bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects and safety of PD‐1/PD‐L1 inhibitors on head and neck cancer: A systematic review and meta‐analysis
Authors: Wang Bi‐Cheng , Cao Ru‐Bo , Li Pin‐Dong , Fu Chen
Published: August 2019

Background

Inhibitors of programmed cell death‐1 (PD‐1) and its ligand (PD‐L1) have been increasingly used in head and neck cancer therapy and reported to improve the outcomes with an acceptable safety profile. This systematic review and meta‐analysis was conducted to assess the benefit and risk of PD‐1/PD‐L1 inhibitors in patients with head and neck cancer.

Method

The PubMed, Cochrane Library, EMBASE and Web of Science databases were systematically searched to find potentially eligible studies up to May 30, 2019. Primary outcomes were overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events.

Results

Overall, this analysis consisted of nine eligible studies, with two randomized controlled trials and seven single arm trials. In the treatment of recurrent or metastatic head and neck cancer, PD‐1 inhibitors showed significantly lower relative risk of death than standard‐of‐care therapy (odds ratio [OR] = 0.60, 95% confidence interval [CI]: 0.44‐0.82, I2 = 0%, P = .001). Programmed cell death‐1 inhibitors also decreased the risk of disease progression, however, there was no statistically significant difference of PFS between the treatments (OR = 0.69, 95% CI: 0.48‐1.01, I2 = 0%, P = .05). Subgroup analysis showed that human papillomavirus (HPV) positive patients had higher response rates than HPV negative patients in PD‐1/PD‐L1 inhibitors‐treated population (ORR: 18.8% vs 12.2%; DCR: 42.8% vs 34.4%). The most common any‐grade and grade ≥3 treatment‐related adverse events were fatigue (14.7%, 95% CI: 12.3%‐17.1%) and aspartate aminotransferase increased (1.6%, 95% CI: 0.3%‐2.9%), respectively.

Conclusion

Programmed cell death‐1 inhibitors prolonged OS in comparison with standard‐of‐care therapy in recurrent or metastatic head and neck cancer patients. Human papillomavirus positive patients were superior to HPV negative patients in the treatment of PD‐1/PD‐L1 inhibitors. More phase III randomized controlled trials are warranted to confirm our findings.
Absolute configuration of phomactatriene diterpenoids obtained by Wagner‐Meerwein rearrangement of epimeric verticillols
Authors: del Río‐Chávez Ángel A. , García‐Gutiérrez Hugo A. , Román‐Marín Luisa U. , Beiza‐Granados Lidia , Cerda‐García‐Rojas Carlos M. , Joseph‐Nathan Pedro , Hernández‐Hernández Juan D.
Published: August 2019

The epimeric diterpenes (+)‐(1S,3E,7E,11S,12S)‐verticilla‐3,7‐dien‐12‐ol (1), isolated from Bursera suntui, and (+)‐(1S,3E,7E,11S,12R)‐verticilla‐3,7‐dien‐12‐ol (2), isolated from Bursera kerberi, gave the same Wagner‐Meerwein rearrangement product (−)‐(1E,4Z,8Z,11S,12R)‐phomacta‐1,(15)4,8‐triene (3). The Et2O:BF3‐induced transformations evidence that verticillenes and phomactanes, both containing the bicyclo[9.3.1]pentadecane skeleton, are biogenetically related through the verticillen‐12‐yl cation (A+), which also is a key intermediate in the biosynthetic pathways to generate antitumor taxanes. Molecular modeling using the Monte Carlo protocol, followed by density functional theory (DFT) geometry optimization employing the hybrid functionals B3LYP and B3PW91, both with the DGDZVP basis set, secured the configuration of 3 as followed from the good agreement between the calculated and experimental vibrational circular dichroism spectra. Similar DFT calculations allowed determining the absolute configuration of (+)‐(1R,4R,5R,8S,9S,11S,12R,15R)‐1,15:4,5:8,9‐triepoxyphomactane (9), which surprisingly derives from epoxidation of the second minimum energy conformer of 3.
Enantioseparation and determination of flumequine enantiomers in multiple food matrices with chiral liquid chromatography coupled with tandem mass spectrometry
Authors: Li Shuang , Liu Beibei , Xue Mengyao , Yu Jia , Guo Xingjie
Published: August 2019

The present work firstly described the enantioseparation and determination of flumequine enantiomers in milk, yogurt, chicken, beef, egg, and honey samples by chiral liquid chromatography‐tandem mass spectrometry. The enantioseparation was performed under reversed‐phase conditions on a Chiralpak IC column at 20°C. The effects of chiral stationary phase, mobile phase components, and column temperature on the separation of flumequine enantiomers have been studied in detail. Target compounds were extracted from six different matrices with individual extraction procedure followed by cleanup using Cleanert C18 solid phase extraction cartridge. Good linearity (R2>0.9913) was obtained over the concentration range of 0.125 to 12.5 ng g‐1 for each enantiomer in matrix‐matched standard calibration curves. The limits of detection and limits of quantification of two flumequine enantiomers were 0.015‐0.024 and 0.045‐0.063 ng g‐1, respectively. The average recoveries of the targeted compounds varied from 82.3 to 110.5%, with relative standard deviation less than 11.7%. The method was successfully applied to the determination of flumequine enantiomers in multiple food matrices, providing a reliable method for evaluating the potential risk in animal productions.
Synthesis of alternating metallocopolymers by chiral recognition
Authors: Torres‐Werlé Maria , Heinrich Benoît , Maisse‐François Aline , Bellemin‐Laponnaz Stéphane
Published: August 2019

We report the synthesis of chiral enantiopure polytopic bridging ligands, which may lead to the formation of metallosupramolecular polymers with zinc (II) as metal linker. We show that chiral C2‐symmetric bisoxazoline ligands are useful moieties to efficiently generate heterochiral complexes and thus polymeric entities. The corresponding metallopolymers were further characterized by powder X‐ray diffraction (PXRD) to obtain information on the level of crystallinity of our different metallopolymers.
On the Ethereum blockchain structure: A complex networks theory perspective
Authors: Ferretti Stefano , D'Angelo Gabriele
Published: August 2019

In this paper, we analyze the Ethereum blockchain using the complex networks modeling framework. Accounts acting on the blockchain are represented as nodes, while the interactions among these accounts, recorded on the blockchain, are treated as links in the network. Using this representation, it is possible to derive interesting mathematical characteristics that improve the understanding of the actual interactions happening in the blockchain. Not only, by looking at the history of the blockchain, it is possible to verify if radical changes in the blockchain evolution happened.
Silicon Nanoparticles Embedded in N‐Doped Few‐Layered Graphene: Facile Synthesis and Application as an Effective Anode for Lithium Ion Batteries
Authors: Luan Yuting , Yang Bowen , Zhu Kai , Shao Shuangxi , Gao Yinyi , Cheng Kui , Yan Jun , Ye Ke , Wang Guiling , Cao Dianxue
Published: August 2019

A fast one‐step arc discharge exfoliation method is employed to synthesize Si/graphene composites by using a graphite rod filled with a mixture of Si powder and urea as a cathode. During the arc discharge process, the use of urea allows both the introduction of nitrogen atoms into the graphene and the uniform sealing of Si nanoparticles between the thin graphene sheets to occur simultaneously. The resulting N‐doped graphene nanosheets embedded with Si (Si@NG) can act as an electrode material for lithium‐ion batteries and delivers the reversible capacity of 1030 mAh g−1 with a current density of 200 mA g−1 over 100 cycles along with an outstanding coulombic efficiency of 96.84 %. The remarkable electrochemical rate capability performance can be owed to the multiple role of NG, which not only serves as a three‐dimensional conductive support, but also effectively limits the volume variation of Si nanoparticles. The approach proposed here is expected to be extended to the preparation of other alloy anode/graphene hybrids for lithium ion batteries.
2 D Materials for Inhibiting the Shuttle Effect in Advanced Lithium–Sulfur Batteries
Authors: Ali Tariq , Yan Chenglin
Published: August 2019

A lithium–sulfur battery is a new energy storage device with low cost, high energy storage density, and environmental protection. It is an important tool for future battery systems. However, owing to the shuttle of polysulfides, insulation performance of sulfur, and volume change, capacity decay and cycle instability result, which limits the future application of lithium–sulfur batteries. 2 D materials, such as graphene, carbide, nitride, sulfide, oxide, and their aggregates, provide high surface area to improve sulfur utilization and cycle performance. In this Minireview, various 2 D materials are summarized that use physical confinement and chemical interactions to inhibit the shuttle of polysulfides. We outline the controlled spacing of 2 D materials, abundant active sites, and large transverse size separators and interlayers. The effects on the interlayer and separator based on 2 D materials at the lithium anode prevent polysulfide dissolution are also reviewed. Finally, the challenges and prospects of 2 D materials for lithium–sulfur batteries are discussed.
GUIDE: Smartphone sensors‐based pedestrian indoor localization with heterogeneous devices
Authors: Ashraf Imran , Hur Soojung , Shafiq Muhammad , Kumari Saru , Park Yongwan
Published: August 2019

A plethora of indoor localization systems based on Wi‐Fi, radio frequency chips, ultra‐wide‐band, and bluetooth have been proposed, yet these systems do not work when the infrastructure is absent. On the other hand, infrastructure less systems benefit mostly from off‐the‐shelf smartphone sensors and do not need additional hardware. This study shows a similar indoor localization approach which turns smartphone built‐in sensors to good account. We take advantage of magnetic field strength fingerprinting approach to localize a pedestrian indoor. In addition, accelerometer and gyroscope sensors are utilized to find the pedestrian's traveled distance and heading estimation, respectively. Our aim is to solve the problem of device dependence by devising an approach that can perform localization using various smartphones in a similar fashion. We make the use of patterns of magnetic field strength to formulate the fingerprint database to achieve this goal. This approach solves two problems: need to update the database periodically and device dependence. We conduct experiments using Samsung Galaxy S8 and LG G6 for five different buildings with different dimensions in Yeungnam University, Republic of Korea. The evaluation is performed by following three different path geometries inside the buildings. The results show that the proposed localization approach can potentially be used for indoor localization with heterogeneous devices. The errors for path 1 and path 2 are very similar, however, localization error for path 3 is comparatively higher because of the complexity of the path 3. The mean and median errors for Galaxy S8 are 1.37 and 0.88 m while for LG G6, these are 1.84 and 1.21 m, respectively, while considering all buildings and all paths followed during the experiment. Overall, the proposed approach can potentially localize a pedestrian within 1.21 m at 50% and within 1.93 m at 75%, irrespective of the device used for localization. The performance of the proposed approach is compared with the K nearest neighbor (KNN) for evaluation. The proposed approach outperforms the KNN
Optimal location management in LTE networks using evolutionary techniques
Authors: Aqeeli Emad , Hashim Hashim A. , Haque Anwar , Shami Abdallah
Published: August 2019

Wireless network is considered a vital enabler in the world of information technology, specifically, LTE and LTE advanced networks, which are the latest technologies owing to their fast speed, robustness, and large bandwidth. However, in spite of the aforementioned advancements, signaling overhead poses critical challenges in terms of network availability, especially those caused by location management messages which are related to users’ mobility behavior. This paper seeks to address the problem of signaling overhead caused by the location management messages specifically, tracking area update (TAU) and paging by deploying three evolutionary algorithms, namely particle swarm optimization (PSO), artificial bee colony (ABC), and gravitational search algorithm (GSA). The deployed algorithms guarantee yielding the minimum values of the signaling overhead for TAU, paging, and the battery power consumption of the user. It is shown that ABC‐based algorithm has faster convergence and better signaling overhead when compared with other implemented algorithms. Moreover, the measured relative standard deviation (RSD) value of all algorithms shows low uncertainty of around 1% for the objective function and 3% for the paging, TAU, and power. Hence, the three applied optimization algorithms have proven to be efficient and reliable for solving the problem in a large‐scale environment.
Consider the intellectual property aspects of technology transfers in the higher ed world
Authors: Reed Julie L. , Wagner Justin D.
Published: August 2019

Many scenarios exist for technology transfer in commercializing intellectual property in the university environment. Sponsoring organizations may pay to fund research and then use any rights they have in their own company, or use them to found a subsidiary. Government‐funded research may be transferred to a government lab or agency. The university itself may decide to “spin out” technology developed by a faculty member within the university. This generally means the university will assist in the founding of a startup company to commercialize the research. This last scenario is of particular interest here, and the discussion that follows focuses on the intellectual property considerations in such a transfer, rather than the structure of the company itself.
Get ready to respond to requests from students with disabilities
Authors: Charmatz Marc
Published: August 2019

A new school year is about to begin, and you and your colleagues are no doubt busy getting ready for students with disabilities — new first‐year students and transfer students who may be making requests for auxiliary aids and services and reasonable modifications of school policies and procedures. Here are some hopefully helpful hints in processing student requests.
Disability representation creates cultural change on college campuses
Authors: LoGiudice Joseph A.
Published: August 2019

On Sunday, June 9, 2019, Ali Stroker, who uses a wheelchair, won the Tony Award for best supporting actress in a musical for her role as Ado Annie in Oklahoma! She is the first person who uses a wheelchair to be nominated and win this prestigious award. But why should disability services professionals care about this historic moment?
Matrotrophic viviparity constrains microbiome acquisition during gestation in a live‐bearing cockroach, Diploptera punctata
Authors: Jennings Emily C. , Korthauer Matthew W. , Hamilton Trinity L. , Benoit Joshua B.
Published: August 2019

The vertical transmission of microbes from mother to offspring is critical to the survival, development, and health of animals. Invertebrate systems offer unique opportunities to conduct studies on microbiome‐development‐reproduction dynamics since reproductive modes ranging from oviparity to multiple types of viviparity are found in these animals. One such invertebrate is the live‐bearing cockroach, Diploptera punctata. Females carry embryos in their brood sac, which acts as the functional equivalent of the uterus and placenta. In our study, 16S rRNA sequencing was used to characterize maternal and embryonic microbiomes as well as the development of the whole‐body microbiome across nymphal development. We identified 50 phyla and 121 classes overall and found that mothers and their developing embryos had significantly different microbial communities. Of particular interest is the notable lack of diversity in the embryonic microbiome, which is comprised exclusively of Blattabacteria, indicating microbial transmission of only this symbiont during gestation. Our analysis of postnatal development reveals that significant amounts of non‐Blattabacteria species are not able to colonize newborn D. punctata until melanization, after which the microbial community rapidly and dynamically diversifies. While the role of these microbes during development has not been characterized, Blattabacteria must serve a critical role providing specific micronutrients lacking in milk secretions to the embryos during gestation. This research provides insight into the microbiome development, specifically with relation to viviparity, provisioning of milk‐like secretions, and mother–offspring interactions during pregnancy.
Development of high‐resolution DNA barcodes for Dioscorea species discrimination and phylogenetic analysis
Authors: Xia Wei , Zhang Bo , Xing Dan , Li Ying , Wu Wenqiang , Xiao Yong , Sun Jinhua , Dou Yajing , Tang Wenqi , Zhang Jinlan , Huang Xiaolong , Xu Yun , Xie Jun , Wang Jihua , Huang Dongyi
Published: August 2019

The genus Dioscorea is widely distributed in tropical and subtropical regions, and is economically important in terms of food supply and pharmaceutical applications. However, DNA barcodes are relatively unsuccessful in discriminating between Dioscorea species, with the highest discrimination rate (23.26%) derived from matK sequences. In this study, we compared genic and intergenic regions of three Dioscorea chloroplast genomes and found that the density of SNPs and indels in intergenic sites was about twice and seven times higher than that of SNPs and indels in the genic regions, respectively. A total of 52 primer pairs covering highly variable regions were designed and seven pairs of primers had 80%–100% PCR success rate. PCR amplicons of 73 Dioscorea individuals and assembled sequences of 47 Dioscorea SRAs were used for estimating intraspecific and interspecific divergence for the seven loci: The rpoB‐trnC locus had the highest interspecific divergence. Automatic barcoding gap discovery (ABGD), Poisson tree processes (PTP), and generalized mixed Yule coalescence (GMYC) analysis were applied for species delimitation based on the seven loci and successfully identified the majority of species, except for species in the Enantiophyllum section. Phylogenetic analysis of 51 Dioscorea individuals (28 species) showed that most individuals belonging to the same species tended to cluster in the same group. Our results suggest that the variable loci derived from comparative analysis of plastid genome sequences could be good DNA barcode candidates for taxonomic analysis and species delimitation.
Spatial variability of mangrove primary productivity in the neotropics
Authors: Ribeiro Rafaela de Albuquerque , Rovai André Scarlate , Twilley Robert R. , Castañeda‐Moya Edward
Published: August 2019

Mangroves are considered one of the most productive ecosystems in the world with significant contributions as carbon sinks in the biosphere. Yet few attempts have been made to assess global patterns in mangrove net primary productivity, except for a few assumptions relating litterfall rates to variation in latitude. We combined geophysical and climatic variables to predict mangrove litterfall rates at continental scale. On a per‐area basis, carbon flux in litterfall in the neotropics is estimated at 5 MgC·ha−1·yr−1, between 20% and 50% higher than previous estimates. Annual carbon fixed in mangrove litterfall in the neotropics is estimated at 11.5 TgC, which suggests that current global litterfall estimates extrapolated from mean reference values may have been underestimated by at least 5%. About 5.8 TgC of this total carbon fixed in the neotropics is exported to estuaries and coastal oceans, which is nearly 30% of global carbon export by tides. We provide the first attempt to quantify and map the spatial variability of carbon fixed in litterfall in mangrove forests at continental scale in response to geophysical and climatic environmental drivers. Our results strengthen the global carbon budget for coastal wetlands, providing blue carbon scientists and coastal policy makers with a more accurate representation of the potential of mangroves to offset carbon dioxide emissions.
Geese mediate vegetation state changes with parallel effects on N cycling that leave nutritional legacies for offspring
Authors: Ruess R. W. , McFarland J. W. , Person B. , Sedinger J. S.
Published: August 2019

Along the coastal fringe of the Yukon–Kuskokwim River Delta in southwestern Alaska, geese maintain grazing lawns dominated by a rhizomatous sedge that, when ungrazed, transitions to a taller, less palatable growth form that is taxonomically described as a different species. Nutrients recycled in goose feces, in conjunction with grazing, are critical to the rapid, nutritious growth of grazing lawns, and selective foraging on lawns has positive life‐history consequences for goslings. To examine whether bidirectional vegetation shifts were accompanied by parallel changes in N cycling, we studied how 15N‐urea and 13C15N‐glycine were processed through soils and plants of native and recently reverted vegetation states. Biomass and plant 15N uptake from plots reverted to the tall growth form using exclosures and from those shifted to grazing lawns by experimental clipping and then goose grazing were identical to their native counterparts. Total recovery of 15N within the tall vegetation types was significantly greater than within grazing lawns, although when expressed on a per‐gram biomass basis, percentage of 15N recovery was significantly higher in grazing lawns compared with the tall vegetation state. Patterns of 13C enrichment in CO2 soil efflux showed rapid use of 13C‐glycine as a respiratory substrate within the first hour following injection, with both the timing and magnitude of efflux occurring at similar time points for all four vegetation types. However, higher soil respiration rates and a shorter half‐life for 13C‐glycine in soils from tall meadows resulted in a greater proportional loss of 13CO2 compared with grazing lawns. Despite daily‐to‐weekly tidal inundation, all of 15N from labeled substrates could be accounted for within 1 m of the injection grid from soils of both states after 30 d, with significant levels of 15N in soils and vegetation after one year. Geese have remarkably high fidelity to brood‐rearing areas, returning as adults to the same grazing lawns where they were raised as goslings. Our data suggest that the role fecal‐derived nutrients play in the positive feedback loop between geese and their food resources can provide a long‐term legacy that spans generations.
Hepatic steatosis in patients with acromegaly
Authors: Koutsou‐Tassopoulou Andreani , Papapostoli‐Sklavounou Ifigeneia , Krawczyk Marcin , Friesenhahn‐Ochs Bettina , Weber Susanne N. , Lammert Frank , Stokes Caroline S.
Published: August 2019

Objective

Comorbid NAFLD is increasingly being diagnosed in patients with diabetes and nondiabetic endocrinopathies. The aim of this study was to assess hepatic steatosis noninvasively by transient elastography in patients with acromegaly.

Design

A cross‐sectional study including 22 patients with acromegaly.

Methods

Hepatic steatosis was quantified using controlled attenuation parameter (CAP) during elastography. Anthropometric measurements were obtained, serum liver function tests and lipid and hormone profiles were measured, and prosteatogenic gene variants were genotyped using standard assays.

Results

In total, 41% of patients were women (mean age 60 ± 14.7 years, mean BMI 31.2 ± 4.6 kg/m2). Hepatic steatosis, as defined by CAP > 248 dB/m, was present in 66% of patients. Five (45%) of the patients with hepatic steatosis also had fibrosis, and one presented with cirrhosis. Nine patients were carriers of the PNPLA3 p.I148M prosteatogenic [M] risk allele, eight of whom were heterozygotes. CAP values were significantly (P = .045) higher in these patients and corresponded to advanced steatosis, as compared to patients with the wild‐type genotype, who demonstrated CAP values consistent with mild steatosis (311 ± 33 dB/m. vs 254 ± 62 dB/m). CAP values did not differ significantly in carriers of distinct TM6SF2 and MBOAT7 genotypes; however, carriers of the risk alleles displayed higher CAP as compared to wild‐type patients.

Conclusions

This study shows that in patients with acromegaly, carriers of the PNPLA3 susceptibility allele are at risk of developing hepatic steatosis, as assessed by CAP. Comorbid NAFLD might compound prognosis in such patients; thus, further research into the pathomechanisms and treatment of NAFLD in acromegaly is warranted.
Identification of fungi associated with soybeans and effective seed disinfection treatments
Authors: Escamilla Diana , Rosso Maria Luciana , Zhang Bo
Published: August 2019

Sprouts can be a vehicle for the transmission of several pathogens capable of causing human illness, and the potential source of contamination is seed used for sprouting. The limited information about seed‐borne pathogens as well as their incidence on soybean seeds for soybean sprout industry led the objectives of this study that were to identify seed‐borne pathogens on commercial sprout soybean seeds and to evaluate different decontamination treatments on disinfection effectiveness and sprout quality. Seeds of “MFS‐561,” a sprout soybean cultivar, from three production regions were used in this study. The internal transcribed spacer (ITS1 and ITS2) DNA sequences of the isolated fungi from MFS‐561 seeds were used for species identification. Seven disinfection treatments were evaluated on their effectiveness on reducing fungal incidence and impact on sprout characteristics. Out of 55 fungal isolates obtained from the soybean seeds, seven species and six genera were identified. The most frequent genera across regions were Alternaria, Diaphorte, and Fusarium. The treatment of soaking seeds in 2% calcium hypochlorite for 10 min and 5% acetic acid for 2 min before sprouting were promising seed disinfection treatments as they significantly reduced fungi incidence without any negative effects on sprout quality.
Impact of type 2 diabetes mellitus and physical activity on medication costs in older adults
Authors: Kikuti‐Koyama Kelly Akemi , Monteiro Henrique Luiz , Ribeiro Lemes Ítalo , de Morais Luana Carolina , Fernandes Rômulo , Turi‐Lynch Bruna , Codogno Jamile
Published: August 2019

Introduction

The high prevalence of diabetes mellitus leads to high costs of medication for treatment and the practice of physical activity, as well as reducing the risks of diabetes mellitus is able to substantially mitigate costs. To investigate the impact of diabetes mellitus on costs of medication and identify whether physical activity can influence the relationship between diabetes mellitus and costs of medication.

Methods

The sample consisted of adults enrolled in five basic healthcare units. The presence of diabetes mellitus and habitual physical activity were assessed by a questionnaire, the quantity of medication used was evaluated according to the medical records, and medication costs, through receipts.

Findings

Individuals with diabetes mellitus from baseline presented higher body weight (P value = .001) and lower levels of physical activity (P value = .014). The presence of diabetes mellitus was positively related to costs of medication for diseases of the circulatory system (β = 4.89), endocrine, nutritional, and metabolic diseases (β = 109.72), and total costs of medication (β = 113.41). The impact of diabetes mellitus was attenuated by physical activity.

Conclusion

It was identified that diabetes mellitus has a significant impact on public costs with medication, and physical activity was effective in reducing health costs independently of diabetes mellitus by less than 1%.
Lots of little ones: Analysis of charitable donations to a hospice and palliative care unit in Taiwan
Authors: Hsu Ya‐Chuan , Chu Feng‐Yuan , Chen Tzeng‐Ji , Chou Li‐Fang , Chang Hsiao‐Ting , Lin Ming‐Hwai , Hwang Shinn‐Jang
Published: August 2019

Background

Charitable donations play a major role in the provision of hospice and palliative care (HPC) services, most of which are not reimbursed by health insurance programs. A good understanding of the constitution and use of donations is thus conducive to maintaining a high‐quality HPC unit.

Methods

The data sources were the publicly available balance sheet, work report, and donor lists of a foundation exclusively supporting one of the best HPC units in Taiwan in the fiscal year of 2017. The analysis included the donation amounts and frequencies by donor type (individual, corporate, and group) and the categories of expenses.

Results

The foundation received 3033 donations worth a total of 7.8 million New Taiwan dollars (NTD) (approximately 258 thousand US dollars) in 2017. Two‐thirds of the donations were allocated to the provision of direct care services. Of the 3033 donations, only 11 (0.4%) were worth 100 000 NTD or more, while 108 (3.6%) were valued between 10 000 and 99 999 NTD, 1268 (41.8%) were valued between 1000 and 9999 NTD, and 1646 (54.2%) were worth less than 1000 NTD. Of 1051 donors, 974 (92.7%) were individuals, 378 (36.0%) donated more than once, and 106 (10.1%) donated 12 or more times in one year.

Conclusion

HPC services in Taiwan are sponsored by lots of individuals and small donations. For sustainability of standards‐based and quality HPC services, the benevolence of the public should be thus cherished and adequately responded to.
miR‐496 remedies hypoxia reoxygenation–induced H9c2 cardiomyocyte apoptosis via Hook3‐targeted PI3k/Akt/mTOR signaling pathway activation
Authors: Jin Yongping , Ni Shimao
Published: August 2019

The hypoxia‐reoxygenation (H/R) model helps analyze myocardial infarction triggered by acute myocardial ischemia, which induces cardiomyocyte proliferation and apoptosis. The Gene Expression Omnibus database was used to obtain the GSE74205 and GSE3866 microarray data, including microRNA (miRNA) and messenger RNA profiles, to catalog potential key miRNAs and genes. The role of rno‐mir‐496 expression in cardiomyocyte proliferation within 10 days of birth was established. The microRNA Target Prediction Database (miRDB) database—via Gene Ontology annotation—predicted hook microtubule tethering protein 3 (Hook3), a key target gene of rno‐mir‐496, was closely related to cell proliferation. Upregulation of miR‐496 related to a significant reduction in apoptosis of H9c2 and human cardiomyocytes treatment with H/R. Moreover, transfection of H9c2 cells with miR‐496 mimics, which were pretreated with H/R for 12 hours, increased Ki67 levels, proliferating cell nuclear antigen and Bcl‐2 proteins; and decreased cleaved caspase‐3 and Bax protein levels, as determined by reverse transcription‐polymerase chain reaction and Western blot assays. A dual‐luciferase reporter system confirmed that miR‐496 targets the Hook3 suppressor. Hook3 overexpression stimulated apoptosis in H/R‐treated cells, thus reducing cell proliferation. Upregulated miR‐496 activated phosphatidylinositol‐3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling, while Hook3 exhibited the inverse trend in H/R‐treated H9c2 cells. In summary, with Hook3 functionality's aid, miR‐496 upregulation defends cells from H/R‐induced apoptosis and stimulates cell proliferation. miR‐496 targets Hook3 to trigger the PI3K/Akt/mTOR signaling pathway for antiapoptotic and proliferative effects.
Metastasis and cachexia: alongside in clinics, but not so in animal models
Authors: Tomasin Rebeka , Martin Ana Carolina Baptista Moreno , Cominetti Márcia Regina
Published: August 2019

Cancer cachexia is a paraneoplastic syndrome characterized by lean mass wasting (with or without fat mass decrease), culminating in involuntary weight loss, which is the key clinical observation nowadays. There is a notable lack of studies involving animal models to mimic the clinical reality, which are mostly patients with cachexia and metastatic disease. This mismatch between the clinical reality and animal models could at least partly contribute to the poor translation observed in the field. In this paper, we retrieved and compared animal models used for cachexia research from 2017 and 10 years earlier (2007) and observed that very little has changed. Especially, clinically relevant models where cachexia is studied in an orthotopic or metastatic context were and still are very scarce. Finally, we described and supported the biological rationale behind why, despite technical challenges, these two phenomena—metastasis and cachexia—should be modelled in parallel, highlighting the overlapping pathways between them. To sum up, this review aims to contribute to rethinking and possibly switching the models currently used for cachexia research, to hopefully obtain better and more translational outcomes.
Predictivity of bioimpedance phase angle for incident disability in older adults
Authors: Uemura Kazuki , Doi Takehiko , Tsutsumimoto Kota , Nakakubo Sho , Kim Min‐Ji , Kurita Satoshi , Ishii Hideaki , Shimada Hiroyuki
Published: August 2019

Background

Bioelectrical impedance analysis (BIA)‐derived phase angle is expected to be an efficient prognostic marker of health adverse events with aging as an alternative of muscle mass. We aimed to examine the predictive ability of phase angle for incident disability in community‐dwelling elderly and determine the optimal cut‐off values.

Methods

Community‐dwelling elderly aged ≥65 years (n = 4452; mean age = 71.8 ± 5.3 years, 48.3% women) without disability at baseline participated in this prospective cohort study. Phase angle and appendicular skeletal muscle mass (ASM) were examined using a multi‐frequency BIA at baseline. Other potential confounding factors (demographics, cognitive function, depressive symptoms, medications, and physical performance) were also assessed. Incident disability was monitored on the basis of long‐term care insurance certification.

Results

Over a follow‐up of 24 months, 4.0% (n = 174) experienced disability, with an overall incidence rate of 20.6 per 1000 person‐years. The Cox hazard regression analysis showed that phase angle, as a continuous variable, was independently associated with incident disability after adjusting the covariates [male: hazard ratios (HRs) = 0.61, 95% confidence interval (CI) = 0.37–0.98; female: HR = 0.58, 95% CI = 0.37–0.90], although body mass index adjusted ASM was not. Receiver operating characteristic analysis indicated moderate predictive abilities of phase angle for incident disability [male: area under the receiver operating characteristic curve (AUC) = 0.76, 95% CI = 0.70–0.83; female: AUC = 0.71, 95% CI = 0.65–0.76], while those of body mass index adjusted ASM were low (male: AUC = 0.59, 95% CI = 0.521–0.66; female: AUC = 0.58, 95% CI = 0.52–0.63). Multivariate Cox regression analysis showed that low phase angle categorized by cut‐off value (male, ≤4.95°; female, ≤4.35°) was independently related to increased risk of incident disability (HR = 1.95, 95% CI = 1.37–2.78).

Conclusions

Lower phase angle independently predicts the incident disability separately from known risk factors. BIA‐derived phase angle can be used as a valuable and simple prognostic tool to identify the elderly at risk of disability as targets of preventive treatment.
The wing pattern of Hydriomena Hübner, [1825] (Lepidoptera: Geometridae: Larentiinae) lacks a predictable relationship with venation
Authors: Schachat Sandra R.
Published: August 2019

Two simple models have been successfully applied to predict the relationship between wing pattern and venation in various lineages of Lepidoptera. However, neither of these models holds for the geometrid genus Hydriomena Hübner, 1825. Wing patterns in Hydriomena were studied intensively during the 1920s after the description of the nymphalid groundplan, an idealized schematic that outlines the primary elements of butterfly wing patterns; geometrids strongly resemble butterflies and, until recently, were considered to be among their closest relatives. The evolution of wing pattern in Geometridae has been neglected since the 1930s. Here, the relationship between wing pattern and venation is examined for Hydriomena costipunctata Barnes and McDunnough, 1912 and the Hydriomena speciosata (Packard, 1873) group. These two lineages have some of the simplest wing patterns in Hydriomena, consisting of large, well‐defined dark and light pattern elements. The relationship between wing pattern and venation varies considerably within and between these lineages and can even vary between the right and left wings on the same individual. Although many different wing patterns were observed among the individuals examined for this study, not one can be reconciled with either of the models that successfully predict the relationship between wing pattern and venation in many other groups of Lepidoptera. This suggests that bands occurring on the wings of Hydriomena are not homologous with those on the wings of butterflies or of Acronictinae (Macroheterocera: Noctuidae), the only other two obtectomeran lineages for which the relationship between wing pattern and venation has been examined in recent years.
Metabolic and Inflammatory Effects of an ω‐3 Fatty Acid–Based Eucaloric Ketogenic Diet in Mice With Endotoxemia
Authors: Anez‐Bustillos Lorenzo , Dao Duy T. , Finkelstein Adam , Pan Amy , Cho Bennet S. , Mitchell Paul D. , Gura Kathleen M. , Bistrian Bruce R. , Puder Mark
Published: August 2019

Background

Dietary strategies can aid in the management of critically ill patients. Very‐low‐carbohydrate diets have been shown to improve glucose control and the inflammatory response. We aimed to determine the effects of a eucaloric ketogenic diet (EKD) enriched with ω‐3 fatty acids (O3KD) on glucose levels and inflammation in mice with endotoxemia.

Methods

Adult mice were fed 1 of 3 diets (control diet [CD], EKD, or O3KD). After 4 weeks, each group received saline or Escherichia coli lipopolysaccharide (LPS) (5 mg/kg) intraperitoneally during the postprandial (PPP) or postabsorptive (PAP) periods. Blood glucose was measured at 0, 15, 30, 60, 90, 120, 180, and 240 minutes. Serum tumor necrosis factor (TNF)‐α and interleukin (IL) 6 were measured by enzyme‐linked immunosorbent assay. Distribution of serum fatty acids was determined by gas liquid chromatography. Hepatic expression of genes involved in inflammation, as well as glucose and lipid metabolism, were determined by quantitative polymerase chain reaction.

Results

During the PPP, glucose curves were comparable among the experimental groups. During the PAP, EKD showed a more pronounced increase in glucose levels at the first hour after LPS challenge compared with the CD‐LPS group. During the PAP, IL6 was lower in O3KD‐LPS compared with CD‐LPS and EKD‐LPS groups. These differences disappeared in the PPP. Similarly, TNF‐α was lower in the O3KD‐LPS group compared with the EKD‐LPS group. The O3KD significantly increased the serum levels of the ω‐3 eicosapentaenoic and docosahexaenoic acids and decreased the ω‐6 arachidonic acid.

Conclusion

An O3KD leads to reduced inflammation and maintains glucose homeostasis in mice with endotoxemia.
MicroRNA‐379 inhibits laryngeal carcinoma cell proliferation and invasion through directly targeting TCF‐4
Authors: Wei Jin‐Long , Zhang Liang , Zhao Zhi‐Ming , Zhao Yu‐Zhu , Fu Qiang , Yang Yan
Published: August 2019

The expression pattern, functions, and detailed regulatory mechanisms of miR‐379 in laryngeal carcinoma remain unknown. In the present study, we aimed to uncover novel potential miR‐379 targets and shed light on its roles in laryngeal carcinoma. The expression level of miR‐379 was measured based on the data obtained from the TCGA database and the cell lines. After miR‐379 mimic transfection, cell proliferation, invasion and migration assay, and wound‐healing assay in HEp‐2 cell line were implemented to evaluate the effects of miR‐379 on laryngeal carcinoma in vitro. The target genes for miR‐379 in silico were predicted and validated using luciferase reporter assay. The miR‐379 expression level was reduced in laryngeal carcinoma tissues and cell lines. Moreover, miR‐379 overexpression inhibited the cell proliferation, migration, and invasion of laryngeal carcinoma cells. TCF‐4 was detected as a direct target of miR‐379 in laryngeal carcinoma. Furthermore, restored TCF‐4 expression rescued the inhibitory roles of miR‐379 overexpression on cell proliferation, migration, and invasion.Our study for the first time demonstrated that miR‐379/TCF‐4 might involve in the progression of laryngeal carcinoma, and miR‐379 appears to serve as a novel tumor suppressor in laryngeal carcinoma.
Is Portal Inflow Modulation Always Necessary for Successful Utilization of Small Volume Living Donor Liver Grafts?
Authors: Soin Arvinder Singh , Yadav Sanjay Kumar , Saha Sujeet Kumar , Rastogi Amit , Bhangui Prashant , Srinivasan Thiagarajan , Saraf Neeraj , Choudhary Narendra S. , Saigal Sanjeev , Vohra Vijay
Published: August 2019

Although the well‐accepted lower limit of the graft‐to‐recipient weight ratio (GRWR) for successful living donor liver transplantation (LDLT) remains 0.80%, many believe grafts with lower GRWR may suffice with portal inflow modulation (PIM), resulting in equally good recipient outcomes. This study was done to evaluate the outcomes of LDLT with small‐for‐size grafts (GRWR <0.80%). Of 1321 consecutive adult LDLTs from January 2012 to December 2017, 287 (21.7%) had GRWR <0.80%. PIM was performed (hemiportocaval shunt [HPCS], n = 109; splenic artery ligation [SAL], n = 14) in 42.9% patients. No PIM was done if portal pressure (PP) in the dissection phase was <16 mm Hg. Mean age of the cohort was 49.3 ± 9.1 years. Median Model for End‐Stage Liver Disease score was 14, and the lowest GRWR was 0.54%. A total of 72 recipients had a GRWR <0.70%, of whom 58 underwent HPCS (1 of whom underwent HPCS + SAL) and 14 underwent no PIM, whereas 215 had GRWR between 0.70% and 0.79%, of whom 51 and 14 underwent HPCS and SAL, respectively. During the same period, 1034 had GRWR ≥0.80% and did not undergo PIM. Small‐for‐size syndrome developed in 2.8% patients. Three patients needed shunt closure at 1 and 4 weeks and 60 months. The 1‐year patient survival rates were comparable. In conclusion, with PIM protocol that optimizes postperfusion PP, low‐GRWR grafts can be used for appropriately selected LDLT recipients with acceptable outcomes.
Macrophage HIF‐2α regulates tumor‐suppressive Spint1 in the tumor microenvironment
Authors: Susen Rosa M. , Bauer Rebekka , Olesch Catherine , Fuhrmann Dominik C. , Fink Annika F. , Dehne Nathalie , Jain Arpit , Ebersberger Ingo , Schmid Tobias , Brüne Bernhard
Published: August 2019

In solid tumors, tumor‐associated macrophages (TAMs) commonly accumulate within hypoxic areas. Adaptations to such environments evoke transcriptional changes by the hypoxia‐inducible factors (HIFs). While HIF‐1α is ubiquitously expressed, HIF‐2α appears tissue‐specific with consequences of HIF‐2α expression in TAMs only being poorly characterized. An E0771 allograft breast tumor model revealed faster tumor growth in myeloid HIF‐2α knockout (HIF‐2αLysM−/−) compared with wildtype (wt) mice. In an RNA‐sequencing approach of FACS sorted wt and HIF‐2α
LysM−/− TAMs, serine protease inhibitor,
Kunitz type‐1 (
Spint1) emerged as a promising candidate for HIF‐2α‐dependent regulation. We validated reduced
Spint1 messenger RNA expression and concomitant Spint1 protein secretion under hypoxia in HIF‐2α‐deficient bone marrow–derived macrophages (BMDMs) compared with wt BMDMs. In line with the physiological function of Spint1 as an inhibitor of hepatocyte growth factor (HGF) activation, supernatants of hypoxic HIF‐2α knockout BMDMs, not containing Spint1, were able to release proliferative properties of inactive pro‐HGF on breast tumor cells. In contrast, hypoxic wt BMDM supernatants containing abundant Spint1 amounts failed to do so. We propose that Spint1 contributes to the tumor‐suppressive function of HIF‐2α in TAMs in breast tumor development.
Examining boys’ and girls’ health‐related quality of life from the first to the third year of upper secondary school: A prospective longitudinal study
Authors: Langeland Ingrid Oma , Sollesnes Ragnhild , Nilsen Roy Miodini , Almenning Grethe , Langeland Eva
Published: August 2019

Aim

To examine differences in health‐related quality of life between boys and girls in the first and third years of upper secondary school.

Design

Prospective longitudinal study.

Methods

The KIDSCREEN‐10 was used to assess health‐related quality of life. Differences in health‐related quality of life over time were estimated using a linear mixed‐effects model for correlated measurements.

Results

In the first‐year boys (N = 168) and girls (N = 228) reported a mean health‐related quality of life score of 76.3 (SD 10.7) and 69.8 (SD 11.5), respectively. In the third year, the mean health‐related quality of life score for boys and girls was 73.5 (SD 12.4) and 65.7 (SD 13.3), respectively. Boys had a significant decrease in health‐related quality of life mean score of −2.6 and girls a significant decrease of −3.8 (p < .001) over the 3‐year period. There was no significant difference between boys’ and girls’ health‐related quality of life changes (p = .39).
Longitudinal development of cancer‐related fatigue and physical activity in childhood cancer patients
Authors: Van Dijk‐Lokkart Elisabeth M. , Steur Lindsay M. H. , Braam Katja I. , Veening Margreet A. , Huisman Jaap , Takken Tim , Bierings Marc , Merks Johannes H. , Van den Heuvel‐Eibrink Marry M. , Kaspers Gertjan J. L. , Van Dulmen‐den Broeder Eline , Van Litsenburg Raphaële R. L.
Published: August 2019

Purpose

Cancer‐related fatigue is one of the most distressing side effects of childhood cancer treatment. Physical activity can decrease fatigue and has positive effects on other health outcomes. Most research on physical activity pertains to adults, and the few studies that focus on children have limited follow‐up time. This study evaluates cancer‐related fatigue in children and its association with physical activity over a one‐year time period.

Methods

Sixty‐eight children with cancer (7–18 years) were recruited during or within the first year after treatment. Physical activity (Actical activity monitor) and cancer‐related fatigue (Pediatric Quality‐of‐Life Questionnaire Multidimensional Fatigue Scale (PedsQL‐MFS), self‐ and parent‐ reports) were assessed at baseline, 4 months, and 12 months. PedsQL‐MFS scores were compared with Dutch norms. Longitudinal association of cancer‐related fatigue with physical activity was evaluated (No. NTR 1531).

Results

Generally, PedsQL‐MFS scores were worse than norms at baseline and 4 months, and recovered by 12 months except for the parent‐proxy scores in adolescents. Younger children (≤12 years) self‐reported comparable or better scores than norms. Physical activity generally improved over time, but patients mostly remained sedentary. During follow‐up, increased physical activity was associated with less cancer‐related fatigue.

Conclusion

Cancer‐related fatigue in children improves over time, and increased physical activity is associated with less cancer‐related fatigue. Given the sedentary lifestyle of this population, the positive effect of physical activity on cancer‐related fatigue, and the many other health benefits of an active lifestyle, it is important to stimulate physical activity in childhood cancer patients and survivors.