bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control
Authors: Hughes Michael S. , Zheng Hui , Zubiri Leyre , Molina Gabriel E. , Chen Steven T. , Mooradian Meghan J. , Allen Ian M. , Reynolds Kerry L. , Dougan Michael 
Published: July 2019

AbstractBackgroundImmune checkpoint inhibitors (CPIs) have revolutionized oncologic therapy but can lead to immune‐related adverse events (irAEs). Corticosteroids are first‐line treatment with escalation to biologic immunosuppression in refractory cases. CPI‐related gastroenterocolitis (GEC) affects 20%‐50% of patients receiving CPIs and can carry significant morbidity and mortality. Severe CPI‐related GEC is not well‐described. We present the clinical characterization of all CPI‐related GEC requiring admission at a single institution.MethodsClinical, laboratory, radiographic, and endoscopic data were extracted from charts of all melanoma patients ≥18 years of age admitted to one institution for CPI‐related GEC, from February 5, 2011 to December 13, 2016. Patients were followed until December 31, 2017 for further admissions. Survival, outcomes, and pharmaceutical‐use analyses were performed.ResultsMedian time‐to‐admission from initial CPI exposure was 73.5 days. Median length of stay was 4.5 days. About 50.0% required second‐line immunosuppression. Readmission for recrudescence occurred in 33.3%. Common Terminology Criteria for Adverse Events (CTCAE) grade was not significantly associated with outcomes. Hypoalbuminemia (P = 0.005), relative lymphopenia (P = 0.027), and decreased lactate dehydrogenase (P = 0.026) were associated with second‐line immunosuppression. There was no difference in progression‐free survival (PFS) or OS (P = 0.367, 0.400) for second‐line immunosuppression. Subgroup analysis showed that early corticosteroid administration (P = 0.045) was associated with decreased PFS.ConclusionsSevere CPI‐related GEC typically manifests within 3 months of immunotherapy exposure. Rates of second‐line immunosuppression and readmission for recrudescence were high. CTCAE grade did not capture the degree of severity in our cohort. Second‐line immunosuppression was not associated with poorer oncologic outcomes; however, early corticosteroid exposure was associated with decreased PFS. Further investigation is warranted.
Tatarinan T, an α‐asarone‐derived lignin, attenuates osteoclastogenesis induced by RANKL via the inhibition of NFATc1/c‐Fos expression
Authors: Zhang Yuxin , Wang Zhi , Xie Xiaona , Wang Shaoming , Wang Yingjian , Quan Guihua , Wang Hongbing , Sun Wan‐chun 
Published: July 2019

AbstractWe have previously reported that the lignin‐like compounds,Tatarinan O(TO) andTatarinan N(TN), extracted from the roots ofAcorus tatarinowii Schott, inhibit receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis. In the present study, the potential function of the α‐asarone‐derived lignins,Tatarinan T(TT) andTatarinan A(TA), to regulate RANKL‐induced osteoclastogenesis was investigated, and it was found that only early treatment with TT may inhibit RANKL‐triggered formation of osteoclasts and resorption. The results revealed repressed expression levels of several osteoclast marker genes, including ATPase H+‐transporting V0 subunit d2 (Atp6v0d2),αvβ3integrin, and osteoclast‐associated receptor (OSCAR), following TT treatment during osteoclastogenesis. Moreover, TT reduced the expression levels of the core transcription elements, nuclear factor of activated T‐cells cytoplasmic 1 (NFATc1) andc‐Fos. However, western blotting analysis showed that TT treatment did not alter nuclear factor‐κΒ (NF‐κB) activation or mitogen‐activated protein kinase (MAPK) or Syk/Btk/phospholipase Cγ2 (PLCγ2) phosphorylation. Taken together, these results suggest the potential of TT in the treatment of diseases of increased bone resorption.
Metal–Helix Frameworks Formed by μ3‐NO3− with Different Orientations and Connected to a Heterometallic CuII10DyIII2 Folded Cluster
Authors: Wang Hai‐Ling , Zhu Zhong‐Hong , Ma Xiong‐Feng , Zou Hua‐Hong , Liang Fu‐Pei 
Published: July 2019

AbstractMetal nanoclusters have a certain rigidity due to their specific coordination patterns and shapes; thus, they face extreme difficulty in folding into a specific direction to form a double‐helix structure and in further interconnecting to form metal–helix frameworks (MHFs). To date, no MHFs have been produced by the formation of heterometallic clusters. Selecting the appropriate “bonding molecules” to bond metal nanoclusters in a specific multiple direction is one of the most effective strategies for designing synthetic MHFs. In this study, we realized for the first time the control of different orientations of μ3‐NO3− to join heterometallic clusters (Cu10Dy2) and subsequently form a left‐handed double helix chain, which further joins to form MHFs. In the structure of the MHFs, four different directions of bridging μ3‐NO3− exist, three of which are involved in the linkage of the double‐helix chain. Each μ3‐NO3− is connected to three adjacent Cu10Dy2. Herein, we extend a new method for designing synthetic double‐helix structures and MHFs, thereby further laying the foundation for the development of similar DNA double‐helix structures and nucleic acid secondary structures in vitro.
Suicides and deaths linked to risky health behavior in childhood cancer patients: A Nordic population‐based register study
Authors: Korhonen Liisa M. , Taskinen Mervi , Rantanen Matti , Erdmann Friederike , Winther Jeanette Falck , Bautz Andrea , Feychting Maria , Mogensen Hanna , Talbäck Mats , Malila Nea , Ryynänen Heidi , Madanat‐Harjuoja Laura 
Published: July 2019

BackgroundChildhood cancer survivors have been reported to be vulnerable to psychiatric morbidities and risky health behavior. Suicides, substance abuse, accidents, and violence as causes of death can be regarded as an extreme manifestation of risky health behavior. In the current study, the authors studied the risk of suicide and other risky health behavior–related deaths among childhood cancer patients in Denmark, Finland, and Sweden.MethodsUsing linkage between national cancer, population, and cause‐of‐death registries, the authors investigated the causes of death in 29,285 patients diagnosed with cancer before age 20 years between 1971 and 2009 compared with a cohort of 146,282 age‐matched, sex‐matched, and country‐matched population comparisons. Rate ratios (RRs) with 95% CIs were estimated using Poisson regression models, adjusting for demographic factors.ResultsThe overall risk of dying of a risky health behavior was found to be increased among childhood cancer patients (RR, 1.25; 95% CI, 1.06‐1.47) when compared with population comparisons. The elevated risk was statistically significant among patients with central nervous system tumors (RR, 1.49; 95% CI, 1.08‐2.05) and patients diagnosed at ages 5 to 9 years and 15 to 19 years (RR, 1.50 [95% CI, 1.01‐2.24] and RR, 1.31 [95% CI, 1.03‐1.67], respectively). The overall risk of suicide was found to be increased (RR, 1.37; 95% CI, 1.02‐1.83), and statistically significantly so when patients were diagnosed between ages 15 and 19 years (RR, 1.61; 95% CI, 1.09‐2.39).ConclusionsChildhood cancer patients appear to have an increased risk of risky health behavior–related causes of death compared with the general population. The results of the current study suggest the importance of integrating psychosocial support into the follow‐up care of these individuals.
Providing health care for patients with childhood cancer and survivors: A survey of pediatric primary care providers
Authors: Wadhwa Aman , Chen Yanjun , Bhatia Smita , Landier Wendy 
Published: July 2019

BackgroundThe current study was conducted to assess self‐reported comfort levels of pediatric primary care providers (PCPs) in providing acute medical care to patients with childhood cancer who currently were receiving therapy (on‐therapy patients) and health maintenance care to childhood cancer survivors, independently and in conjunction with pediatric oncologists, along with confidence levels regarding knowledge about immunizations for survivors. All levels were measured using 7‐point Likert scales.MethodsA cross‐sectional, 23‐item survey mailed to practicing PCPs affiliated with a tertiary children's hospital was analyzed.ResultsThe response rate was 64.4% (259 of 402 eligible PCPs). The mean PCP comfort level was higher when collaborating with a pediatric oncologist to provide acute medical care for on‐therapy patients and health maintenance care for childhood cancer survivors (mean ratings of 6.0 ± 1.5 and 6.4 ± 1.3, respectively) compared with independently providing such care (mean ratings of 4.6 ± 1.8 and 5.0 ± 1.7, respectively; P < .0001). Only approximately 30% of PCPs were confident in their knowledge regarding immunizations for survivors. Certain factors were found to be associated with PCP comfort in providing care in conjunction with a pediatric oncologist. For acute care, these factors were rural location compared with urban location (odds ratio [OR], 5.0; 95% CI, 1.9‐13.1 [P = .03]) and having cared for ≥6 on‐therapy patients within the past year versus none (OR, 3.8; 95% CI, 1.9‐7.5 [P = .0001]). For survivor health maintenance care, practice location <50 miles from pediatric oncology specialty care versus ≥50 miles was the only factor found to be associated with PCP comfort (OR, 2.8; 95% CI, 1.3‐6.1 [P = .009]).ConclusionsThe findings of the current study underscore the need for collaboration between pediatric oncologists and PCPs when caring for children with cancer across the spectrum of care.
Design of efficient fractional operator for ECG signal detection in implantable cardiac pacemaker systems
Authors: Kumar Ashish , Komaragiri Rama , Kumar Manjeet 
Published: July 2019

SummaryA low power and high‐performance digital electrocardiogram (ECG) detector has become a basic requirement in modern implantable cardiac pacemakers. A fractional operator‐based digital ECG detector for modern pacemaker systems is proposed in this work. Instead of conventional thresholding, an adaptive slope prediction threshold is utilized for the detection of ECG peaks. A stochastic search‐based algorithm, namely, cuckoo search algorithm, is used to design an optimal fractional operator that is used for ECG denoising. It has been found that the proposed adaptive slope prediction threshold increases the QRS complex detection performance. A low detection error rate (DER) ranges from 0.01% to 0.56%, positive predictivity (P+) ranges from 99.32% to 99.98%, sensitivity (Se) ranges from 99.45% to 99.98%, and a detection accuracy (Acc) ranges from 99.43% to 99.96% for different databases are achieved for the proposed ECG detector, which is better compared with the existing ECG detectors. The proposed design of fractional order operator based on the lattice wave digital filter (LWDF) requires a minimum number of the multipliers for its structural realization.
Retrospective analysis into differences in heart failure patients with and without iron deficiency or anaemia
Authors: Jacob Christian , Altevers Julia , Barck Isabella , Hardt Thomas , Braun Sebastian , Greiner Wolfgang 
Published: July 2019

AbstractAimsThe aim of this study was to assess the burden of heart failure (HF) patients with/without iron deficiency/iron deficiency anaemia (ID/A) from the health insurance perspective.Methods and resultsWe conducted a retrospective claims database analysis using the Institut für angewandte Gesundheitsforschung Berlin research database. The study period spanned from 1 January 2012 to 31 December 2014. HF patients were identified by International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification codes (I50.‐, I50.0‐, I50.00, I50.01, I50.1‐, I50.11, I50.12, I50.13, I50.14, I50.19, and I50.9). HF patients were stratified into HF patients without ID/A and HF patients with ID/A (D50.‐, D50.0, D50.8, D50.9, and E61.1). HF patients with ID/A were stratified into three subgroups: no iron treatment, oral iron treatment, and intravenous iron treatment. A matching approach was applied to compare outcomes for HF patients without ID/A vs. HF patient with untreated incident ID/A without iron treatment and for HF patients receiving no iron treatment vs. oral iron treatment vs. intravenous iron treatment. Matching parameters included exact age, sex, and New York Heart Association functional class. An optimization algorithm was used to balance total health care costs in the baseline period for the potential matched pairs without sample size reduction. In total, 172 394 (4537.4 per 100 000) HF patients were identified in the Institut für angewandte Gesundheitsforschung Berlin research database in 2013. Of these, 11.1% (19 070; 501.9 per 100 000) were diagnosed with ID/A and/or had a prescription for iron medication in 2013. The mean age of HF patients was 77.0 years (±12.0 years). Women were more frequently diagnosed with HF (54.6%). HF patients with untreated incident ID/A (1.77%) had a significantly higher all‐cause mortality than HF patients without ID/A (33.1% vs. 24.1%, P < 0.01). The analysis of health care utilization revealed significant differences in the rate of all‐cause hospitalization (72.9% vs. 50.5%, P < 0.01). The annual health care costs for HF patients with untreated incident ID/A amounted to €17 347 with incremental costs of €849 (P < 0.01) attributed to ID/A.ConclusionsHeart failure is associated with a major burden for patients and the health care system in terms of health care resource utilization, costs, and mortality. Our findings suggest that there is an unmet need for treating more HF patients with ID/A with iron medication.
Evolution of diet across the animal tree of life
Authors: Román-Palacios Cristian , Scholl Joshua P. , Wiens John J. 
Published: July 2019

AbstractWhat an animal eats is a fundamental aspect of its biology, but the evolution of diet has not been studied across animal phylogeny. Here, we performed a large-scale phylogenetic analysis to address three unresolved questions about the evolution of animal diets. (i) Are diets conserved across animal phylogeny? (ii) Does diet influence rates of species proliferation (diversification) among animal phyla? (iii) What was the ancestral diet of animals and major animal clades? We analyzed diet data for 1087 taxa, proportionally sampled among animal phyla based on the relative species richness of phyla. Our survey suggests that across animals, carnivory is most common (∼63%), herbivory less common (∼32%), and omnivory relatively rare (∼3%). Despite considerable controversy over whether ecological traits are conserved or labile, we found strong conservatism in diet over extraordinarily deep timescales. We found that diet is unrelated to rates of species diversification across animal phyla, contrasting with previous studies showing that herbivory increased diversification within some important groups (e.g., crustaceans, insects, and mammals). Finally, we estimated that the ancestor of all animals was most likely carnivorous, as were many major phyla (e.g., arthropods, molluscs, and chordates). Remarkably, our results suggest that many carnivorous species living today may have maintained this diet through a continuous series of carnivorous ancestors for &gt;800 million years.
From intention to action: A mixed methods study of clients’ experiences of goal‐oriented practices
Authors: Di Malta Gina , Oddli Hanne W. , Cooper Mick 
Published: July 2019

AbstractObjectivesGoal‐oriented practices are central to many contemporary psychotherapies. The aim of this study was to explore clients’ experiences of this work.DesignMixed methods, with a main qualitative part and a smaller quantitative component. Participants were 22 clients in integrative psychotherapy (15 females, 6 males, 1 other). Semi‐structured interviews after session 4 and at endpoint were analyzed thematically. On the basis of the identified themes, “goal attitude” scores were developed and their correlations with outcomes investigated.ResultsGoal‐oriented practices could help clients move from intention to action through increased awareness and focus, setting manageable tasks, and progress monitoring. However, they had the potential to hinder clients’ awareness of their intentions, feel irrelevant, disorientating, or demotivating. Effectiveness hinged on client's management of their expectations, flexible working, and time. Positive attitudes toward goal‐oriented practices were associated with improvement.ConclusionsGoal‐oriented practices can enhance psychotherapeutic work but need to be individually tailored and implemented collaboratively.
Retracted: MicroRNA‐204‐3p represses colon cancer cells proliferation, migration, and invasion by targeting HMGA2
Authors: Xi Xiangpeng , Teng Mujian , Zhang Liang , Xia Lijian , Chen Jingbo , Cui Zhonghui 
Published: July 2019

AbstractColon cancer is a detrimental neoplasm of the digestive tract. MicroRNAs (miRNAs) as central regulators have been discovered in colon cancer. Nonetheless, the impact of miR‐204‐3p on colon cancer remains indistinct. The research attempted to uncover the impacts of miR‐204‐3p on colon cancer cells growth, migration, and invasion. miR‐204‐3p expression level in colon cancer tissues and diverse colon cancer cell lines were testified by the quantitative real‐time polymerase chain reaction. Exploration of the impacts of miR‐204‐3p on cell growth, migration, invasion, and their associated factors through assessment of CCK‐8, flow cytometry, Transwell, and western blot, respectively. High mobility group AT‐hook 2 (HMGA2) expression was then detected in Caco‐2 cells after miR‐204‐3p mimic and inhibitor transfection, additionally dual‐luciferase activity was implemented to further uncover the correlation between HMGA2 and miR‐204‐3p. The impact of HMGA2 on Caco‐2 cell growth, migration, and invasion was finally assessed. We found that repression of miR‐204‐3p was discovered in colon cancer tissues and HCT116, SW480, Caco‐2, HT29 and SW620 cell lines. MiR‐204‐3p overexpression mitigated Coca‐2 cell viability, facilitated apoptosis, simultaneously adjusted CyclinD1 and cleaved caspase‐3 expression. Cell migration, invasion, and the associated factors were all suppressed by miR‐204‐3p overexpression. Reduction of HMGA2 was presented in Caco‐2 cells with miR‐204‐3p mimic transfection, and HMGA2 was predicated to be a target gene of miR‐204‐3p. Besides, HMGA2 silence showed the inhibitory effect on Caco‐2 cells growth, migration, and invasion. In conclusion, miR‐204‐3p repressed colon cancer cell growth, migration, and invasion through targeting HMGA2.
Population Pharmacokinetic Modeling of Gentamicin in Pediatrics
Authors: Wang Hechuan , Sherwin Catherine , Gobburu Jogarao V.S. , Ivaturi Vijay 
Published: July 2019

AbstractThe primary objective of this work was to characterize the pharmacokinetics (PK) of gentamicin across the whole pediatric age spectrum from premature neonates to young adults with a single model by identifying significant clinical predictors. A nonlinear mixed‐effect population PK model was developed with retrospective therapeutic drug‐monitoring data. A total of 6459 drug concentration measurements from 3370 hospitalized patients were collected for model building (n = 2357) and evaluation (n = 1013). In agreement with previously reported models, a 2‐compartment model with first‐order elimination best described the drug PK. Patient‐specific factors significantly impacting gentamicin clearance included fat‐free mass, postmenstrual age, and serum creatinine (SCr). Based on our model, the deviation of the individual SCr from the age‐dependent expected mean SCr value (SCrM) can result in a 40% lower clearance in a patient with renal impairment than that in a patient with normal kidney function, with SCrM:SCr ratios between 0.16 and 3.2 in this study. Consistent with the known age‐dependent changes of the proportion of extracellular water in body weight, the inclusion of the impact of extracellular water maturation on the central volume of distribution was found to improve the model fitting significantly. In comparison with other published models, model evaluation suggested the developed model was the least biased and physiologically most representative. These results will be used to inform individualized initial dosing strategies and serve as a prior PK model for Bayesian updating and forecasting as individual clinical observations become available.
Effect of zinc‐biofortified seeds on grain yield of wheat, rice, and common bean grown in six countries
Authors: Rashid Abdul , Ram Hari , Zou Chun-Qin , Rerkasem Benjavan , Duarte Aildson P. , Simunji Simunji , Yazici Atilla , Guo Shiwei , Rizwan Muhammad , Bal Rajinder S. , Wang Zhaohui , Malik Sudeep S. , Phattarakul Nattinee , Soares de Freitas Rogerio , Lungu Obed , Barros Vera L. N. P. , Cakmak Ismail 
Published: July 2019

AbstractSeeds enriched with zinc (Zn) are ususally associated with better germination, more vigorous seedlings and higher yields. However, agronomic benefits of high‐Zn seeds were not studied under diverse agro‐climatic field conditions. This study investigated effects of low‐Zn and high‐Zn seeds (biofortified by foliar Zn fertilization of maternal plants under field conditions) of wheat (Tritcum aestivum L.), rice (Oryza sativa L.), and common bean (Phaseolus vulgaris L.) on seedling density, grain yield and grain Zn concentration in 31 field locations over two years in six countries. Experimental treatments were: (1) low‐Zn seeds and no soil Zn fertilization (control treatment), (2) low‐Zn seeds + soil Zn fertilization, and (3) Zn‐biofortified seeds and no soil Zn fertilization. The wheat experiments were established in China, India, Pakistan, and Zambia, the rice experiments in China, India and Thailand, and the common bean experiment in Brazil. When compared to the control treatment, soil Zn fertilization increased wheat grain yield in all six locations in India, two locations in Pakistan and one location in China. Zinc‐biofortified seeds also increased wheat grain yield in all four locations in Pakistan and four locations in India compared to the control treatment. Across all countries over 2 years, Zn‐biofortified wheat seeds increased plant population by 26.8% and grain yield by 5.37%. In rice, soil Zn fertilization increased paddy yield in all four locations in India and one location in Thailand. Across all countries, paddy yield increase was 8.2% by soil Zn fertilization and 5.3% by Zn‐biofortified seeds when compared to the control treatment. In common bean, soil Zn application as well as Zn‐biofortified seed increased grain yield in one location in Brazil. Effects of soil Zn fertilization and high‐Zn seed on grain Zn density were generally low. This study, at 31 field locations in six countries over two years, revealed that the seeds biofortfied with Zn enhanced crop productivity at many locations with different soil and environmental conditions. As high‐Zn grains are a by‐product of Zn biofortification, use of Zn‐enriched grains as seed in the next cropping season can contribute to enhance crop productivity in a cost‐effective manner.