bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical delivery of PD‐1 inhibitors with laser‐assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns
Authors: Christensen Rikke L. , Hendel Kristoffer K. , Persson Daniel P. , Husted Søren , Olesen Uffe H. , Haedersdal Merete 
Published: December 2021

AbstractBackground and ObjectivesCurrent cancer immunotherapeutic treatment with PD‐1 inhibitors is administered systemically. However, a local treatment strategy may be advantageous as it could provide targeted drug delivery as well as attenuate side effects seen with systemic treatments. For keratinocyte cancers, where surgical excision is not always applicable, an alternate local treatment approach would be beneficial. This study aims to examine cutaneous pharmacokinetics and biodistribution of the PD‐1 inhibitor nivolumab, locally delivered either by ablative fractional laser (AFL)‐assisted passive diffusion or active intradermal injection, in vivo.Materials and MethodsIn vivo pig skin was either exposed to CO2 AFL (80 mJ/mb by two stacked pulses of 40 mJ/mb) at 5% or 15% density followed by topical application of nivolumab (1 mg/ml, 100 µl/10 × 10 mm) or intradermally injected with nivolumab (1 mg/ml, 100 µl). Cutaneous nivolumab delivery was evaluated at different timepoints (0, 1, 2, 4 hours and 2 days) at two tissue depths (100–800 and 900–1600 µm) by ELISA. Visualization of cutaneous biodistribution was shown in vertical tissue sections using HiLyte FluorTM 488 SE labeled nivolumab for fluorescence microscopy whereas nivolumab was DOTA‐tagged with Dysprosium before the laser ablation‐inductively coupled plasma‐mass spectrometry analysis (LA‐ICP‐MS).ResultsOur in vivo study revealed different pharmacokinetic and biodistribution patterns for the AFL‐ and injection techniques. A superficial horizontal band‐like uptake of nivolumab was provided with AFL‐assisted passive diffusion whereas a deep focal deposition was seen with active intradermal injection, compared with controls showing remnant deposition on the skin surface. AFL‐assisted nivolumab uptake in upper dermis peaked after 4 hours (p < 0.01). The cutaneous concentration of nivolumab achieved by intradermal injection was markedly higher than with AFL, the highest deposition with intradermal injection was detected at time 0 hours in both upper and deep dermis (p < 0.01) and decreased throughout the study period, although the concentration remained higher compared with saline control injections at all time points (0 hours –2 d) (p < 0.01).ConclusionLocal cutaneous delivery of nivolumab with either AFL or intradermal injection revealed two different pharmacokinetic and biodistribution patterns. Passive AFL‐assisted diffusion of nivolumab resulted in enhanced uptake after 4 hours, while intradermal actively injected nivolumab showed immediate enhanced cutaneous deposition with retention up to 2 days after injection. The two local delivery techniques show potential for development of individualized treatment strategies depending on the clinical tumor appearance.
THE PSYCHOLOGY OF LEADERSHIP
Authors: Karr Ron 
Published: December 2021

AbstractThe author discusses what he calls the “Velocity Mindset®… Borrowing from the physics definition of speed with direction, it means that expending effort of any kind must be coupled with a clear view of the desired outcome or results.” He explains the importance of stories to our life and work; those we tell ourselves and those we hear from others. Unfortunately, they can be self‐limiting and just plain untrue. He further contends that “all the stories we tell ourselves—about ourselves or others, both positive and negative—are fueled by emotion. If the story and the emotion behind it are positive, then they serve you well and keep you moving forward. But if they are negative, then you need to change the story.” He writes about hormones in our body that “have effects on our moods and behaviors.” The three hormones he writes about are Cortisol, Oxytocin, and Dopamine. Cortisol sometimes corresponds to stress. Oxytocin is “produced in response to outside stimuli such as words or gestures interpreted as friendliness, interest, or support.” Dopamine is a “built‐in reward system for activities or actions that satisfy our needs.” The encouraging news is that “we are psychologically capable of benefiting ourselves and those around us.”
Fabrication of Sophisticated Microstructures using Weak Support in 3D Printing
Authors: Yu Zhongwei , Deng Xinghong , Shao Guangbin , Li Longqiu 
Published: December 2021

AbstractProjection‐based stereolithography (PSL) is one of the most competitive 3D printing technologies in fabricating complex microstructures because of its high accuracy and remarkable efficiency. Due to the layer‐by‐layer forming manner, some structures with cantilever features tend to collapse in the PSL process, for which support structures are required. However, the design, adding, and post‐treatment of traditional support structures can be extremely time‐consuming, and the manual removal step is always destructive and sometimes impossible, thus not suitable for sophisticated microstructures. Here a simple 3D printing method is proposed to fabricate sophisticated microstructures rapidly and precisely using weak support. Grayscale projection is used to produce partially cured photopolymer as weak support, which fills the lower space of overhanging structures and is constrained by a fully cured wall structure. The weak support is sufficient to support the printed parts while easy to remove because of incomplete photocured state. To determine the curing state of weak support, curing characteristics of the resin are measured and the relationship between curing energy and support effectiveness is investigated. Improvement in efficiency and applicability is observed in fabricating sophisticated microstructures using weak support method, which gives a promising solution to fabricate fragile microstructures with inaccessible overhang characteristics.
Radiographic validation of a self‐report instrument for hallux valgus
Authors: Gupta Vatsal , Lingham Aranghan , Marshall Michelle , Rathod‐Mistry Trishna , Menz Hylton B. , Roddy Edward 
Published: December 2021

AbstractBackgroundHallux valgus (HV) is a common condition causing substantial morbidity. Radiographic assessment is the gold standard for grading severity but is not always feasible in clinical/research settings. HV line‐drawings, consisting of five drawings for each foot depicting a sequential increase in HV angle of 15°, have been clinically validated for self‐reporting severity. We aimed to undertake radiographic validation of this self‐report instrument.MethodsAdults aged ≥50 from four GP practices were sent a health survey. Responders self‐reported HV severity for each foot using the line‐drawing instrument. Those reporting foot pain in the last year had radiographs taken at a research clinic from which intermetatarsal, hallux abductus and hallux interphalangeal abductus angles were calculated. Ten feet were randomly selected for each HV line‐drawing grade for both feet. Associations between self‐reported HV line drawings and radiographic measurements were assessed using Spearman's ρ correlation coefficients, mean radiographic angle measurement (95% confidence interval) and one‐way analysis of variance.ResultsIncreasing HV line‐drawing grade was positively correlated with radiographic measurements for intermetatarsal and hallux abductus angles (Spearman's ρ = 0.602, p < 0.001; 0.821, p < 0.001, respectively). Hallux interphalangeal abductus angle showed an inverse correlation with increasing line‐drawing grade (−0.204, p = 0.053). Differences in radiographic measures between HV line drawing grades were significant for intermetatarsal (F = 13.98, p < 0.001) hallux abductus (F = 38.90, p < 0.001) but not hallux interphalangeal abductus angle (F = 2.21, p = 0.075).ConclusionGrading HV severity by self‐reported HV line‐drawings provides a valid representation of deformity determined from radiographic measurements and is a useful screening/self‐reporting tool.
Structured presurgery prehabilitation for aged patients undergoing elective surgery significantly improves surgical outcomes and reduces cost: A nonrandomized sequential comparative prospective cohort study
Authors: Koh Frederick H. , Loh Caroline H. , Tan Winson J. , Ho Leonard M.L. , Yen Dulcena , Chua Jason M.W. , Kok Shawn S.X. , Sivarajah Sharmini S. , Chew Min‐Hoe , Foo Fung‐Joon 
Published: December 2021

AbstractBackgroundWith increasing global life expectancy, the number of major surgeries performed on aged adults invariably increases. This study aimed to examine the effectiveness of a structured prehabilitative program for aged colorectal cancer patients in improving short‐term surgical outcomes.MethodsA prospective philanthropically sponsored Programme for Enhanced Elderly Recovery at Sengkang General Hospital (PEERS) was initiated in February 2017 for patients ≥70‐years‐old who were due to undergo elective colectomies. These patients were put through a 2‐ to 4‐week‐long program before surgery, which included geriatric assessment, nutrition supplementation, and resistance training. They were compared with patients from a similar age group before PEERS was introduced (non‐PEERS).ResultsFifty‐eight patients, with a median age of 78.5 (70–93) years, were recruited from a single institution to undergo PEERS. Baseline characteristics between the groups were similar. There was no significant improvement of anthropometric and functional characteristics before and after PEERS. Duration of hospitalization was shorter in the PEERS group (9 vs 11 days, P = 0.01). Both groups had similar 30‐days’ morbidity rates (8.6% vs 17.4%, P = 0.26). The PEERS group had significant improvement in their median EuroQol‐5 Dimension score (0.70 presurgery to 0.80 6‐months’ postsurgery, P = 0.01). After multivariate analysis, the average duration of hospitalization in the PEERS group was 6.8 days shorter (P = 0.018; CI, 1.2–12.4) after adjusting for modality of surgery and complications. This represented a cost saving of USD$11,838.80.ConclusionA standardized prehabilitation program for aged adults reduced the duration of hospitalization, improved the quality of life after surgery, and reduced costs.
Translation, validity, and reliability of NUTRISCORE: The nutrition risk assessment screening test for Turkish cancer patients
Authors: Ak Elif , Demirel Birsen , Atasoy Beste M. , Yumuk Perran Fulden 
Published: December 2021

AbstractPurposeThe aim was to determine the validity and the reliability of the Turkish version of the screening test named NUTRISCORE in cancer patients.MethodsThe language validity of the Turkish form of the study scale was provided by the translationback‐translation method. NUTRISCORE and nutritional risk screening (NRS)‐2002, malnutrition screening tool (MST), and European Diagnostic Criteria (EDC) were administered to 240 volunteers in oncology clinics, and receiver operating characteristic curves (ROC) were calculated for the validity and reliability analysis. Cohen's kappa coefficient was used to determine the fit between the screening tests.ResultsThirteen experts were consulted for scale content validity, and the content validity index was found to be 0.94. The scale was administered to 67 patients with 4‐week intervals for test‐retest reliability, and a positive, high‐level and statistically significant relationship was found between the two measurements (r = 0.971, P < 0.01). Compared with the reference test NRS‐2002, the specificity values of NUTRISCORE, MST, and EDC screening tests were found to be 100%, 83%, and 91%, whereas the sensitivity values of same screening tests were calculated as 85%, 91% and 81%, respectively. According to Cohen's kappa statistics, the kappa agreement between NRS‐2002 and NUTRISCORE was 0.88, the kappa agreement between NRS‐2002 and MST was 0.34, and it was found to be 0.73 for NRS‐2002 and EDC.ConclusionThe nutrition screening test named NUTRISCORE showed adequate validity and reliability in Turkish and can detect malnutrition risk of cancer patients treated in oncology clinics as a screening tool.
Exploring the role of charitable ethnocentrism and donation motives in international giving: Empirical evidence from Germany
Authors: Müller Marcella S. , Lindenmeier Jörg 
Published: December 2021

AbstractThe purpose of this study is to contribute to a better understanding of the drivers of international giving intention by examining the joint effect of ethnocentrism and donation motives. More specifically, this study analyzes the direct effect of charitable ethnocentrism on the intention to give to international causes. Additionally, the study investigates the moderating effect of charitable ethnocentrism on the relationships between donation motives and the intention to donate to international causes. This study's findings indicate that ethnocentric donors are less willing to donate to international causes. Moreover, the study results show that the effects of egoistic and tax‐saving donation motives vary across different levels of charitable ethnocentrism: charitable ethnocentrism enhances the effect of the egoism motive on international donation intention, whereas the effect of the tax‐saving motive on international giving intention is mitigated. Based on the empirical findings, this study discusses implications for theory and practice along with study limitations and avenues for future research.
Indoleamine 2,3‐dioxygenase (IDO)‐1 and IDO‐2 activity and severe course of COVID‐19
Authors: Guo Lihui , Schurink Bernadette , Roos Eva , Nossent Esther J , Duitman Jan Willem , Vlaar Alexander PJ , van der Valk Paul , Vaz Frédéric M , Yeh Syun‐Ru , Geeraerts Zachary , Dijkhuis Annemiek , van Vught Lonneke , Bugiani Marianna , Lutter René ,   also on behalf of the Amsterdam UMC COVID‐19 Biobank Study Group
Published: December 2021

AbstractCOVID‐19 is a pandemic with high morbidity and mortality. In an autopsy cohort of COVID‐19 patients, we found extensive accumulation of the tryptophan degradation products 3‐hydroxy‐anthranilic acid and quinolinic acid in the lungs, heart, and brain. This was not related to the expression of the tryptophan‐catabolizing indoleamine 2,3‐dioxygenase (IDO)‐1, but rather to that of its isoform IDO‐2, which otherwise is expressed rarely. Bioavailability of tryptophan is an absolute requirement for proper cell functioning and synthesis of hormones, whereas its degradation products can cause cell death. Markers of apoptosis and severe cellular stress were associated with IDO‐2 expression in large areas of lung and heart tissue, whereas affected areas in brain were more restricted. Analyses of tissue, cerebrospinal fluid, and sequential plasma samples indicate early initiation of the kynurenine/aryl‐hydrocarbon receptor/IDO‐2 axis as a positive feedback loop, potentially leading to severe COVID‐19 pathology. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Pancancer cytotoxic T‐cell trapping: are neutrophil extracellular traps a viable biomarker for immunotherapy response?†
Authors: Desharnais Lysanne , D Spicer Jonathan 
Published: December 2021

AbstractIn a recent issue of The Journal of Pathology, a study by de Andrea, Ochoa, Villalba‐Esparza et al demonstrated the presence of neutrophil extracellular traps (NETs) in a variety of human solid tumor types detected by multiplex immunofluorescence. In addition to NET identification and quantification, they found that there is individual heterogeneity in NET abundance in tumors and in circulation, and that NETs are positively associated with IL‐8 and negatively associated with tumor‐infiltrating CD8+ T cells. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Health‐related quality of life, obesity, fragmented sleep, fatigue, and psychosocial problems among youth with craniopharyngioma
Authors: Klages Kimberly L. , Berlin Kristoffer S. , Cook Jessica L. , Merchant Thomas E. , Wise Merrill S. , Mandrell Belinda N. , Conklin Heather M. , Crabtree Valerie McLaughlin 
Published: December 2021

AbstractObjectiveYouth with craniopharyngioma experience weight gain, fragmented sleep, excessive daytime sleepiness (EDS), fatigue, and psychosocial problems that negatively impact their overall health‐related quality of life (HRQoL). Greater hypothalamic tumor involvement (HI) may be associated with higher rates or severity of these impairments; however, the direct and indirect impact of HI on the physical and psychosocial consequences associated with pediatric craniopharyngioma remain unclear. The purpose of the current study was to examine relations between HI, body mass index (BMI), fragmented sleep, EDS, fatigue, psychosocial problems, and HRQoL among youth with craniopharyngioma.MethodsEighty‐four youth with craniopharyngioma (Mage = 10.27 ± 4.3 years, 53.6% female, 64.3% White) were assessed with actigraphy, nocturnal polysomnography, and multiple sleep latency tests prior to proton therapy, when indicated. Caregivers completed measures of fatigue, psychosocial functioning, and HRQoL.ResultsHypothalamic tumor involvement was associated with greater BMI (Est. = 2.97, p = 0.003) and daytime sleepiness (Est. = 2.53, p = 0.01). Greater fatigue predicted more psychosocial problems (Est. = 0.29, p < 0.001) and lower HRQoL (Est. = 0.23, p = 0.001). Psychosocial problems also predicted lower HRQoL (Est. = −0.34, p = 0.004). Fragmented sleep (Est. = 0.03, p = 0.04) and fatigue (Est. = 0.10, p = 0.02) indirectly predicted lower HRQoL through psychosocial problems.ConclusionsYouth with craniopharyngioma with greater HI may benefit from weight reduction interventions and management of excessive sleepiness. Patients should be prospectively monitored for sleep problems, fatigue, and psychosocial problems, as these patients may benefit from interventions targeting fatigue and psychosocial health to improve HRQoL.
One‐Pot Synthesis and DFT Calculations of Ti‐BiOCl/Bi Heterostructure Photocatalyst with Oxygen Vacancies and Bi Metal Induced by Ti Doping
Authors: Li Danyang , Wu Chuanrui , Wen Xiaoxu , Gao Bo , Liu Ziyi , Huang Haihua , Yao Shujuan , Pu Xipeng 
Published: December 2021

AbstractOxygen vacancies (OVs), doped Ti and plasmonic Bi metal are simultaneously introduced into BiOCl, which is prepared by a simple and one‐pot solvothermal method without any special reduction and high‐temperature processes. The microstructures, electronic structures, optical properties, and photodegradation activity are systematically discussed. Additionally, the amount of attached Bi metal and photocatalytic efficiency can be tuned via the content of doped Ti. The ultrahigh electron transfer tunnel between intermediate energy levels and attached Bi metals is confirmed through the close combination of active species detection experiments and density functional theory calculations. Further, the enhanced photocatalysis mechanism is discussed in detail. In the current study, the prospective on the preparation methods and modification strategies involving OVs, attached plasmonic Bi metal, and doped metal could be extended to other catalysts to regulate their interfacial properties and catalytic activity to deal with environmental problems.
Wool fiber curvature is correlated with abundance of K38 and specific keratin‐associated proteins
Authors: Plowman Jeffrey E. , Harland Duane P. , Richena Marina , Thomas Ancy , Hefer Charles A. , van Koten Chikako , Scobie David R. , Grosvenor Anita J. 
Published: December 2021

AbstractCurvature in mammalian fibers, such as wool and human hair, is an important feature of the functional trait of coat structure—it affects mechanical resilience and thermo‐insulation. However, to examine the relationship between fiber curvature, ultrastructure and protein composition fiber diameter variability has to be minimal. To achieve this we utilised the progeny of straight‐wool domestic sheep mutant rams (crimp mutants) and wild‐type ewes. Proteomic and structural results of the resulting mutant/wild‐type twin pairs confirmed that straight crimp mutant wool had a normal cuticle and the same cortical protein and ultrastructural building blocks as wild‐type (crimpy) fibers but differed in the layout of its cortical cells and in the relative proportions of keratin (K) and keratin‐associated proteins (KAPs). In the case of the crimp mutants (straight fibers), the orthocortex was distributed in a fragmented, annular ring, with some orthocortical cells near the central medulla, a pattern similar to that of straight hairs from humans and other mammals. Crimp mutant fibers were noted for the reduced abundance of some proteins in the high glycine–tyrosine class normally associated with the orthocortex, specifically the KAP6, KAP7, and KAP8 families, while proteins from the KAP16 and KAP19 were found in increased abundance. In addition to this, the type I keratin, K38, which is also associated with the orthocortex, was also found at lower abundance in the mutant fibers. Conversely, proteins from the ultra‐high sulfur class normally associated with the paracortex, specifically the KAP4 and KAP9 families, were found in higher abundance.
Adjusting for bias in the mean for primary and secondary outcomes when trials are in sequence
Authors: Rothwell Joanne C. , Julious Steven A. , Cooper Cindy L. 
Published: December 2021

AbstractWhen designing a clinical trial, one key aspect of the design is the sample size calculation. The sample size calculation tends to rely on a target or expected difference. The expected difference can be based on the observed data from previous studies, which results in bias. It has been reported that large treatment effects observed in trials are often not replicated in subsequent trials. If these values are used to design subsequent studies, the sample sizes may be biased which results in an unethical study. Regression to the mean (RTM) is one explanation for this. If only health technologies which meet a particular continuation criterion (such as in the first study) are progressed to a second confirmatory trial, it is highly likely that the observed effect in the second trial will be lower than that observed in the first trial. It will be shown how when moving from one trial to the next, a truncated normal distribution is inherently imposed on the first study. This results in a lower observed effect size in the second trial. A simple adjustment method is proposed based on the mathematical properties of the truncated normal distribution. This adjustment method was confirmed using simulations in R and compared with other previous adjustments. The method can be applied to the observed effect in a trial, which is being used in the design of a second confirmatory trial, resulting in a more stable estimate for the ‘true’ treatment effect. The adjustment accounts for the bias in the primary and secondary endpoints in the first trial with the bias being affected by the power of that study. Tables of results have been provided to aid implementation, along with a worked example. In summary, there is a bias introduced when the point estimate from one trial is used to assist the design of a second trial. It is recommended that any observed point estimates be used with caution and the adjustment method developed in this article be implemented to significantly reduce this bias.