bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospitalizations in solid tumor phase I clinical trial patients: Incidence, pattern and clinical outcomes at an Australian phase I clinical trial unit
Authors: Ye Linda , Ariyapperuma Mihitha , Jacques Angela , Meniawy Tarek , Millward Michael 
Published: June 2021

AbstractBackgroundParticipation in early‐phase clinical trials has become a prominent part of medical oncology patient management. We examined the incidence and pattern of hospitalizations in early‐phase clinical trial patients and the associated clinical outcomes.MethodWe conducted a retrospective review of 194 patients with solid tumors treated on phase I clinical trials between July 2014 and October 2018 at a phase I trial unit. Unplanned hospitalizations occurring during the study period were characterized and correlated with treatment response and duration of trial participation.ResultsAmong 194 patients, 104 hospitalizations were recorded involving 62 patients (31%). Nineteen percent of patients were hospitalized for cancer‐related complications and 8% for treatment toxicity. No significant correlation was seen between the hospitalization and age, sex, tumor type, or trial drug. Best response to trial therapy was complete response, partial response, stable disease, and progressive disease in 5%, 11%, 37%, and 47% of patients, respectively. Median duration on trial was 86 days (range 0–1,412). Twenty‐two patients (11%) remained on trial for more than 12 months. Overall, hospitalization did not impact treatment response or trial duration. However, cancer‐related hospitalization was associated with significantly lower response (p < 0.001) and early patient attrition (p < 0.001). Resolution of the hospitalization event was associated with improved response (p = 0.002) and longer duration on trial (p < 0.001). The treatment related mortality was 0.5% (n = 1).ConclusionApproximately one third of patients required hospitalization, most commonly for cancer‐related complications which correlated with poorer clinical outcomes. Hospitalizations related to treatment toxicity were infrequent. A significant proportion of patients derived significant therapeutic benefit. Phase I clinical trials provide a valuable treatment option for patients with cancer.
One Health: EAACI Position Paper on coronaviruses at the human‐animal interface, with a specific focus on comparative and zoonotic aspects of SARS‐CoV‐2
Authors: Korath Anna D. J. , Janda Jozef , Untersmayr Eva , Sokolowska Milena , Feleszko Wojciech , Agache Ioana , Adel Seida Ahmed , Hartmann Katrin , Jensen‐Jarolim Erika , Pali‐Schöll Isabella 
Published: June 2021

AbstractThe latest outbreak of a coronavirus disease in 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), evolved into a worldwide pandemic with massive effects on health, quality of life, and economy. Given the short period of time since the outbreak, there are several knowledge gaps on the comparative and zoonotic aspects of this new virus. Within the One Health concept, the current EAACI position paper dwells into the current knowledge on SARS‐CoV‐2’s receptors, symptoms, transmission routes for human and animals living in close vicinity to each other, usefulness of animal models to study this disease and management options to avoid intra‐ and interspecies transmission. Similar pandemics might appear unexpectedly and more frequently in the near future due to climate change, consumption of exotic foods and drinks, globe‐trotter travel possibilities, the growing world population, the decreasing production space, declining room for wildlife and free‐ranging animals, and the changed lifestyle including living very close to animals. Therefore, both the society and the health authorities need to be aware and well prepared for similar future situations, and research needs to focus on prevention and fast development of treatment options (medications, vaccines).
Endoscopic clips allow for accurate pre‐operative localisation of colorectal cancer
Authors: Parys Simon , Park Hyerin , Entriken Fiona , Ee Hooi C. , Hodder Rupert 
Published: June 2021

AbstractBackgroundColorectal cancer is a major cause of morbidity and mortality worldwide. Optimal management of this disease relies upon accurate pre‐operative localisation to allow multidisciplinary discussion and treatment planning. Current pre‐operative localisation methods consist of colonoscopy and computed tomography (CT), which are only 79%–85% accurate. To minimise this error, colonoscopy tattooing is a routine practice to facilitate operative localisation. The aim of this study is to investigate if endoscopic radiopaque clips can more accurately localise the lesions pre‐operatively.MethodsA retrospective case–control study was conducted of patients diagnosed with colorectal cancer at a tertiary hospital between 2017 and 2019. Visualisation rates and accurate localisation rates were compared between patients receiving radiopaque clips and those who had colonoscopy alone. All patients received a tattoo distal to the tumour and a staging CT. Data on patient demographics, tumour demographics, post‐procedure complications and changes to surgical management were collected.ResultsOf 285 patients, 245 had tumour localisation with colonoscopy alone and 40 had additional clip localisation. Groups had comparable patient demographics. For patients receiving clips and follow‐up CTs within 14 days, 92% of lesions were visualised and 100% of these lesions were accurately localised. In contrast, colonoscopy only accurately localised 77% of lesions (p < 0.01). This resulted in 1.2% of patients requiring an altered operation due to incorrect localisation. No clip‐related complications were reported.ConclusionRadiopaque clips are a highly accurate and cost‐effective method for localising colorectal cancer with a pre‐operative accuracy rate over 92%.
Prevalence and incidence of diabetic retinopathy (DR) in the UK population of Gloucestershire
Authors: Scanlon Peter H. , Nevill Clareece R. , Stratton Irene M. , Maruti Sonia S. , Massó‐González Elvira L. , Sivaprasad Sobha , Bailey Clare , Ehrlich Michael , Chong Victor 
Published: June 2021

AbstractPurposeTo estimate prevalence and incidence of diabetic retinopathy (DR) in a UK region by severity between 2012 and 2016 and risk factors for progression to proliferative DR (PDR).MethodsElectronic medical records from people with diabetes (PWD) ≥18 years seen at the Gloucestershire Diabetic Eye Screening Programme (GDESP) and the hospital eye clinic were analysed (HEC). Prevalence and incidence of DR per 100 PWD (%) by calendar year, grade and diabetes type were estimated using log‐linear regression. Progression to PDR and associated risk factors were estimated using parametric survival analyses.ResultsAcross the study period, 35 873 PWD had at least one DR assessment. They were aged 66 (56–75) years (median (interquartile range)), 57% male, 5 (1–10) years since diabetes diagnosis, 93% Type 2 diabetes. Prevalence of DR decreased from 38.9% (95% CI: 38.1%, 39.8%) in 2012 to 36.6% (95% CI: 35.9%, 37.3%) in 2016 (p < 0.001). Incidence of any DR decreased from 10.9% (95% CI: 10.4%, 11.5%) in 2013 to 8.5% (95% CI: 8.1%, 9.0%) in 2016 (p < 0.001). Prevalence of PDR decreased from 3.5% (95% CI: 3.3%, 3.8%) in 2012 to 3.1% (95% CI 2.9%, 3.3%) in 2016 (p = 0.008). Incidence of PDR did not change over time. HbA1c and bilateral moderate–severe NPDR were statistically significant risk factors associated with progression to PDR.ConclusionsIncidence and prevalence of DR decreased between 2012 and 2016 in this well‐characterized population of the UK.
Recognizing heat‐treated chert: A comparison between infrared spectroscopy and fracture surface analysis
Authors: Bachellerie Julie , Schmidt Patrick 
Published: June 2021

AbstractHeat treatment of lithic raw material is used for the first time in Europe in the Solutrean of the upper Paleolithic. The study of which heating technique was used by these groups requires analytical methods to understand and recognize the chemical and physical processes involved. Roughness measurements were tested as a tool for recognizing heat treatment and to compare them to infrared spectroscopy. We also measured the surface topography of geological samples to observe its evolution as a function of heating and then compare the results with those obtained on Solutrean artefacts. Near infrared analyses was carried out for comparing the effectiveness of surface roughness measurements. This work complements our knowledge about the heating environment used by Solutrean groups by confirming the use of controlled heating. In addition, our roughness measurements provide promising results for the recognition of heat treatment through the quantification of the surface luster.
Justifying the risks of COVID‐19 challenge trials: The analogy with organ donation
Authors: Jayaram Athmeya , Sparks Jacob , Callies Daniel 
Published: June 2021

AbstractIn the beginning of the COVID pandemic, researchers and bioethicists called for human challenge trials to hasten the development of a vaccine for COVID. However, the fact that we lacked a specific, highly effective treatment for COVID led many to argue that a COVID challenge trial would be unethical and we ought to pursue traditional phase III testing instead. These ethical objections to challenge trials may have slowed the progress of a COVID vaccine, so it is important to evaluate their merit. One common way of doing so is to make an analogy to other social practices that are relevantly similar and which we currently sanction. We submit that non‐directed live organ donation (NDLOD) is a promising analogy. After arguing that the risks to volunteers for each activity appear similar, we explore potential disanalogies that would undermine the comparison. We note that there are differences in both the kind and certainty of benefit secured by NDLOD compared to challenge trials. We conclude these differences are insufficient to make NDLOD permissible and challenge trials impermissible. Ultimately, if we think the risks associated with NDLOD are ethically permissible, then we should think the same of the risks associated with COVID challenge trials.
Australian women's experiences of receiving maternity care during the COVID‐19 pandemic: A cross‐sectional national survey
Authors: Wilson Alyce N. , Sweet Linda , Vasilevski Vidanka , Hauck Yvonne , Wynter Karen , Kuliukas Lesley , Szabo Rebecca A. , Homer Caroline S. E. , Bradfield Zoe 
Published: June 2021

AbstractBackgroundThe COVID‐19 pandemic has led to multiple changes in maternity services worldwide. Systems rapidly adapted to meet public health requirements aimed at preventing transmission of SARS‐CoV‐2, including quarantine procedures, travel restrictions, border closures, physical distancing and “stay‐at‐home” orders. Although these changes have impacted all stakeholders in maternity services, arguably the women at the center of this care have been most affected. This study aimed to explore women's experiences of receiving maternity care during the COVID‐19 pandemic in Australia.MethodsA national cross‐sectional online survey, including fixed choice and open‐ended questions, was conducted during the first wave of the COVID‐19 pandemic in Australia; pregnant and postnatal women were recruited through social media networks.ResultsThe survey was completed by 3364 women. Women felt distressed and alone due to rapid changes to their maternity care. Limited face‐to‐face contact with health practitioners and altered models of care often required women to accommodate significant changes and to coordinate their own care. Women felt that they were often “doing it alone,” due to public health restrictions on support people and visitors, both within and outside health services. Women described some benefits of visitor restrictions, such as, more time for rest, breastfeeding establishment, and bonding with their baby.ConclusionsThis large nationwide Australian study provides unique data on women's experiences of receiving maternity care during the COVID‐19 pandemic. Lessons learned provide an opportunity to rebuild and reshape the maternity sector to best meet the needs of women and their families during current and future public health crises.
Predictors of cardiovascular events and all‐cause of death in patients with transfusion‐dependent myelodysplastic syndrome
Authors: Alonso‐Fernandez‐Gatta Marta , Martin‐Garcia Ana , Martin‐Garcia Agustin C. , Lopez‐Cadenas Felix , Diaz‐Pelaez Elena , Jimenez‐Solas Tamara , Gonzalez‐Martinez Teresa , Sanchez‐Pablo Clara , Diez‐Campelo Maria , Sanchez Pedro L. 
Published: June 2021

SummaryCardiovascular disease (CVD) involves the second cause of death in low‐risk myelodysplastic syndrome (MDS) population. Prospective study to characterise the CVD and to identify predictors for the combined event (CE) cardiovascular event and/or all‐cause mortality in transfusion dependent low‐risk MDS patients. Thirty‐one patients underwent a cardiac assessment including biomarkers and cardiac magnetic resonance (cMR) with parametric sequences (T1, T2 and T2* mapping) and myocardial deformation by feature tracking (FT) and were analysed for clonal hematopoiesis of indeterminate potential mutations. Cardiac assessment revealed high prevalence of unknown structural heart disease (51% cMR pathological findings). After 2·2 [0·44] years follow‐up, 35·5% of patients suffered the CE: 16% death, 29% cardiovascular event. At multivariate analysis elevated NT‐proBNP ≥ 486pg/ml (HR 96·7; 95%‐CI 1·135–8243; P = 0·044), reduced native T1 time < 983ms (HR 44·8; 95%‐CI 1·235–1623; P = 0·038) and higher left ventricular global longitudinal strain (LV‐GLS) (HR 0·4; 95%‐CI 0·196–0·973; P = 0·043) showed an independent prognostic value. These variables, together with the myocardial T2* time < 20ms, showed an additive prognostic value (Log Rank: 12·4; P = 0·001). In conclusion, low‐risk MDS patients frequently suffer CVD. NT‐proBNP value, native T1 relaxation time and longitudinal strain by FT are independent predictors of poor cardiovascular prognosis, thus, their determination would identify high‐risk patients who could benefit from a cardiac treatment and follow‐up.
Grassland trees and the common bulbul Pycnonotus barbatus promote Afromontane forest restoration
Authors: Jaafar Ridwan , Yadok Biplang G. , Elisha Emmanuel B. , Chapman Hazel M. 
Published: June 2021

AbstractRestoration of Afromontane forests is critical because of their biodiversity richness and ecosystem service provision. With an evolutionary history of rapid forest migration into grassland in response to shifting climate, traits of Afromontane forests such as a high frequency of light tolerant, small fruited, and bird dispersed species may pre‐adapt them to relatively rapid recolonization of grassland protected from fire. Here, we test this hypothesis with a focus on the role of isolated grassland tree species in promoting forest regeneration. Through seed, seedling, and frugivore surveys, we found that seed rain below small, isolated grassland trees was almost 300 times that in open grassland, with 30 times more seedlings established under trees. However, these seedlings were mostly grassland or forest edge woody shrubs or small trees. Dispersal limitation was moderate to high and establishment limitation high for all other species. Ecological filtering of seed species favored some over others, which needs further exploration. Key tree traits attracting frugivore visits were distance from forest edge, height, and “leaflessness.” Across a year of sampling almost 90% of frugivore visits to isolated trees were by just two grassland / forest edge species, the common bulbul Pycnonotus barbatus (71%) and the speckled mouse bird Colius striatus (17%). Overall, our results suggest that while anthropogenic changes within Afromontane systems render any pre‐adaption Afromontane forests may have to rapid reestablishment of forest into grassland ineffectual, small, isolated grassland trees are nevertheless critical for the first stage of succession.
Ca2+‐activated K+ channel KCa1.1 as a therapeutic target to overcome chemoresistance in three‐dimensional sarcoma spheroid models
Authors: Ohya Susumu , Kajikuri Junko , Endo Kyoko , Kito Hiroaki , Elboray Elghareeb E. , Suzuki Takayoshi 
Published: June 2021

AbstractThe large‐conductance Ca2+‐activated K+ channel KCa1.1 plays a pivotal role in tumor development and progression in several solid cancers. The three‐dimensional (3D) in vitro cell culture system is a powerful tool for cancer spheroid formation, and mimics in vivo solid tumor resistance to chemotherapy in the tumor microenvironment (TME). KCa1.1 is functionally expressed in osteosarcoma and chondrosarcoma cell lines. KCa1.1 activator‐induced hyperpolarizing responses were significantly larger in human osteosarcoma MG‐63 cells isolated from 3D spheroid models compared with in those from adherent 2D monolayer cells. The present study investigated the mechanisms underlying the upregulation of KCa1.1 and its role in chemoresistance using a 3D spheroid model. KCa1.1 protein expression levels were significantly elevated in the lipid‐raft‐enriched compartments of MG‐63 spheroids without changes in its transcriptional level. 3D spheroid formation downregulated the expression of the ubiquitin E3 ligase FBXW7, which is an essential contributor to KCa1.1 protein degradation in breast cancer. The siRNA‐mediated inhibition of FBXW7 in MG‐63 cells from 2D monolayers upregulated KCa1.1 protein expression. Furthermore, a treatment with a potent and selective KCa1.1 inhibitor overcame the chemoresistance of the MG‐63 and human chondrosarcoma SW‐1353 spheroid models to paclitaxel, doxorubicin, and cisplatin. Among several multidrug resistance ATP‐binding cassette transporters, the expression of the multidrug resistance‐associated protein MRP1 was upregulated in both spheroids and restored by the inhibition of KCa1.1. Therefore, the pharmacological inhibition of KCa1.1 may be an attractive new strategy for acquiring resistance to chemotherapeutic drugs in the TME of KCa1.1‐positive sarcomas.
The Warburg effect as a therapeutic target for bladder cancers and intratumoral heterogeneity in associated molecular targets
Authors: Burns Julie E. , Hurst Carolyn D. , Knowles Margaret A. , Phillips Roger M. , Allison Simon J. 
Published: June 2021

AbstractBladder cancer is the 10th most common cancer worldwide. For muscle‐invasive bladder cancer (MIBC), treatment includes radical cystectomy, radiotherapy, and chemotherapy; however, the outcome is generally poor. For non–muscle‐invasive bladder cancer (NMIBC), tumor recurrence is common. There is an urgent need for more effective and less harmful therapeutic approaches. Here, bladder cancer cell metabolic reprogramming to rely on aerobic glycolysis (the Warburg effect) and expression of associated molecular therapeutic targets by bladder cancer cells of different stages and grades, and in freshly resected clinical tissue, is investigated. Importantly, analyses indicate that the Warburg effect is a feature of both NMIBCs and MIBCs. In two in vitro inducible epithelial‐mesenchymal transition (EMT) bladder cancer models, EMT stimulation correlated with increased lactate production, the end product of aerobic glycolysis. Protein levels of lactate dehydrogenase A (LDH‐A), which promotes pyruvate enzymatic reduction to lactate, were higher in most bladder cancer cell lines (compared with LDH‐B, which catalyzes the reverse reaction), but the levels did not closely correlate with aerobic glycolysis rates. Although LDH‐A is expressed in normal urothelial cells, LDH‐A knockdown by RNAi selectively induced urothelial cancer cell apoptotic death, whereas normal cells were unaffected—identifying LDH‐A as a cancer‐selective therapeutic target for bladder cancers. LDH‐A and other potential therapeutic targets (MCT4 and GLUT1) were expressed in patient clinical specimens; however, positive staining varied in different areas of sections and with distance from a blood vessel. This intratumoral heterogeneity has important therapeutic implications and indicates the possibility of tumor cell metabolic coupling.
‘We are Hungry but We Won’t Eat the Food’: Schoolchildren’s ‘Thin’ agency and its impacts on the implementation of Ghana’s School Feeding Programme
Authors: Mohammed Abdul‐Rahim 
Published: June 2021

AbstractFollowing the introduction of the concept of agency by the New Sociology of Childhood, the concept has dominated discourses about children's everyday lives. Nevertheless, little is known about schoolchildren's agency in their daily interactions with the service providers of Ghana's school feeding programme. Through this qualitative study, the paper provides empirical evidence to show how children in restrictive contexts exercise ‘thin’ agency in their interactions with frontline service providers, leading to significant improvements in the quality of services delivered to them. Consequently, the article questions Michael Lipsky's assumption that clients have minimal effect on the services delivered to them.
Disclosures of harming others during their most recent drinking session: Findings from a large national study of heavy‐drinking adolescents
Authors: Lam Tina , Laslett Anne‐Marie , Fischer Jane , Salom Caroline , Ogeil Rowan P. , Lubman Dan I. , Aiken Alexandra , Mattick Richard , Gilmore William , Allsop Steve 
Published: June 2021

AbstractIntroductionThe extant Alcohol's Harms to Others (AHTO) literature is largely comprised of reports from victims. We investigated AHTO from perpetrators' perspectives, including how harms were associated with individual characteristics, and alcohol quantities consumed during the perpetration incident.MethodsParticipants (N = 2932) were 14–19 years old, recruited primarily through social media and screened as risky drinkers. They completed face‐to‐face (n = 594) or self‐administered (n = 2338) surveys. They self‐reported whether during their last risky drinking session (LRDS) they had perpetrated any verbal abuse, physical abuse or property damage. A multinomial logistic regression examined whether nine factors were associated with perpetrating zero, one or 2+ categories of AHTO.ResultsEleven percent (n = 323) reported perpetrating at least one form of AHTO (7.5% verbal, 1.9% physical and 4.6% property). Perpetration of AHTO at LRDS was uniquely associated with: younger age, male gender, experiences of childhood physical punishment, greater perpetration incident‐specific drinking, concurrent illicit drug use, and less frequent use of safety strategies while drinking in the past 12 months. Controlling for the other variables, an increase of six Australian standard drinks (60 g of alcohol) increased the odds of perpetration by 15% [95% confidence interval (CI) adjusted odds ratio (AOR) 1.08, 1.23], and an increase of 15 Australian standard drinks increased the odds by 42% (95% CI AOR 1.20, 1.69).Discussion and ConclusionsIndividual characteristics, larger quantities of alcohol consumed, and a disinclination to practice harm reduction amplified risk of AHTO perpetration. This has implications for health promotion and risk prevention/reduction strategies.