bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical usefulness of prediction tools to identify adult hospitalized patients at risk of drug‐related problems: A systematic review of clinical prediction models and risk assessment tools
Authors: Deawjaroen Kulchalee , Sillabutra Jutatip , Poolsup Nalinee , Stewart Derek , Suksomboon Naeti 
Published: October 2021

AimsThis study aimed to review systematically all available prediction tools identifying adult hospitalized patients at risk of drug‐related problems, and to synthesize the evidence on performance and clinical usefulness.MethodsPubMed, Scopus, Web of Science, Embase, and CINAHL databases were searched for relevant studies. Titles, abstracts and full‐text studies were sequentially screened for inclusion by two independent reviewers. The Prediction Model Risk of Bias Assessment Tool (PROBAST) and the Revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) checklists were used to assess risk of bias and applicability of prediction tools. A narrative synthesis was performed.ResultsA total of 21 studies were included, 14 of which described the development of new prediction tools (four risk assessment tools and ten clinical prediction models) and six studies were validation based and one an impact study. There were variations in tool development processes, outcome measures and included predictors. Overall, tool performance had limitations in reporting and consistency, with the discriminatory ability based on area under the curve receiver operating characteristics (AUROC) ranging from poor to good (0.62–0.81), sensitivity and specificity ranging from 57.0% to 89.9% and 30.2% to 88.0%, respectively. The Medicines Optimisation Assessment tool and Assessment of Risk tool were prediction tools with the lowest risk of bias and low concern for applicability. Studies reporting external validation and impact on patient outcomes were scarce.ConclusionMost prediction tools have limitations in development and validation processes, as well as scarce evidence of clinical usefulness. Future studies should attempt to either refine currently available tools or apply a rigorous process capturing evidence of acceptance, usefulness, performance and outcomes.
Don’t put all your green eggs in one basket: Examining environmentally friendly sub‐branding strategies
Authors: Koo Jayoung , Loken Barbara 
Published: October 2021

AbstractAlthough marketers are increasingly developing strategies to promote environmentally‐friendly images for their brands, little is known about green brand architecture strategies. The current study examines two sub‐branding strategies and finds that when green products are dispersed across several sub‐brands (vs. concentrated within one sub‐brand), consumers are more likely to infer that the overall parent brand is environmentally friendly. The sincerity of the company’s sustainability efforts is found to mediate the effects of the sub‐branding strategy on consumers’ eco‐friendly beliefs of the parent brand. Specifically, consumers associate dispersed strategy (vs. concentrated strategy) with intrinsic motive (vs. extrinsic motive) of the company’s sustainability policy. As a result, dispersed strategy instead of concentrated strategy promotes spillover effects of sustainability to the parent brand, demonstrating the impact of brand structure on spillover to the parent brand equity. Managerial implications are discussed related to the automobile company’s sub‐branding strategy.
Epstein–Barr virus status of sporadic Burkitt lymphoma is associated with patient age and mutational features
Authors: Richter Julia , John Katharina , Staiger Annette M. , Rosenwald Andreas , Kurz Katrin , Michgehl Ulf , Ott German , Franzenburg Sören , Kohler Christian , Finger Jasmin , Oschlies Ilske , Paul Ulrike , Siebert Reiner , Spang Rainer , Burkhardt Birgit , Klapper Wolfram 
Published: October 2021

SummarySporadic Burkitt lymphoma (BL) is the most frequent tumour of children and adolescents but a rare subtype of lymphomas in adults. To date most molecular data have been obtained from lymphomas arising in the young. Recently, Epstein–Barr virus (EBV) positive and negative BL in young patients was shown to differ in molecular features. In the present study, we present a large age‐overarching cohort of sporadic BL (n = 162) analysed by immunohistochemistry, translocations of MYC proto‐oncogene, basic helix‐loop‐helix transcription factor (MYC), B‐cell leukaemia/lymphoma 2 (BCL2) and B‐cell leukaemia/lymphoma 6 (BCL6) and by targeted sequencing. We illustrate an age‐associated inter‐tumoral molecular heterogeneity in this disease. Mutations affecting inhibitor of DNA binding 3, HLH protein (ID3), transcription factor 3 (TCF3) and cyclin D3 (CCND3), which are highly recurrent in paediatric BL, and expression of sex determining region Y‐box transcription factor 11 (SOX11) declined with patient age at diagnosis (P = 0·0204 and P = 0·0197 respectively). In contrast, EBV was more frequently detected in adult patients (P = 0·0262). Irrespective of age, EBV‐positive sporadic BL showed significantly less frequent mutations in ID3/TCF3/CCND3 (P = 0·0088) but more often mutations of G protein subunit alpha 13 (GNA13; P = 0·0368) and forkhead box O1 (FOXO1; P = 0·0044) compared to EBV‐negative tumours. Our findings suggest that among sporadic BL an EBV‐positive subgroup of lymphomas increases with patient age that shows distinct pathogenic features reminiscent of EBV‐positive endemic BL.
An insight into cytotoxic activity of flavonoids and sesquiterpenoids from selected plants of Asteraceae species
Authors: Butala Sahil , Suvarna Vasanti , Mallya Rashmi , Khan Tabassum 
Published: October 2021

AbstractCancer continues to be a disease that is difficult to cure and the current therapeutic regimen is associated with severe side effects and the issue of emerging drug resistance. According to the World Health Organization fact sheet 2017, cancer is the second major cause of morbidity and death and a 70% rise in new cases is expected over the next 20 years. The quest for new anticancer chemical entities is a thrust area identified by many government agencies and industry research and development groups. Nature‐derived entities have played a very important role in therapeutics especially cancer Asteraceae is a large family consisting of around 1700 genera and more than 24,000 species. Several genera belonging to this family have ethnopharmacological uses such as cytotoxicity, antidiabetic, hepatoprotective and antioxidant. This review highlights the cytotoxic potential of structurally novel flavonoids and sesquiterpenes isolated from some selected species of Asteraceae plants native to Asia, Europe, parts of Africa and America. The existing literature suggests that sesquiterpenes and flavonoids from various species of Asteraceae represent a viable class of secondary metabolites with strong cytotoxic potential. These have demonstrated potent activity in cell cycle arrest, inhibition of neoangiogenesis and induction of apoptosis. The sesquiterpenoids exhibiting potent cytotoxic activity were found to contain an α‐ methylene‐butyrolactone conjugated with an exomethylene group and the flavonoids obtained from various plant species of Blumea suggest that a dihydroxy ring system present in structure is essential for activity. Most of the published literature contains in vitro data of extracts/secondary metabolites with very few in vivo studies. Additionally, there is dearth of knowledge on mechanisms of cytotoxic activity and molecular targets impacted by the active secondary metabolites. This review hopes to fuel interest in researchers to take up detailed investigations on these scaffolds that could contribute significantly as potential leads in anticancer drug development.
Climate adaptation of biodiversity conservation in managed forest landscapes
Authors: Hylander Kristoffer , Greiser Caroline , Christiansen Ditte M. , Koelemeijer Irena A. 
Published: October 2021

AbstractConservation of biodiversity in managed forest landscapes needs to be complemented with new approaches given the threat from rapid climate change. Most frameworks for adaptation of biodiversity conservation to climate change include two major strategies. The first is the resistance strategy, which focuses on actions to increase the capacity of species and communities to resist change. The second is the transformation strategy and includes actions that ease the transformation of communities to a set of species that are well adapted to the novel environmental conditions. We suggest a number of concrete actions policy makers and managers can take. Under the resistance strategy, five tools are introduced, including: identifying and protecting forest climate refugia with cold‐favored species; reducing the effects of drought by protecting the hydrological network; and actively removing competitors when they threaten cold‐favored species. Under the transformation strategy, we suggest three tools, including: enhancing conditions for forest species favored by the new climate, but currently disfavored by forest management, by planting them at suitable sites outside their main range; and increasing connectivity across the landscape to enhance the expansion of warm‐favored species to sites that have become suitable. Finally, we suggest applying a landscape perspective and simultaneously managing for both retreating and expanding species. The two different strategies (resistance and transformation) should be seen as complementary ways to maintain a rich biodiversity in future forest ecosystems.
Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy
Authors: Seervai Riyad N. H. , Cho Woo Cheal , Chu Emily Y. , Marques‐Piubelli Mario L. , Ledesma Debora A. , Richards Kristen , Heberton Meghan M. , Nelson Kelly C. , Nagarajan Priyadharsini , Torres‐Cabala Carlos A. , Prieto Victor G. , Curry Jonathan L. 
Published: October 2021

AbstractBackgroundAdvances in molecular biology and genetics have contributed to breakthrough treatments directed at specific pathways associated with the development of cancer. Small‐molecule inhibitors (Nibs) aimed at a variety of cellular pathways have been efficacious; however, they are associated with significant dermatologic toxicities.MethodsWe conducted a comprehensive review of dermatologic toxicities associated with Nibs categorized into the following five groups: (a) mitogen‐activated protein kinase; (b) growth factor/multi‐tyrosine kinase; (c) cell division/DNA repair; (d) signaling associated with myeloproliferative neoplasms; and (e) other signaling pathways. Prospective phase I, II, or III clinical trials, retrospective literature reviews, systematic reviews/meta‐analyses, and case reviews/reports were included for analysis.ResultsDermatologic toxicities reviewed were associated with every class of Nibs and ranged from mild to severe or life‐threatening adverse skin reactions. Inflammatory reactions manifesting as maculopapular, papulopustular/acneiform, and eczematous lesions were frequent types of dermatologic toxicities seen with Nibs. Squamous cell carcinoma with keratoacanthoma‐like features was associated with a subset of Nibs. Substantial overlap in dermatologic toxicities was found between Nibs.ConclusionsDermatologic toxicities from Nibs are diverse and may overlap between classes of Nibs. Recognition of the various types of toxicities from Nibs is critical for patient care in the era of “oncodermatology/dermatopathology.”
Current and future plant invasions in protected areas: Does clonality matter?
Authors: Wan Ji‐Zhong , Wang Chun‐Jing , Zimmermann Niklaus E. , Li Mai‐He , Pouteau Robin , Yu Fei‐Hai 
Published: October 2021

AbstractAimProtected areas (PAs) play an important role in biodiversity conservation, but remain increasingly threatened by invasive alien plant species (IAPS) in conjunction with global climate change. The latter is modifying the distribution of the former, and the magnitude and direction of distributional changes are predicted to vary depending on species dispersal mode. Here, we address the question of whether clonality is expected to affect the future invasion pattern in PAs.LocationWorldwide.Time period1950–2100.Major taxa studied36 invasive alien plant species.MethodsWe used ensembles of three species distribution models (GLM, GAM and Maxent) based on >70,000 occurrence records to project the distribution of 36 of the world's most invasive clonal and non‐clonal plants in >20,000 PAs. Projections were based on three greenhouse gas concentration scenarios (low, medium and high) for 2080.ResultsClimate change showed little impact on the global invasion pattern in PAs, and clonality showed little effect when all biomes were processed in concert. However, we discerned that the future invasion risk of clonal IAPS markedly increased in biomes located at high elevation and high latitude compared with non‐clonal IAPS, while the risk decreased in lower‐elevation tropical and subtropical biomes where asexual reproduction may be a less successful trait. We also showed that invasion hot spots overlapped with biodiversity hot spots and two realms (i.e. Nearctic and Palearctic), which calls for bridging the gap between invasion and conservation sciences and for more concerted management strategies.Main conclusionsWe suggest that effective management of IAPS in PAs should consider in which biomes PAs are located as well as the reproductive traits of IAPS that are present or may become so.
Maintenance of glycaemic control with liraglutide versus oral antidiabetic drugs as add‐on therapies in patients with type 2 diabetes uncontrolled with metformin alone: A randomized clinical trial in primary care (LIRA‐PRIME)
Authors: Unger Jeff , Allison Dale C. , Kaltoft Margit , Lakkole Kavitha , Panda Jayant K. , Ramesh Chethana , Sargin Mehmet , Smolyarchuk Elena , Twine Melissa , Wolthers Benjamin , Yarimbas Gizem , Zoghbi Marouan ,   the LIRA‐PRIME investigators
Published: October 2021

AbstractAimTo compare (in the LIRA‐PRIME [NCT02730377], a randomized open‐label trial), the efficacy of liraglutide in controlling glycaemia versus an oral antidiabetic drug (OAD) in patients with uncontrolled type 2 diabetes (T2D), despite metformin use in a primary care setting (n = 219 sites, n = 9 countries).Materials and MethodsAdults (n = 1991) with T2D (HbA1c 7.5%‐9.0%) receiving metformin were randomized 1:1 to liraglutide (≤1.8 mg/d) or one OAD, selected by the investigator, added to metformin, for up to 104 weeks. Primary endpoint: time to inadequate glycaemic control (HbA1c > 7.0%) at two scheduled consecutive visits after week 26. Outcomes were assessed for liraglutide versus a pooled OAD group, and (post hoc) liraglutide versus sodium‐glucose co‐transporter‐2 inhibitors, dipeptidyl peptidase‐4 inhibitors, and sulphonylureas individually.ResultsAmong randomized patients (liraglutide, n = 996; OAD, n = 995), 47.6% were female, mean age was 57.4 years and mean HbA1c was 8.2%. Median time to inadequate glycaemic control was 44 weeks longer with liraglutide versus OAD (109 weeks [25% percentile, 38; 75% percentile, not available] vs. 65 weeks [25% percentile, 35; 75% percentile, 107], P < .0001). Changes in HbA1c and body weight at week 104 or at premature treatment discontinuation significantly favoured liraglutide over OAD. Hypoglycaemia rates were comparable between groups and few patients discontinued because of adverse events (liraglutide, 7.9% [n = 79]; OAD, 4.1% [n = 41]). Similar results were observed in the post hoc analysis for liraglutide versus individual OAD classes.ConclusionsGlycaemic control was better maintained with liraglutide versus OAD, supporting liraglutide use when intensifying therapy in primary care patients with T2D.
Weight loss interventions and nonalcoholic fatty liver disease: Optimizing liver outcomes
Authors: Finer Nick 
Published: October 2021

AbstractThe growth in prevalence of obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) has become one of the most important global health challenges. The three chronic diseases are closely linked in their epidemiology and pathophysiology. Currently, weight loss is the most effective treatment for NAFLD (even in the minority of patients with NAFLD who do not have obesity) and is recommended in all national and international guidelines. Accumulating evidence has shown that weight loss, whether achieved by diet and lifestyle interventions, bariatric surgery or pharmacotherapy, can improve biomarkers of NAFLD, as well as prevent progression and, in some cases, reverse fibrosis. There is a dose dependency of weight loss with NAFLD improvement. Pharmacotherapy with antiobesity medications, alone or in combination with intensive lifestyle interventions or other weight‐loss drugs, is closing the efficacy gap between diet and exercise and weight‐loss surgery in efficacy at reversing obesity. Given the importance of providing effective weight‐loss treatment to patients with NAFLD, weight management services need to be made increasingly available and embedded within hepatology services. This narrative review addresses the evidence that weight loss optimizes liver outcomes in people with NAFLD.
Cutaneous adverse reactions after COVID‐19 vaccines in a cohort of 2740 Italian subjects: An observational study
Authors: Grieco Teresa , Maddalena Patrizia , Sernicola Alvise , Muharremi Rovena , Basili Stefania , Alvaro Domenico , Cangemi Roberto , Rossi Alfredo , Pellacani Giovanni 
Published: October 2021

AbstractAn in‐depth characterization of the incidence, morphology, and onset of COVID‐19‐vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID‐19 vaccination‐related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID‐19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine‐related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID‐19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID‐19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID‐19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle.
OV329, a novel highly potent γ‐aminobutyric acid aminotransferase inactivator, induces pronounced anticonvulsant effects in the pentylenetetrazole seizure threshold test and in amygdala‐kindled rats
Authors: Feja Malte , Meller Sebastian , Deking Lillian S. , Kaczmarek Edith , During Matthew J. , Silverman Richard B. , Gernert Manuela 
Published: October 2021

SummaryObjectiveAn attractive target to interfere with epileptic brain hyperexcitability is the enhancement of γ‐aminobutyric acidergic (GABAergic) inhibition by inactivation of the GABA‐metabolizing enzyme GABA aminotransferase (GABA‐AT). GABA‐AT inactivators were designed to control seizures by raising brain GABA levels. OV329, a novel drug candidate for the treatment of epilepsy and addiction, has been shown in vitro to be substantially more potent as a GABA‐AT inactivator than vigabatrin, an antiseizure drug approved as an add‐on therapy for adult patients with refractory complex partial seizures and monotherapy for pediatric patients with infantile spasms. Thus, we hypothesized that OV329 should produce pronounced anticonvulsant effects in two different rat seizure models.MethodsWe therefore examined the effects of OV329 (5, 20, and 40 mg/kg ip) on the seizure threshold of female Wistar Unilever rats, using the timed intravenous pentylenetetrazole (ivPTZ) seizure threshold model as a seizure test particularly sensitive to GABA‐potentiating manipulations, and amygdala‐kindled rats as a model of difficult‐to‐treat temporal lobe epilepsy.ResultsGABA‐AT inactivation by OV329 clearly increased the threshold of both ivPTZ‐induced and amygdala‐kindled seizures. OV329 further showed a 30‐fold greater anticonvulsant potency on ivPTZ‐induced myoclonic jerks and clonic seizures compared to vigabatrin investigated previously. Notably, all rats were responsive to OV329 in both seizure models.SignificanceThese results reveal an anticonvulsant profile of OV329 that appears to be superior in both potency and efficacy to vigabatrin and highlight OV329 as a highly promising candidate for the treatment of seizures and pharmacoresistant epilepsies.
The impact of grade of laryngeal function immediately prior to laryngoplasty and ipsilateral ventriculocordectomy on postoperative performance: 623 Thoroughbred racehorses (1998‐2013)
Authors: Broyles Ali H. , Embertson Rolf M. , Brett Woodie J. , Machado Vinicius 
Published: October 2021

AbstractBackgroundThere is persistent concern among some trainers, owners and veterinarians regarding the effect of preoperative laryngeal function grade on the outcome of laryngoplasty and ventriculocordectomy (LPVC).ObjectivesTo determine the effect of laryngeal function grade prior to LPVC on postoperative performance.Study designRetrospective case‐series.MethodsMedical and race records of Thoroughbred racehorses diagnosed with recurrent laryngeal neuropathy (RLN) and treated with LPVC between 1998 and 2013 were reviewed. Horses were placed into three groups based on preoperative laryngeal function grade (grade III.1, grades III.2/III.3, and grade IV). The effect of preoperative laryngeal function grade on postoperative performance was determined by multivariable logistic regression, Cox proportional hazard model and multivariable linear regression analysis.ResultsIn a multivariable logistic regression, grade III.2/III.3 horses had 1.88 times higher odds (95% CI = 1.03‐3.43) of racing after LPVC than grade IV (P = .04). A multivariable Cox's proportional hazard analysis controlling for race prior to surgery (P < .01) showed that likelihood of racing postoperatively was not different between grade III.1 and grade IV (P = .6), and although not statistically significant, there was a tendency for grades III.2/III.3 to be more likely to race postoperatively than horses with grade IV (P = .07). Kaplan–Meier survival analysis showed that grade IV horses took a longer time to race compared with grade III.1 and grade III.2/III.3. Laryngeal function grade did not influence the mean earnings per start.Main limitationsThe small number of horses in the grade III.1 group compared with the III.2/III.3 and IV groups influenced the effect of grade III.1 on outcome.ConclusionsLaryngeal function grade may affect likelihood of racing after LPVC, but not earnings per start. Grade III. 2/III.3 horses were more likely to race postoperatively than grade IV horses, and grade IV horses took a longer time to first race after LPVC.