bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trajectory Classification Method for Anchored Molecular Motor-Biopolymer Interactions in the C. elegans first Mitosis
Authors: Linehan John , Edwards Alan , Boudreau Vincent , Maddox Paul 
Published: September 2022

AbstractDuring zygotic mitosis, forces generated at the cell cortex are required for the separation and migration of paternally provided centrosomes, pronuclear migration, proper segregation of genetic material, and successful cell division. Identification of individual cortical force generating unitsin vivois necessary to study the regulation of microtubule dependent force generation throughout the cell cycle, to further understanding of asymmetric cell division, and to identify the molecular mechanism of force generation. Here we present a method to determine both the location and relative number of microtubule dependent cortical force generating units using single molecule imaging of fluorescently labelled dynein. Dynein behavior is modeled to differentiate and categorize trajectories that correspond to that which is cortically bound and interacting with a microtubule, and is cortically bound and not interacting with a microtubule. The categorization strategy recapitulates well known force asymmetries in the first mitosis of the C. elegans embryo. To evaluate the robustness of categorization, we RNAi depleted the microtubule subunit TBA-2 resulting in reduction of the number of trajectories categorized as engaged with a microtubule. This technique will be a valuable tool to provide new insight to the molecular mechanisms of dynein cortical force generation and its regulation as well as other instances wherein anchored motors interact with biopolymers (eg. Actin, tubulin, DNA).
TOPSIS analysis for sustainable redevelopment potential of abandoned infrastructure in Nigeria
Authors: Ogunnusi Mercy , Salman Huda , Laing Richard 
Published: September 2022

PurposeAbandonment poses a range of effects detrimental to the development of a country such as Nigeria. Restoring such infrastructure in a sustainable manner is a challenge identified in the literature. The aim of this study is to evaluate a novel approach – the technique for order preference by similarity to an ideal solution (TOPSIS) to identify the sustainability criteria for the redevelopment of abandoned infrastructure in Nigeria. The literature evidences use of TOPSIS in various development contexts, but not in the context of redevelopment of abandoned infrastructure.Design/methodology/approachThis study explores the potential of TOPSIS in the sustainable redevelopment of abandoned infrastructure in Nigeria through a combination of a quantitative method of data collection – questionnaire – and a case study. The case study focuses on the abandoned Federal Government Secretariat in Lagos. One hundred and sixty-one (161) participants responded to the questionnaire. Data collected were analyzed using TOPSIS analytical technique.FindingsRefurbishment is considered as the most sustainable alternative for the redevelopment of abandoned infrastructure. For criteria consideration, structural integrity and foundation categorized under the technological attributes ranked highest for refurbishment and conversion alternatives. Waste generation and prevention and profitability top the list for demolition and procurement respectively.Social implicationsThe social benefit of this study is to bring building considered to be an eyesore back into use.Originality/valueThe findings from the analysis orchestrates the importance of the built environment research concentrating on innovative frameworks for sustainable redevelopment of abandoned structures in the construction industry.
Walking the managerial tightrope: top management involvement in product innovation projects
Authors: Felekoglu Burcu , Durmusoglu Serdar S. , Maier Anja M. , Moultrie James 
Published: September 2022

PurposeThis study examines how technical drivers as well as social drivers influence organic communication and top management involvement (TMI) in new product development (NPD) projects. Technical drivers are of strategic importance and product innovativeness and social drivers are of intrinsic and extrinsic relevance. Organic communication is defined as continuous, bidirectional and informal communication between top management and the NPD teams. Further, arguing that TMI must be studied as a multifaceted construct, it is conceptualized to occur as guidance, active motivation and providing resources and creating a tolerant climate. Subsequently, the effect of TMI and organic communication on NPD performance is investigated.Design/methodology/approachThe data set, collected via surveys from top managers and project managers involved in 86 NPD projects in 85 firms, is analyzed using PLS structural equation modeling.FindingsThe authors show that the strategic importance of the project has a positive influence on TMI through active motivation, providing resources and creating a tolerant climate for innovation, but does not have an effect on guidance. Results also show that active motivation and organic communication improve budget and schedule adherence, whereas providing guidance and stimulating a tolerant climate have detrimental effects. In summary, the results show that only active motivation enhances all types of performance while stimulating a tolerant climate appears to have the opposite effect. The results revealed that organic communication between top management and the NPD team has a strong positive effect on all elements of TMI (providing guidance, actively motivating the NPD team, providing resources and creating a tolerant climate). In other words, when top management communicates with the NPD team throughout the project in an informal way and listens to them in addition to engaging in a one-way communication, they are more likely to be seen by the team as being deeply involved in the project.Practical implicationsExecutives must walk a managerial tightrope to actively motivate and to assist in providing resources, yet they must not be overbearing with direct guidance and must limit their tolerance for failures.Originality/valueInvolvement of key organizational actors such as top management and the link to project performance has attracted significant attention in research. However, nuanced empirical insights into the dyad of top management and project teams has so far been absent. The study’s findings detail the effect of technical and social drivers of top management involvement in new product development projects. Most notably, (1) the effect of motivation and stimulating a tolerant climate on performance, and (2) the effect of organic communication on top management involvement. Moreover, this study is unique in that it empirically examines TMI from both top management and team perspectives.
Tracing the density of human being: through a Levinasian anthropology of invisible otherness
Authors: Rapport Nigel 
Published: September 2022

AbstractFor Emmanuel Levinas, to study human nature is to ‘liberate human beings from the categories adapted uniquely for things’. This, paradoxically, is to occupy a standpoint where the human ‘no longer offers itself to our powers’: to go beyond the category‐thinking of cultural construction and to put what one consciously supposes – Self, Society, Culture, Nature – into question. The ‘liberation’ of human nature is an unconscious process that does not have the structure of intentionality but rather the character of inspiration. Examining the possible accommodation of a Levinasian philosophy within anthropology, this article pays particular attention to the human ‘density of being’ that, for Levinas, accompanies any individual life. It is impossible for Ego to know the Other, Levinas insists – subjectivity is ‘secret’, identity is ‘invisible’ – but otherness can nevertheless ‘inspire’ recognition and respect through its physical proximity. The article argues that a ‘cosmopolitan’ anthropology devoted to discerning the nature of a universal humanity might practise an artistry sufficient to identify the outline of that invisibility: the silhouette even if not the substance. Here are the traces of otherness that are evident, willy‐nilly, when the densities of being of individual human lives impact upon one another in social milieux.
Cochlear Neurotrophin‐3 overexpression at mid‐life prevents age‐related inner hair cell synaptopathy and slows age‐related hearing loss
Authors: Cassinotti Luis R. , Ji Lingchao , Borges Beatriz C. , Cass Nathan D. , Desai Aditi S. , Kohrman David C. , Liberman M. Charles , Corfas Gabriel 
Published: September 2022

AbstractAge‐related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. This progressive pathology often has psychological and medical comorbidities, including social isolation, depression, and cognitive decline. Despite ARHL's enormous societal and economic impact, no therapies to prevent or slow its progression exist. Loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs), a.k.a. IHC synaptopathy, is an early event in cochlear aging, preceding neuronal and hair cell loss. To determine if age‐related IHC synaptopathy can be prevented, and if this impacts the time‐course of ARHL, we tested the effects of cochlear overexpression of neurotrophin‐3 (Ntf3) starting at middle age. We chose Ntf3 because this neurotrophin regulates the formation of IHC‐SGN synapses in the neonatal period. We now show that triggering Ntf3 overexpression by IHC supporting cells starting in middle age rapidly increases the amplitude of sound‐evoked neural potentials compared with age‐matched controls, indicating that Ntf3 produces a positive effect on cochlear function when the pathology is minimal. Furthermore, near the end of their lifespan, Ntf3‐overexpressing mice have milder ARHL, with larger sound‐evoked potentials along the ascending auditory pathway and reduced IHC synaptopathy compared with age‐matched controls. Our results also provide evidence that an age‐related decrease in cochlear Ntf3 expression contributes to ARHL and that Ntf3 supplementation could serve as a therapeutic for this prevalent disorder. Furthermore, these findings suggest that factors that regulate synaptogenesis during development could prevent age‐related synaptopathy in the brain, a process involved in several central nervous system degenerative disorders.
The emergent role of mitochondrial surveillance in cellular health
Authors: Tjahjono Elissa , Kirienko Daniel R. , Kirienko Natalia V. 
Published: September 2022

AbstractMitochondrial dysfunction is one of the primary causatives for many pathologies, including neurodegenerative diseases, cancer, metabolic disorders, and aging. Decline in mitochondrial functions leads to the loss of proteostasis, accumulation of ROS, and mitochondrial DNA damage, which further exacerbates mitochondrial deterioration in a vicious cycle. Surveillance mechanisms, in which mitochondrial functions are closely monitored for any sign of perturbations, exist to anticipate possible havoc within these multifunctional organelles with primitive origin. Various indicators of unhealthy mitochondria, including halted protein import, dissipated membrane potential, and increased loads of oxidative damage, are on the top of the lists for close monitoring. Recent research also indicates a possibility of reductive stress being monitored as part of a mitochondrial surveillance program. Upon detection of mitochondrial stress, multiple mitochondrial stress‐responsive pathways are activated to promote the transcription of numerous nuclear genes to ameliorate mitochondrial damage and restore compromised cellular functions. Co‐expression occurs through functionalization of transcription factors, allowing their binding to promoter elements to initiate transcription of target genes. This review provides a comprehensive summary of the intricacy of mitochondrial surveillance programs and highlights their roles in our cellular life. Ultimately, a better understanding of these surveillance mechanisms is expected to improve healthspan.
Evidence of cancer progression as the cause of death in men with prostate cancer in Sweden
Authors: Orrason Andri Wilberg , Styrke Johan , Garmo Hans , Stattin Pär 
Published: September 2022

ObjectiveTo assess the strength of the evidence indicative of prostate cancer (PCa) progression as the adjudicated cause of death, according to age at death and PCa risk category.Patients and MethodsUsing data from the Prostate Cancer data Base Sweden, we identified a study frame of 5543 men with PCa registered as the cause of death according to the Cause of Death Register. We assessed the evidence of PCa progression through a review of healthcare records for a stratified sample of 495/5543. We extracted data on prostate‐specific antigen levels, presence of metastases on imaging, and PCa treatments, and quantified the evidence of disease progression using a points system.ResultsBoth no evidence and moderate evidence for PCa progression was more common in men aged >85 years at death than those aged <85 years (29% vs 14%). Among the latter, the proportion with no evidence or moderate evidence for PCa progression was 21% for low‐risk, 14% for intermediate‐risk, 8% for high‐risk, and 0% for metastatic PCa. In contrast, in men aged >85 years, there was little difference in the proportion with no evidence or moderate evidence of PCa progression between PCa risk categories; 31% for low‐risk, 29% for intermediate‐risk, 29% for high‐risk, and 21% for metastatic PCa. Of the 5543 men who died from PCa, 13% (95% confidence interval 5–19%) were estimated to have either no evidence or moderate evidence of PCa progression.ConclusionsWeak evidence for PCa progression as cause of death was more common in older men with PCa and in those with low‐risk PCa. This has implications for interpretation of mortality statistics especially when assessing screening and early treatment of PCa because the beneficial effect of earlier diagnosis could be masked by erroneous adjudication of PCa as cause of death in older men, particular those with localised disease at diagnosis.
Concentration‐dependent effects of proinflammatory cytokines on barrier function and tight junction protein expression in brain microvascular endothelial cells and the hypothermic and hyperthermic effects on tight junction protein expression
Authors: Matsui Tomohiro , Mochiduki Yuji , Yoshida Yusuke , Nitta Takenori 
Published: September 2022

AbstractObjectiveThe mechanisms underlying therapeutic hypothermia, which protects neurons following severe brain damage, are only partially understood. We previously demonstrated that hypothermia reduced, whereas hyperthermia augmented, the release of tumor necrosis factor (TNF)‐α and interleukin (IL)‐17. Cerebral ischemia causes the loss of the blood–brain barrier (BBB) integrity, thereby increasing cerebral vascular permeability, which directly contributes to vasogenic edema, hemorrhagic transformation, and increased mortality. Brain microvascular endothelial cells (BMVECs) are a major component of BBB and tight junction proteins (TJPs) in these cells maintain the BBB integrity. In this study we determined the mechanisms underlying this treatment by measuring the effects of TNF‐α and IL‐17 on BMVEC barrier function and TJP expression in BMVECs, and by evaluating the effects of hypothermia and hyperthermia on TJP expression.MethodsThe barrier function of BMVECs was evaluated by measuring transepithelial electrical resistance (TEER). The expression of several TJPs, such as claudin‐5 and junctional adhesion molecule (JAM)‐B, was measured at the mRNA and protein levels using real‐time polymerase chain reaction and immunocytochemistry, respectively.ResultsTNF‐α and IL‐17 decreased TEER values, and TNF‐α decreased claudin‐5 and JAM‐B mRNA and protein levels, whereas IL‐17 decreased JAM‐B mRNA and protein levels, and all of these effects were concentration‐dependent. Compared with normothermia, claudin‐5 and JAM‐B proteins were not affected by hypothermia, whereas JAM‐B protein was reduced by hyperthermia.ConclusionThe hypothermic suppression of TNF‐α and IL‐17 release may contribute to the maintenance of BBB function by ameliorating the decrease of TJP(s). In contrast, hyperthermia may decrease barrier function through a decrease in JAM‐B expression. However, the contribution of changes in the JAM‐B expression to the barrier function of BMVECs remains to be clarified.
Contact sensitizations in massage therapists with occupational contact dermatitis: Patch test data of the Information Network of Departments of Dermatology, 2008–2020
Authors: Brans Richard , Schröder‐Kraft Claudia , Bauer Andrea , Weisshaar Elke , Skudlik Christoph , Geier Johannes ,   for the IVDK
Published: September 2022

AbstractBackgroundMassage therapists are particularly exposed to constituents of massage preparations, wet work and mechanical strain and therefore, at high risk to develop occupational dermatitis (OD).ObjectivesTo describe the sensitization spectrum of massage therapists with OD.Patients and MethodsIn a retrospective study, patch test data of patients with OD (128 massage therapists and 24 374 patients working in other professions) collected by the Network of Departments of Dermatology (IVDK, 2008–2020) were analysed.ResultsHand dermatitis (91.4%) and allergic contact dermatitis (34.4%) were common in massage therapists with OD. Most frequent were sensitizations to fragrances/essential oils which were found in 54 (42.2%) massage therapists and thus, more often than in other patients with OD. Concomitant positivity to several fragrances/essential oils was frequent. In 8 (14.8%) of the 54 massage therapists, sensitizations to fragrances/essential oils were not detected with the baseline series, but only with special fragrance series.ConclusionsAllergic contact dermatitis is common in massage therapists with OD and is mainly caused by fragrances and essential oils. Hence, massage therapists should be aware of this risk. When OD is suspected, not only the baseline series, but also special fragrance series should be patch tested in this occupational group.
Management of high and low risk malignant polyps: a population‐wide analysis
Authors: Zammit Andrew P. , Panahi Seyed E. , Brown Ian , Hooper John D. , Clark David A. , Riddell Andrew D. 
Published: September 2022

AbstractAimThe management of malignant polyps is a treatment dilemma in selecting between polypectomy and colorectal resection. To assist clinicians, guidelines have been developed by the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to provide treatment recommendations.MethodsThis study compared management strategy based on the ACPGBI risk categorization for malignant polyps. Univariable and multivariable statistical analysis was undertaken to assess the factors predicting management strategy. A population‐wide analysis was performed of 1646 malignant polyps and the factors that predicted their management strategy, from Queensland, Australia, from 2011 to 2019.ResultsOverall, 31.55% of patients with very low or low risk disease proceeded to resection. Of those with high or very high risk disease, 36.69% did not proceed to resection. In very low and low risk polyps, age (P = 0.003) and polyp location (P < 0.001) were significantly different between the colorectal resection group and the polypectomy alone group. In those with very high or high risk polyps age (P < 0.001), type of facility (public or private) for the colonoscopy (P = 0.037), right colonic polyps compared to left colonic polyps (P = 0.015) and rectal polyps (P < 0.001) and mismatch repair mutations present (P = 0.027) were predictive of resection in high risk disease using a multivariable model.ConclusionOver 30% of patients with very low and low risk malignant polyps proceeded to resection, against the advice of guidelines. Furthermore, over 35% of patients with very high or high risk malignant polyps did not proceed to resection. Education strategies may improve management decision choices. Furthermore, improvements in data collation will improve the understanding of management choices in the future.
Savor the flavor: A randomized double‐blind study assessing taste‐enhanced placebo analgesia in healthy volunteers
Authors: Zunhammer Matthias , Goltz Gerrit , Schweifel Maximilian , Stuck Boris A. , Bingel Ulrike 
Published: September 2022

AbstractPlacebo effects substantially contribute to analgesic treatment outcomes and might be leveraged to enhance gold‐standard treatments. The taste of oral medications has been proposed to boost placebo effects. Here, we aimed at estimating how far the taste of an oral medication enhances placebo analgesia. We conducted a randomized, double‐blind, between‐group, single‐visit study, with pre‐treatment baseline. Over the course of three substudies, 318 healthy volunteers (297 included) were tested in a clinical trial setting. Participants were subjected to experimental tonic cold water pain (cold pressor test) before and after receiving taste‐neutral (water), or bitter (quinine), or sweet (saccharin), or no placebo drops. Pre‐ versus post‐treatment changes in area under the pain rating curve, the main outcome, indicated that placebo treatment showed a small analgesic effect versus no treatment. Added taste induced placebo enhancement in the very small effect size range, but accounted for a substantial portion of the overall placebo effect. No noteworthy advantage of sweet over bitter placebo was observed. An exploration of heart rate (HR) recordings indicated that placebo treatments were associated with an increase in peak HR‐response to cold water, but these were not associated with placebo analgesia at an individual level. Placebo treatments were associated with minimal side effects. These results indicate that added taste may be an easy‐to‐implement, cost‐effective, and safe way to optimize treatment outcomes and that taste‐neutral preparations may reduce placebo‐related outcome variance in clinical trials. Further studies are needed to test if these findings can be translated into clinical scenarios.
Lipidomics of cyclophosphamide 4‐hydroxylation in patients receiving post‐transplant cyclophosphamide
Authors: Navarro Sandi L. , Zheng Zihan , Randolph Timothy W. , Nakamura Ryotaro , Sandmaier Brenda M. , Hockenbery David , McCune Jeannine S. 
Published: September 2022

AbstractBiomarker‐guided dosing may improve the efficacy and toxicity of cyclophosphamide (CY); however, clinical studies evaluating their association with the area under the plasma concentration–time curve (AUC) of CY and its metabolites are time‐ and resource‐intensive. Therefore, we sought to identify lipidomic biomarkers associated with the time‐varying differences in CY formation clearance to 4‐hydroxycyclophosphamide (4HCY), the principal precursor to CY's cytotoxic metabolite. Hematopoietic cell transplant (HCT) patients receiving post‐transplant CY (PT‐CY) were enrolled, cohort 1 (n = 25) and cohort 2 (n = 26) donating longitudinal blood samples before they started HCT (pre‐HCT), before infusion of the donor allograft (pre‐graft), before the first dose of PT‐CY (pre‐CY) and 24 h after the first dose of PT‐CY (24‐h post‐CY) which is also immediately before the second dose of CY. A total of 409 and 387 lipids were quantitated in the two cohorts, respectively. Associations between lipids, individually and at a class level, and the ratio of 4HCY/CY AUC (i.e., 4HCY formation clearance) were evaluated using linear regression with a false discovery rate <0.05. There were no individual lipids that passed control for false discovery at any time point. These results demonstrate the feasibility of lipidomics, but future studies in larger samples with multiple omic tools are warranted to optimize CY dosing in HCT.