.Key Points3D printing can be leveraged to create a Brachytherapy alignment device from patient’s anatomy.Anatomical phantom can be generated from 3D printing for use testing device or for training.Relevant materials to create phantom that mimic patient’s anatomy on CT scan.Generation of a treatment plan based on CT scan was able to validate device and phantom
Characterization of an ant colony (Paraponera clavata) during rest and relocation phases: an experimentally induced protocol
Authors: Rodriguez Alexandra , Fresneau Dominique , Cabanesa Guénaël 
Published: July 2022

AbstractUnderstanding societies of individuals is a challenging task. In several ant species individuals seem to have the same physical characteristics and, in principle, could assume any role the social environment requires. However, most ants’ societies present a caste organization in their colonies with particular roles. For the biologist understanding the complex dynamics ruling a colony is hard due to the difficulty of collecting and classifying long term ant activities in the field. The relocation phenomena which generally correspond to perturbation phases suffered by ant colonies are critical moments in the colony history and require rapid and effective response from workers in order to ensure the survival of the colony and its setup in a new safe nest. How the colonial group deals with this process? Is there a particular organization of the workers during the relocation periods? Here, we applied an experimentally induced protocol in the laboratory combined with behavioral observations and hierarchical classifications in order to identify social roles in a ponerine species,Paraponera clavata, and the repartition of labor during two resting periods and two relocation phases. The method provided significant information concerning the social dynamics of ant colonies and contribute to understand how species copes with a novel and stressing situation conducing to the occupation of a novel available nest.
Transcriptome network analysis link perinatalStaphylococcus epidermidisinfection to microglia reprogramming in the immature hippocampus
Authors: Gravina Giacomo , Ardalan Maryam , Chumak Tetyana , Rydbeck Halfdan , Wang Xiaoyang , Ek Carl Joakim , Mallard Carina 
Published: July 2022

AbstractStaphylococcus epidermidis(S. epidermidis) is the most common nosocomial pathogen in preterm infants and associated with increased risk of cognitive delay, however, underlying mechanisms are unknown. We employed morphological, transcriptomic and physiological methods to extensively characterize microglia in the immature hippocampus followingS. epidermidisinfection. 3D morphological analysis revealed activation of microglia afterS. epidermidis. Differential expression combined with network analysis identified NOD-receptor signalling and trans-endothelial leukocyte trafficking as major mechanisms in microglia. In support, active caspase-1 was increased in the hippocampus and using the LysM-eGFP knock-in transgenic mouse, we demonstrate infiltration of leukocytes to the brain together with disruption of the blood-brain barrier. Our findings identify activation of microglia inflammasome as a major mechanism underlying neuroinflammation following infection. The results demonstrate that neonatalS. epidermidisinfection share analogies with S. aureus and neurological diseases, suggesting a previously unrecognized important role in neurodevelopmental disorders in preterm born children.
Analytical editorial: Ensuring the future of our world: innovation, management and governance for sustainable growth
Authors: Alonso Dos Santos Manuel , Huertas González-Serrano María , Staniewski Marcin Waldemar 
Published: July 2022

PurposeThis article presents the Special Issue (SI, 35-2) of ARLA, edited (not exclusively) with the best articles from the specialized conference of the Academy of Innovation, Entrepreneurship and Knowledge (ACIEK, 2021) conference and performs a bibliometric analysis on innovation, management, governance and sustainable growth.Design/methodology/approachGuest editors conduct a quantitative and qualitative analysis of the scholarly literature by examining the characteristics of publications and how articles published in this SI contribute to their growth.FindingsInnovation, management and governance for sustainable growth is an area that revolves around five points: (1) sustainable innovation in SMEs, (2) technological innovation, social capital and information patents to create value chains and financial development in the textile industry, (3) knowledge management and competitiveness for growth and productivity, (4) social entrepreneurship, business ecosystems and startups for sustainable development and (5) marketing-based business strategies for sustainable development.Practical implicationsFrom the analysis conducted, it is concluded that more research is needed on knowledge management and competitiveness in developing countries, such as Latin American and African countries, and to compare the results with more developed countries.
Lean manufacturing and firms’ financial performance: the role of strategic supplier partnership and information sharing
Authors: Islami Xhavit 
Published: July 2022

PurposeThe purpose of this paper is to examine the mediating role of strategic supplier partnership and moderating role of information sharing (IS), in the relationship between lean manufacturing and firms’ financial performance (FP).Design/methodology/approachUtilizing the contingency approach, this study develops a research model to validate the proposition that a proper integration of supply chain (SC) practices enhances the financial performance of the firm. The study uses data from one hundred and fifty-seven manufacturing firms. The results are generated on structural equation modeling (SEM) using AMOS software.FindingsThe study finds that strategic supplier partnership partially mediates the relationship between lean manufacturing and FP, whereas, empirically, it could not demonstrate that IS significantly moderates the relationship between lean manufacturing and FP.Practical implicationsThe paper theoretically develops logic for and empirically shows that strategic supplier partnership is an appropriate practice for mediating the impact of lean manufacturing on FP.Originality/valueThis strategic supply chain integration contributes to theory and demonstrates that SC practices’ correct synchronization and orchestration may realize superior FP. In addition, this research provides a sustainable strategic SC model that creates value and provides a competitive advantage for firms in the long term.
Experimental study on performance of CFRP-strengthened RC beams with geopolymer and epoxy
Authors: Liu Baocheng , Liu Jinliang , Wen Yanqian , Hu Qinglin , Liu Liang , Zhao Shili 
Published: July 2022

PurposeIn this paper, to obtain shear and bending performance of carbon fiber-reinforced polymer (CFRP)-strengthened beams bonded by geopolymers, the effects of impregnated adhesive types, strengthened scheme, CFRP layer and pre-cracked width are investigated, and the performance of CFRP-strengthened beams is validated by the establishment of Finite Element Models (FEMs).Design/methodology/approachIn this paper, static loading test and finite element analysis of epoxy-CFRP-strengthened (ECS) and geopolymer-CFRP-strengthened (GCS) were carried out, and the bearing capacity and stiffness were compared, the results show that GCS reinforced concrete (RC) beam is feasible and effective.FindingsThe bearing capacity, crack distribution and development, load–deflection curves of GCS RC beams with different pre-crack widths were investigated. The reinforcement effect of geopolymer achieves the same as epoxy, effectively improving the ultimate bearing capacity of the beam, with a maximum increase rate of 28.9%. The failure mode of CFRP is broken in the yield failure stage of GCS RC beam with reasonable strengthening form, and the utilization rate of CFRP is improved. CFRP-strengthened layers, pre-cracked widths significantly affect the mechanical properties, and deformation properties of the strengthened beams.Originality/valueCompared with ECS RC beams, the bearing capacity and stiffness of GCS RC beams are similar to or even better, indicating that GCS RC beam is feasible and effective. It is a new method for CFRP-strengthened beams, which not only conforms to the concept of national ecological civilization construction, but also provides an economical, environmentally friendly and excellent performance solution for structural reinforcement.
Overwhelmed by family, but supported by likeminded, trustworthy coworkers: effects on role ambiguity and championing behaviors
Authors: De Clercq Dirk , Pereira Renato 
Published: July 2022

PurposeThis study addresses how and when the experience of family-induced work strain might steer employees away from efforts to promote innovative ideas. In particular, it proposes a mediating role of role ambiguity and moderating roles of two coworker resources (goal congruence and goodwill trust) in this process.Design/methodology/approachThe research hypotheses are tested with data obtained from a survey administered among employees who work in a professional services organization.FindingsAn important explanatory mechanism that links family interference with work to diminished championing efforts is that employees hold beliefs that their job roles are unclear. The extent to which employees share work-related mindsets with coworkers, as well as their belief that coworkers are trustworthy, attenuate this harmful effect.Practical implicationsFor HR managers, the study shows a clear danger that threatens employees who feel drained by significant family demands: The negative situation may escalate into work-related complacency (diminished championing), which then may generate even more hardships. As it also reveals though, employees can leverage high-quality coworker relationships to contain this danger.Originality/valueThis study adds to HR management research by investigating the role of negative spillovers from family to work in predicting idea championing, as explained by negative beliefs about job-related information deficiencies but buffered by high-quality coworker relationships.
Knockout of cardiac troponin I‐interacting kinase leads to cardiac dysfunction and remodelling
Authors: Qu Huilin , Zhang Yue , Zhang Wei , Zhu Yaxin , Xu Ruixia 
Published: July 2022

AbstractCardiac troponin I‐interacting kinase (TNNI3K) is a cardiac‐specific kinase that has been identified as a diagnostic marker and a therapeutic target in cardiovascular diseases. However, the biological function of TNNI3K in cardiac dysfunction and remodelling remains elusive. In the present study, a Tnni3k cardiomyocyte‐specific knockout (Tnni3k‐cKO) mouse model was established. Echocardiography was used to evaluate cardiac function in mice. Heart failure markers were detected using enzyme‐linked immunosorbent assay. Haematoxylin and eosin staining, wheat germ agglutinin staining, Masson's trichrome staining, Sirius red staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining were used to assess histopathological changes, cardiac hypertrophy, collagen deposition and myocardial apoptosis, respectively. Expression levels of TNNI3K, apoptosis‐related proteins, and p38 mitogen‐activated protein kinase were measured using Western blot analysis. Compared to wild‐type controls, cardiac dysfunction and cardiac remodelling of Tnni3k‐cKO mice increased gradually with age. Tnni3k‐cKO mice exhibited cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. Upregulation of cleaved caspase‐3 in Tnni3k‐cKO mice appeared to be related to phosphorylation and activation of the p38 mitogen‐activated protein kinase signalling pathway. In conclusion, this study shows that TNNI3K is essential for cardiac development and function, providing new insights into the development of novel therapeutic strategies for cardiac diseases.