bluuebunny/crossref_metadata_2025 huggingface dataset:
Birth of primate comparative anatomy
Authors: Wood Bernard
Published: January 2020

In 1698, a creature with a perplexing mix of human and “ape” features died in London. Brought back to England by merchants who had acquired it during a trading mission to West Africa, it attracted the attention of the Royal Society, and after the death of what we now know was a juvenile chimpanzee, Edward Tyson, a distinguished physician/anatomist, was commissioned to undertake its dissection. Tyson, who was assisted by William Cowper, prepared a detailed written and graphic description of their meticulous dissection, and this forms the major part of his 1699 publication Orang‐outang sive Homo sylvestris: or The Anatomy of a Pygmie compared with that of a Monkey, an Ape, and a Man. Tyson records the many ways his “pygmie” resembled, and differed from, modern humans, including acute assessments of its brain and pelvic anatomy. Tyson's monograph is a text‐book example of the comparative method. He, and it, deserve more recognition.
Using the yield curve to forecast economic growth
Authors: Yang Parley Ruogu
Published: January 2020

This paper finds the yield curve to have a well‐performing ability to forecast the real gross domestic product growth in the USA, compared to professional forecasters and time series models. Past studies have different arguments concerning growth lags, structural breaks, and ultimately the ability of the yield curve to forecast economic growth. This paper finds such results to be dependent on the estimation and forecasting techniques employed. By allowing various interest rates to act as explanatory variables and various window sizes for the out‐of‐sample forecasts, significant forecasts from many window sizes can be found. These seemingly good forecasts may face issues, including persistent forecasting errors. However, by using statistical learning algorithms, such issues can be cured to some extent. The overall result suggests, by scientifically deciding the window sizes, interest rate data, and learning algorithms, many outperforming forecasts can be produced for all lags from one quarter to 3 years, although some may be worse than the others due to the irreducible noise of the data.
A perspective on fossil fuel based flue gas emission reduction technologies
Authors: Yalcin Sefa , Konukman Alp Er Ş. , Midilli Adnan
Published: January 2020

The aim of this paper is to specify the role of coal‐fired power plants (CFPPs) in the formation of global emissions/harmful pollutants and to discuss the benefits of current and future technologies to minimize environmental damage. In this regard, pollutant/emission reduction technologies from CFPPs are discussed in detail by considering the environmental and global warming aspects. Pollutant gases from CFPPs around the globe have always been the most important source of environmental concern in societies. In particular, due to the burning of the coal without taking the necessary precautions, the nitrogen in the coal and combustion air and the combustible sulfur components in the coal content are oxidized and released to the atmosphere as nitrogen oxides (NOx) and sulfur oxides (SOx). Another pollutant from power plants is carbon monoxide (CO). CO is a colorless, odorless, poisonous gas that can remain in the atmosphere for a long time. In addition, significant amounts of carbon dioxide (CO2) occur by virtue of the combustion of coal. CO2 emission is in the class of greenhouse gases causing global warming. As a result of this study, the factors causing the formation of harmful pollutants in CFPPs are determined and present and potential suggestions are provided for the environmental sustainability of such facilities. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.
Depositional style changes during the Permo‐Carboniferous–Early Jurassic evolution of the Central Kalahari Karoo Sub‐basin, Botswana
Authors: Bordy Emese M.
Published: January 2020

The Permo‐Carboniferous–Lower Jurassic Karoo succession in the Central Kalahari Karoo Sub‐basin of Botswana is largely confined to the subsurface, and contains coal, coalbed methane and groundwater resources, similar to other Karoo strata throughout southern Africa. Characterization of the stratigraphic architecture (i.e., spatiotemporal stacking character of sedimentary facies) is essential for various aspects of subsurface resource prediction (e.g., resource parameters; reservoir architecture; mining feasibility). This study uses sedimentary facies analysis on borehole cores from central Botswana and sequence stratigraphic principles to resolve large‐scale depositional style changes during the evolution of the greater Kalahari Karoo Basin in southwestern Gondwana. The results show that changes in the Karoo stratigraphic architecture define two, large‐scale overall fining‐upward depositional sequences (i.e., Lower and Upper Karoo) that are marked by regional subaerial unconformities. These regionally mappable depositional sequences contain pairs of high‐ to low‐amalgamation units, which are typified by stacked, multistorey sandstone bodies, succeeded by finer grained units that are sometimes rich in coal (e.g., the Dukwi‐Makoro‐Kamotaka vs. the Morupule‐Serowe‐Tlhabala formations in the Lower Karoo; the lower versus upper Mosolotsane‐Ntane formations in the Upper Karoo). The large‐scale depositional style changes, reflecting base‐level fluctuations and variation in the balance between accommodation and sediment supply, resulted from climatic changes (e.g., Permo‐Carboniferous deglaciation), tectonic events (e.g., regional pre‐Mosolotsane uplift event), and marine incursions. The latter is documented, for the first time, via the marine‐influenced ichnofauna in the uppermost Ecca Group. Further refining this initial sequence stratigraphic framework for the Botswanan Karoo will require acquisition of radioisotopic dates (e.g., U–Pb zircon ages) and modern seismic reflection data.
Epigenomic and transcriptional determinants of microglial cell identity
Authors: Gosselin David
Published: January 2020

Microglia perform multiple tasks that are essential to ensure proper cerebral functions, including synaptic remodeling, clearance of molecular debris, prevention of infections, and so forth. Furthermore, accumulating genetic and pathological evidence implicates microglial cell activity in the etiology of numerous neurodegenerative diseases and psychiatric disorders. Given this, efforts aimed at understanding the molecular mechanisms underlying microglial cell functions hold great potential for the development of novel therapies for various conditions affecting the central nervous system. In that regard, the application of paradigms in epigenomics to study transcription in microglia has provided significant insights into the molecular mechanisms that control the ontogeny and functions of these cells. With a focus on the roles of genomic regulatory elements and the epigenetic marks that control microglial gene expression, we review here recent key advancements in our comprehension of the epigenomic and transcriptional mechanisms that enable microglial cell development and activity.
Lifetime history of traumatic brain injury is associated with increased loneliness in adults: A US nationally representative study
Authors: Kumar Raj G. , Ornstein Katherine A. , Bollens‐Lund Evan , Watson Eric M. , Ankuda Claire K. , Kelley Amy S. , Dams‐O'Connor Kristen
Published: January 2020

Background/Objectives

An estimated 55 million individuals worldwide live with chronic disability associated with traumatic brain injury (TBI), which may include cognitive, behavioral, and social impairments. Reduced participation in social activities is common after TBI; however, few studies have evaluated loneliness among survivors of TBI. The current study aimed to evaluate the association between history of TBI and loneliness and to identify mediators of this association.

Methods/Design

Retrospective cohort study. Nationally representative sample of N = 724 adults over age 50 years (Health and Retirement Study). Loneliness was evaluated using the 11‐item Revised University of California Los Angeles (R‐UCLA) Loneliness Scale (range 11‐33). Lifetime history of TBI evaluated retrospectively using the Ohio State University TBI Identification Method. We included the following covariates: age, sex, race, and education; and mediators: depressive symptoms, number of comorbidities, chronic pain, difficulty with activities of daily living, and social network index.

Results

History of TBI was associated with a 1.28‐point (95% CI, 0.46‐2.11;P < .05; Cohen's D = 0.284) increase in R‐UCLA Loneliness Scale scores after covariate adjustment. Individuals with more recent injuries (within 10 years) and multiple lifetime TBIs reported the highest loneliness scores. In the structural equation model, depressive symptoms partially mediated the relationship between TBI and loneliness. All models were adjusted for US population sampling weights.

Conclusions

History of TBI was associated with greater loneliness compared with individuals without TBI in a representative sample of US adults. Managing depressive symptoms and medical consequences of TBI may be a target to ameliorate reporting of loneliness in this population.
In vivo anatomical mapping of human locus coeruleus functional connectivity at 3 T MRI
Authors: Liebe Thomas , Kaufmann Jörn , Li Meng , Skalej Martin , Wagner Gerd , Walter Martin
Published: January 2020

The locus coeruleus (LC) is involved in numerous crucial brain functions and several disorders like depression and Alzheimer's disease. Recently, the LC resting‐state functional connectivity (rs‐fc) has been investigated in functional MRI by calculating the blood oxygen level–dependent (BOLD) response extracted using Montreal Neurological Institute (MNI) space masks. To corroborate these results, we aimed to investigate the LC rs‐fc at native space by improving the identification of the LC location using a neuromelanin sensitive sequence. Twenty‐five healthy male participants (mean age 24.8 ± 4.2) were examined in a Siemens MAGNETOM Prisma 3 T MRT applying a neuromelanin sensitive T1TSE sequence and functional MRI. We compared the rs‐fc of LC calculated by a MNI‐based approach with extraction of the BOLD signal at the exact individual location of the LC after applying CompCor and field map correction. As a measure of advance, a marked increase of regional homogeneity (ReHo) of time series within LC could be achieved with the subject‐specific approach. Furthermore, the methods differed in the rs‐fc to the right temporoparietal junction, which showed stronger connectivity to the LC in the MNI‐based method. Nevertheless, both methods comparably revealed LC rs‐fc to multiple brain regions including ACC, bilateral thalamus, and cerebellum. Our results are relevant for further research assessing and interpreting LC function, especially in patient populations examined at 3 T MRI.
Motor skills predict faux pas understanding in middle childhood
Authors: Tenenbaum Harriet R. , Leonard Hayley C.
Published: January 2020

This study examined emotion understanding and motor skills as predictors of children's understanding of faux pas. Faux paus situations are those in which someone causes unintentional offence or behaves inappropriately. Understanding of faux pas requires knowledge of social norms in specific situations as well as emotion understanding. Misunderstanding faux pas can prevent smooth social functioning. Fifty‐six children (aged 7; 0 to 9; 11 years) completed a measure of faux pas understanding, emotion understanding, and motor skills. Children's faux pas understanding, emotion understanding, and motor skills were all related to each other. However, when age, motor skills, and emotion understanding were entered into a regression to predict faux pas understanding, only motor skills predicted understanding of faux pas. The findings are discussed in relation to potential pathways between motor skills and social understanding.

Highlights

We examined relations between emotion understanding (Test of Emotion Comprehension), motor skills (Movement Assessment Battery for Children), and faux pas.

All three variables were related, but in a multiple regression with age, only motor skills predicted children's faux pas understanding.

Motor skills may contribute to children's smooth social functioning.
Regulation of immune cell metabolism by cancer cell oncogenic mutations
Authors: Madi Alaa , Cui Guoliang
Published: January 2020

In noncancerous tissues, neighboring cells coexist in metabolic harmony. This metabolic harmony is disrupted in cancerous tissues, often accompanied by genetic mutations. Tumor cells fundamentally change the metabolite profiles in the tumor microenvironment to favor their own growth. In this review, we will discuss several examples in which genetic mutations reprogram tumor cell metabolic pathways, leading to the consumption of essential nutrients in the tumor microenvironment, production of toxic byproducts, and suppression of antitumor immune cell metabolic fitness and tumor‐killing function. Finally, we will briefly discuss how immune checkpoint blockade overcomes the metabolic suppression of tumor‐infiltrating immune cells.
Uterine tamponade in postpartum hemorrhage: A new handmade intrauterine balloon
Authors: Alves Álvaro Luiz Lage , Senra Janaína Campos , Gonçalves Caroline Reis , Ribeiro Bruna Roque , de São José Carolina Nogueira , Candido Eduardo Batista , Silva Lucas Barbosa , Silva‐Filho Agnaldo Lopes
Published: January 2020

The Alves handmade intrauterine balloon is a new device which shows promising results for the effective treatment of PPH with intrauterine tamponade. The Alves handmade IUB components are affordable and more resistant to obstruction than other handmade IUBs.
Combining Frailty and Trabecular Bone Score Did Not Improve Predictive Accuracy in Risk of Major Osteoporotic Fractures
Authors: Li Guowei , Leslie William D , Kovacs Christopher S , Prior Jerilynn , Josse Robert G , Towheed Tanveer , Davison K Shawn , Thabane Lehana , Papaioannou Alexandra , Levine Mitchell AH , Goltzman David , Zeng Jie , Qi Yong , Tian Junzhan , Adachi Jonathan D ,   for the Canadian Multicentre Osteoporosis Study (CaMos) Research Group
Published: January 2020

It is recognized that the trabecular bone score (TBS) provides skeletal information, and frailty measurement is significantly associated with increased risks of adverse health outcomes. Given the suboptimal predictive power in fracture risk assessment tools, we aimed to evaluate the combination of frailty and TBS regarding predictive accuracy for risk of major osteoporotic fracture (MOF). Data from the prospective longitudinal study of CaMos (Canadian Multicentre Osteoporosis Study) were used for this study. TBS values were estimated using lumbar spine (L1 to L4) dual-energy X-ray absorptiometry (DXA) images; frailty was evaluated by a frailty index (FI) of deficit accumulation. Outcome was time to first incident MOF during the follow-up. We used the Harrell's C-index to compare the model predictive accuracy. The Akaike information criterion, likelihood ratio test, and net reclassification improvement (NRI) were used to compare model performances between the model combining frailty and TBS (subsequently called “FI + TBS”), FI-alone, and TBS-alone models. We included 2730 participants (mean age 69 years; 70% women) for analyses (mean follow-up 7.5 years). There were 243 (8.90%) MOFs observed during follow-up. Participants with MOF had significantly higher FI (0.24 versus 0.20) and lower TBS (1.231 versus 1.285) than those without MOF. FI and TBS were significantly related with MOF risk in the model adjusted for FRAX with bone mineral density (BMD) and other covariates: hazard ratio (HR) = 1.26 (95% confidence interval [CI] 1.11–1.43) for per-SD increase in FI; HR = 1.38 (95% CI 1.21–1.59) for per-SD decrease in TBS; and these associations showed negligible attenuation (HR = 1.24 for per-SD increase in FI, and 1.35 for per-SD decrease in TBS) when combined in the same model. Although the model FI + TBS was a better fit to the data than FI-alone and TBS-alone, only minimal and nonsignificant enhancement of discrimination and NRI were observed in FI + TBS. To conclude, frailty and TBS are significantly and independently related to MOF risk. Larger studies are warranted to determine whether combining frailty and TBS can yield improved predictive accuracy for MOF risk. © 2020 American Society for Bone and Mineral Research.
Arrhythmogenic risks of stem cell replacement therapy for cardiovascular diseases
Authors: Chen Kang , Huang Yuting , Singh Radhika , Wang Zack Z.
Published: January 2020

Ischemic heart disease and congestive heart failure are major contributors to high morbidity and mortality. Approximately 1.5 million cases of myocardial infarction occur annually in the United States; the yearly incidence rate is approximately 600 cases per 100,000 people. Although significant progress to improve the survival rate has been made by medications and implantable medical devices, damaged cardiomyocytes are unable to be recovered by current treatment strategies. After almost two decades of research, stem cell therapy has become a very promising approach to generate new cardiomyocytes and enhance the function of the heart. Along with clinical trials with stem cells conducted in cardiac regeneration, concerns regarding safety and potential risks have emerged. One of the contentious issues is the electrical dysfunctions of cardiomyocytes and cardiac arrhythmia after stem cell therapy. In this review, we focus on the cell sources currently used for stem cell therapy and discuss related arrhythmogenic risk.
Long noncoding RNA LINC01278 favors the progression of osteosarcoma via modulating miR‐133a‐3p/PTHR1 signaling
Authors: Qu Zhigang , Li Shenglong
Published: January 2020

As one of the most aggressive malignancies, osteosarcoma has high risks of death. Although long noncoding RNAs (lncRNAs) may promote the osteosarcoma progression as verified, the potential molecular mechanism of lncRNAs in osteosarcoma remains unknown. Herein, we analyzed lncRNA microarray of osteosarcoma and selected LINC01278 as the study object. Then, we found that the expression of LINC01278 tested by quantitative reverse‐transcription polymerase chain reaction was enhanced in tumor tissues compared with the para‐carcinoma tissues and related to clinical stage, distant metastasis in osteosarcoma. In addition, the clinical outcomes were poor in osteosarcoma patients with high LINC01278 level. Moreover, LINC01278 promoted proliferation and restrained apoptosis in osteosarcoma cells. Afterward, mechanistic studies turned out that LINC01278 was a competing endogenous RNA of parathyroid hormone type 1 receptor (PTHR1) in osteosarcoma by sponging miR‐133a‐3p, which was considered as a tumor inhibitor in osteosarcoma. Furthermore, PTHR1 downregulation restored the impacts of inhibited miR‐133a‐3p on the processes in osteosarcoma cells. Our findings clarified that the carcinogenic effect of LINC01278 in osteosarcoma was mediated through miR‐133a‐3p/PTHR1 signaling, creating a novel insight into good targets for the therapy and prognosis of osteosarcoma.
Exosome‐mediated transfer of long noncoding RNA H19 induces doxorubicin resistance in breast cancer
Authors: Wang Xinxing , Pei Xinhong , Guo Guangcheng , Qian Xueke , Dou Dongwei , Zhang Zhe , Xu Xiaodong , Duan Xin
Published: January 2020

Development of the acquired resistance is one major obstacle during chemotherapy for cancer patients. Exosomes mediate intercellular communication and cause environmental changes in tumor progression by transmitting active molecules. In this study, the role of long noncoding RNA H19 within exosomes is elucidated in terms of regulating doxorubicin (DOX) resistance of breast cancer. As a result, increased H19 expression was observed in DOX‐resistant breast cancer cells in comparison with the corresponding parental cells. Suppression of H19 significantly lowered DOX resistance by decreasing cell viability, lowering colony‐forming ability, and inducing apoptosis. Moreover, extracellular H19 could be moved to sensitive cells via being incorporated into exosomes. Treating sensitive cells with exosomes from resistant cells increased the chemoresistance of DOX, while downregulation of H19 in sensitive cells abated this effect. Taken together, H19 could be delivered by exosomes to sensitive cells, leading to the dissemination of DOX resistance. Our finding highlights the potential of exosomal H19 as a molecular target to reduce DOX resistance.
Synthesis, biological evaluation and molecular docking study of dihydropyrimidine derivatives as potential anticancer agents
Authors: Safari Sahand , Ghavimi Reza , Razzaghi‐Asl Nima , Sepehri Saghi
Published: January 2020

A series of dihydropyrimidine analogues were prepared via one‐pot Biginelli three‐component condensation reaction and characterized by NMR, FT‐IR, MS spectra, and element analysis. Subsequently, they were screened for in vitro anticancer effect. These analogues revealed good cytotoxic activity against three human cancer cell lines including MCF‐7, HepG‐2, and A549. Among these analogues, compounds 4d and 4h were the most potent against three cell lines. Cell viability assays indicated 4a and 4c had lower cytotoxicity. In vitro cytotoxicity study on all synthesized compounds demonstrated that introduction of electron withdrawing substituents on C4 position of phenyl ring of dihydropyrimidine contributed to the antiproliferative potency. Moreover, in silico molecular docking results stipulated a sign of good correlation between experimental activity and calculated binding affinity. It proved 4d and 4h as the strongest compounds. Binding modes of analogues proposed the involvement of hydrophobic interactions and hydrogen bonds with Eg5 active site. Structure activity relationship studies indicated that incorporating electron withdrawing substituents on C4 position of phenyl ring of dihydropyrimidine are important for this biological activity.
Synthesis, characterization, and antiplasmodial efficacy of sulfonamide‐appended [1,2,3]‐triazoles
Authors: Batra Neha , Rajendran Vinoth , Wadi Ishan , Lathwal Ankit , Dutta Roshan Kumar , Ghosh Prahlad C. , Gupta Rinkoo D. , Nath Mahendra
Published: January 2020

A series of benzenesulfonamide‐appended [1,2,3]‐triazole hybrids was synthesized by using [3 + 2] cycloaddition of primary, secondary, and tertiary sulfonamide azides with various phenoxymethylacetylenes under click reaction conditions. After structural characterization, the compounds were subjected to in‐silico absorption, distribution, metabolism, excretion and toxicity (ADMET) screening to evaluate their drug‐likeness and other pharmacokinetic parameters. Furthermore, their in vitro antiplasmodial potential was assessed against Plasmodium falciparum (3D7) strain, and some of the synthesized compounds displayed promising antimalarial potency. On cytotoxicity evaluation using MTT cell viability assay, the most active candidate N‐(4,6‐dimethylpyridin‐2‐yl)‐4‐(4‐(4‐nitrophenoxy)methyl)‐1H‐[1,2,3]‐triazol‐1‐yl)benzenesulfonamide (14; IC50 6.2 μg/mL) demonstrated CC50 7.5 μg/mL against human hepatocarcinoma (HUH‐7) cells.
One‐pot synthesis and biological evaluation of novel 4‐[3‐fluoro‐4‐(morpholin‐4‐yl)]phenyl‐1H‐1,2,3‐triazole derivatives as potent antibacterial and anticancer agents
Authors: Narsimha Sirassu , Nukala Sathesh Kumar , Savitha Jyostna T. , Ravinder M. , Srinivasa Rao M. , Vasudeva Reddy N.
Published: January 2020

In search of better antibacterial and anticancer agents, a series of novel 4‐[3‐fluoro‐4‐(morpholin‐4‐yl)]phenyl‐1H‐1,2,3‐triazole derivatives were synthesized (6a‐l and 8a‐j) by using 3‐fluoro‐4‐morpholinoaniline, alkyne, and triflyl azide via an in situ generated 4‐(4‐azido‐2‐fluorophenyl)morpholine and evaluated for their antibacterial and anticancer activity in vitro. Antibacterial activity against three G+ bacterial strains and anticancer activity against breast cancer cell line (MCF‐7) and cervical carcinoma cell line (HeLa) was evaluated. Among all the tested compounds, 6h, 6i, and 8b exhibited potent antibacterial activity against tested gram‐positive bacterial strains. The anticancer activity screening results of 8f, 8h, and 8i exhibited potent cytotoxic activity against two cancer cell lines with IC50 values nearer to the standard drug, doxorubicin. The remaining compounds have shown good to moderate activity against the tested cell lines. On the basis of the results obtained, a structure‐activity relationship (SAR) is discussed.
The 2019‐new coronavirus epidemic: Evidence for virus evolution
Authors: Benvenuto Domenico , Giovanetti Marta , Ciccozzi Alessandra , Spoto Silvia , Angeletti Silvia , Ciccozzi Massimo
Published: January 2020

There is a worldwide concern about the new coronavirus 2019‐nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019‐nCoV, 12 whole genome sequences of 2019‐nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS‐like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid and the spike glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019‐nCoV significantly clustered with bat SARS‐like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019‐nCoV is distinct from SARS virus, probably trasmitted from bats after mutation conferring ability to infect humans.
Induction of cross‐neutralizing antibodies by sequential immunization with heterologous papillomavirus L1VLPs and its implications for HPV prophylactic vaccines
Authors: Zhang Ting , Chen Xue , Liao Guoyang , Hu Meili , Xu Jianqing , Xu Xuemei
Published: January 2020

Sequential immunization with antigens from different strains of HIV‐1, influenza viruses or dengue viruses induced cross‐neutralizing antibodies and enhanced the antibody responses against previous antigens. The characteristics of neutralizing antibodies induced by sequential immunization with different types of human papillomavirus (HPV) L1 virus‐like particles (L1VLPs) are unclear. In this study, mice were primed with one or two types (HPV‐16 or HPV16/18) of L1VLPs, then boosted sequentially with HPV6/18/45/11/31/58 or HPV6/45/11/31/58 L1VLPs, and sera were analyzed with HPV pseudovirus‐based neutralization assay. The results showed that neutralizing activities against earlier immunized vaccine types were enhanced gradually by subsequent immunizations, and low levels of neutralizing activities against nonvaccine types (HPV33/35/52/59/68) were also observed. After absorbing the immune sera with vaccine‐type (HPV16/18/45) L1VLPs, neutralizing activities against tested priming and boosting types (HPV16/18/58) decreased significantly, and that against nonvaccine type (HPV‐33) was also partially eliminated. Moreover, neutralizing activities against vaccine types (HPV16/58) were significantly reduced after absorbing with nonvaccine‐type VLPs (HPV33/52). These data suggest that cross‐neutralizing epitopes exist among different HPV L1VLPs. The cross‐neutralizing activities against nonvaccine types and the enhanced neutralizing activities against earlier immunized vaccine types may result from sequential boosting with these cross‐neutralizing epitopes. These observations support early vaccination with more types of L1VLPs derived from HPVs that cause a serious threat to the population.
The construction of a new oncolytic herpes simplex virus expressing murine interleukin‐15 with gene‐editing technology
Authors: Cai Linkang , Hu Han , Duan Haixiao , Li Yuying , Zou Zongxing , Luo Kailun , Zhang Ziyi , Yang Junhan , Jin Jing , Chen Ying , Ke Zonghuang , Fang Zongyao , Liu Qiong , Hong Xiaoqian , Hu Sheng , Liu Binlei
Published: January 2020

The treatment of tumors with oncolytic viruses is an important cancer immunotherapy strategy. Interleukin‐15 (IL‐15) can enhance the antitumor effect of natural killer cells and T cells. An oncolytic herpes simplex type II virus (oHSV2‐mIL‐15CherryFP) expressing mouse IL‐15 was constructed using the CRISPR/Cas9 system, and its antitumor activity in vitro and in vivo was evaluated. In vitro, the mouse interleukin‐15 (mIL‐15) present in the culture supernatant expressed by oHSV2‐mIL‐15CherryFP was able to enhance the killing of CT26‐GFP tumor cells by T cells. In addition, the intratumoral injection of oHSV2‐mIL‐15CherryFP inhibited tumor growth in the CT26‐iRFP and BGC823‐iRFP model. These results indicate that the use of oncolytic herpes simplex virus expressing IL‐15 may be a potential therapeutic strategy in tumor immunotherapy.
Projections of climatic extremes in a data poor transboundary river basin of India and Pakistan
Authors: Aslam Rana A. , Shrestha Sangam , Pal Indrajit , Ninsawat Sarawut , Shanmugam Mohana S. , Anwar Shafiq
Published: January 2020

This study aims to project and characterize the climate extremes in Ravi River Basin (RRB) which is considered as a data poor transboundary basin located in India and Pakistan. Performance of the three GCDs against observation data was evaluated at three stations. A quantile mapping technique was used to correct the biases of four regional climate models (RCMs) and climate extremes were analysed for future period (2020–2095). Seven temperature and rainfall based indices that represent warm and wet characteristics of climate were chosen. Four statistical parameters and spatial maps were evaluated for the base period 1982–2005. The CPC‐NOAA and PU had the best performance for temperature and rainfall data regarding the time series analysis. The quantile mapping improved three important aspects of the climate cycle; the transitions from dry to wet and wet to dry seasons and peaks as well. At spatial scale, quantile mapping well captured the spatial distribution of the eleven indices other than RX1Day, CWD and FD0. The results show that warm and wet extremes will increase in future at 5% significance level across the entire basin with large changes in north east. The changes will be large for RCP8.5 scenario compare to RCP4.5 scenario and choice of the scenarios has dominant contribution in uncertainty than choice of the models.
American Society for Bone and Mineral Research‐Orthopaedic Research Society Joint Task Force Report on Cell‐Based Therapies – Secondary Publication
Authors: O'Keefe Regis J. , Tuan Rocky S. , Lane Nancy E. , Awad Hani A. , Barry Frank , Bunnell Bruce A. , Colnot Céline , Drake Matthew T. , Drissi Hicham , Dyment Nathaniel A. , Fortier Lisa A. , Guldberg Robert E. , Kandel Rita , Little David G. , Marshall Mary F. , Mao Jeremy J. , Nakamura Norimasa , Proffen Benedikt L. , Rodeo Scott A. , Rosen Vicki , Thomopoulos Stavros , Schwarz Edward M. , Serra Rosa
Published: January 2020

Cell‐based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell‐based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web‐based marketing and patient testimonials supporting cell‐based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell‐based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell‐based therapies. The Task Force was charged with defining the state‐of‐the art in cell‐based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell‐based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:485–502, 2020
Value of Nutrition Support Therapy: Impact on Clinical and Economic Outcomes in the United States
Authors: Tyler Renay , Barrocas Albert , Guenter Peggi , Araujo Torres Krysmaru , Bechtold Matthew L. , Chan Lingtak‐Neander , Collier Bryan , Collins Nilsa A. , Evans David C. , Godamunne Karim , Hamilton Cindy , Hernandez Beverly J. D. , Mirtallo Jay M. , Nadeau William J. , Partridge Jamie , Perugini Moreno , Valladares Angel ,   the ASPEN Value Project Scientific Advisory Council
Published: January 2020

Objective

Healthcare leaders seek guidance on prudent investment in programs that improve patient outcomes and reduce costs, which includes the value of nutrition therapy. The purpose of this project was to conduct an evidence review and evaluate claims analyses to understand the financial and quality impact of nutrition support therapy on high‐priority therapeutic conditions.

Methods

Task 1 included a review of existing literature from 2013 to 2018 to identify evidence that demonstrated the clinical and economic impact of nutrition intervention on patient outcomes across 13 therapeutic areas (TAs). In Task 2, analytic claims modeling was performed using the Medicare Parts A and B claims 5% sample dataset. Beneficiaries diagnosed in 5 selected TAs (sepsis, gastrointestinal [GI] cancer, hospital‐acquired infections, surgical complications, and pancreatitis) were identified in the studies from Task 1, and their care costs were modeled based on nutrition intervention.

Results

Beginning with 1099 identified articles, 43 articles met the criteria, with a final 8 articles used for the Medicare claims modeling. As examples of the modeling demonstrated, the use of advanced enteral nutrition formula could save at least $52 million annually in a sepsis population. The total projected annual cost savings from the 5 TAs was $580 million.

Conclusion

Overall, optimization of nutrition support therapy for specific patient populations is estimated to reduce Medicare spending by millions of dollars per year across key TAs. These findings demonstrate the evidence‐based value proposition of timely nutrition support to improve clinical outcomes and yield substantial cost savings.
Raman spectroscopy of poly (methyl methacrylate) under laser shock and static compression
Authors: Chaurasia S. , Rao Usha , Mishra Ajay K. , Sijoy C.D. , Mishra V.
Published: January 2020

Time‐resolved Raman spectroscopy for visualizing molecular fingerprint snapshots at nanosecond time scale is a useful tool for detailed understanding of in situ shock behaviour of materials. This technique was applied to study the changes in molecular vibrations of poly (methyl methacrylate) (PMMA) under laser driven shock compression up to ~1.9 GPa in a confinement geometry. A layered target configuration is used to enhance the shock pressure. The vibrational modes are measured as a function of dynamic shock and static compression. The Grüneisen parameters and bond anharmonicities in PMMA are determined using compression behaviour of Raman modes. The deduced shock velocity (~3.5 ± 0.4 km/s) in PMMA based on the time evolution of shocked Raman mode at 1.9 GPa is in agreement with the one calculated (~3.7 km/s) from 1‐D radiation hydrodynamic simulations. A comparative study on shock experiment and static high pressure Raman spectroscopic measurements is done. Static pressure measurement up to ~16 GPa show rapid blue shifting of C–H stretching modes.
Artificial soil aeration increases soil bacterial diversity and tomato root performance under greenhouse conditions
Authors: Li Yuan , Niu Wenquan , Zhang Mingzhi , Wang Jingwei , Zhang Zhenxing
Published: January 2020

Soil aeration can enhance soil enzyme activity and plant growth. These effects may be caused by variations in soil microbial diversity and plant root development. However, little is known about the responses of soil microbial composition, structure, and diversity and plant root development to artificial soil aeration. The aims of this study were to examine the composition, structure, and diversity of rhizosphere bacterial communities and tomato root morphology under four aeration volumes in combination with drip‐tubing placed at two different soil depths. The aeration volumes (V) were 0, 0.5, 1, and 1.5 times (CK, V1, V2, and V3, respectively) the standard aeration volume. The drip irrigation tube burial depths were 15 (D15) and 40 cm (D40). The results demonstrated that soil aeration had a significant influence on root performance (root morphology and activity) and soil bacterial diversity in the tomato root zone. In comparison with the CK treatment, V3 soil aeration increased root length, surface area, tip number, and activity by 7.9%, 6.3%, 14.5%, and 7.0%, respectively. The abundance‐based coverage estimator, Chao index, and Shannon diversity increased by 5.3%, 4.7%, and 3.5%, respectively. The abundance of Acidobacteria increased and that of Gammaproteobacteria decreased in response to the soil aeration treatments; conversely, Geobacteraceae and Halanaerobiaceae were eliminated. Moreover, different subsurface tubing placement depths changed the rhizosphere bacterial community. The results indicate that soil aeration ameliorates hypoxic conditions and provides benefits to soil bacterial communities and root morphology.
Synthesis, characterisation, and tribological evaluation of Mn3B7O13Cl nanoparticle as efficient antiwear lubricant in the sliding wear between tantalum strips and steel ball
Authors: Xiong Sang , Liang Dong , Wu Hao , Zhang Baosen
Published: January 2020

The Mn3B7O13Cl nanoparticle (~30 nm) has been prepared by sol‐gel method and characterised by powder X‐ray diffraction (XRD) and transmission electron microscopy (TEM). The tribological properties of prepared Mn3B7O13Cl nanoparticle and the common nano‐Cu and nano‐Fe nanoparticles as antiwear additives with various concentrations in polyalphaolefin (PAO) base oil have been investigated. PB values of nano‐Mn3B7O13Cl added oil are superior to base oil, nano‐Cu and nano‐Fe added oil with the same content, and it reaches the value of 637 N. The wear scar diameter is 0.52 mm when the concentration is only 0.2 wt.%. And meanwhile, Mn3B7O13Cl nanoparticle as efficient antiwear lubricant and commercial oil was measured in the sliding wear between tantalum strip and 52100 bearing steel ball by MFT‐3000 friction and wear tester at an optimised additive concentration (0.2 wt.%). Coefficient of friction of tantalum strips is reduced by 41.5% compared with that of the commercial oil. Surface morphology studies and X‐ray photoelectron spectroscopy (XPS) analysis have revealed that the prominent tribological behaviour of Mn3B7O13Cl was caused by the formation of ~ 30‐nm tribofilm made of adsorbed boron and tribosintered nano‐Mn3B7O13Cl. Therefore, Mn3B7O13Cl nanoparticle has a potential to develop as friction‐reducing and antiwear lubricant in the sliding wear between tantalum strips and steel ball to avoid the severe wear.
An Efficient Thermal Elimination Pathway toward Phosphodiester Hydrogels via a Precursor Approach
Authors: Dera Rafael , Diliën Hanne , Adriaensens Peter , Guedens Wanda , Cleij Thomas J.
Published: January 2020

Phosphodiester hydrogels offer a wide range of fascinating properties. Not only do they exhibit excellent hemocompatibility and cellular compatibility, they also show a remarkable resistance to protein adsorption, thereby limiting the foreign body response. In this work, phosphodiester‐crosslinked hydrogels are produced by a simple free‐radical polymerization of a phosphotriester crosslinker. In a second step, this material is transformed to the phosphodiester, by heating it up to 60 °C in phosphate‐buffered saline. Compared to earlier methods, there is no need for acids, bases, or oxidizing agents to achieve this final conversion to the phosphodiester. This method thus reduces the risk to damage or degrade any sensitive biomolecules that might be of interest to tissue engineers, such as various growth factors or other proteins. The phosphotriester crosslinker is readily synthesized out of common laboratory chemicals in multigram quantities with good yield and easy workup and purification.
Inkjet Printing of Curing Agent on Thin PDMS for Local Tailoring of Mechanical Properties
Authors: Naserifar Naser , Yerneni Saigopalakrishna S. , Weiss Lee E. , Fedder Gary K.
Published: January 2020

Rapid prototyping of thin, stretchable substrates with engineered stiffness gradients at desired locations has potential impact in the robustness of skin‐wearable electronics, as the gradients can inhibit cracking of interconnect and delamination of embedded electronic chips. Drop‐on‐demand inkjetting of thinned polydimethylsiloxane (PDMS) curing agent onto a spin‐cast 80 µm‐thick 20:1 (base: curing agent) PDMS substrate sets the elastic modulus of the subsequently cured film with sub‐millimeter accuracy. The inkjet process creates digitally defined stiffness gradient spans as small as 100 µm for single droplets. Varying the drop density results in differences in elastic modulus of up to 80%. In jetting tests of curing agent into pure base PDMS, a continuous droplet spacing of 100 µm results in smooth lines with total widths of 1 mm and a curing agent gradient span of ≈300 µm. Release of freeform mesh elastomer microstructures by removing the uncured base after selective jetting of curing agent into pure base PDMS results in structural line width resolution down to 500 µm.
Be proactive or inactive: The effects of systematic job riskiness on effort investment
Authors: Yang Fanzheng , Shi Yujiao , Weng Weiwei
Published: January 2020

A company's success heavily relies on its employees' willingness to take initiative at the workplace. With three representative types of risky environments introduced and a series of incentive schemes implemented in the order that mimics the trial process of a company's search for an effective incentive design, we experimentally explore the interplay between systematic job riskiness and managerial practices in determining individuals' risky effort input. Our findings demonstrate that the effectiveness of typical motivational practices, including competitive schemes and the combined use of peer feedback, could vary across risky working environments systematically.
Managerial style in cost asymmetry and shareholder value
Authors: Lopatta Kerstin , Kaspereit Thomas , Gastone Laura‐Maria
Published: January 2020

We show that CEOs' contribution to SG&A cost asymmetry is associated with lower shareholder value. CEO‐related excess SG&A cost stickiness of CEOs with compensation less tied to shareholder value creation and high power drive this association. Last, we provide first evidence that cost asymmetry incorporates a harmful element to the firm and shareholders, namely CEO‐related excess SG&A cost asymmetry.
Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type
Authors: Faber Jennifer , Giordano Ilaria , Jiang Xueyan , Kindler Christine , Spottke Annika , Acosta‐Cabronero Julio , Nestor Peter J. , Machts Judith , Düzel Emrah , Vielhaber Stefan , Speck Oliver , Dudesek Ales , Kamm Christoph , Scheef Lukas , Klockgether Thomas
Published: January 2020

Background

Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA‐C) and sporadic adult‐onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA‐C when compared with SAOA.

Objectives

The objective of this study was to identify structural differences of brain gray and white matter between both patient groups.

Methods

We used magnetic resonance imaging to acquire T1‐weighted images and diffusion tensor images from 12 MSA‐C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel‐based‐morphometry, tract‐based spatial statistics, and tractography‐based regional diffusion tensor images analysis.

Results

Whole‐brain and cerebellar‐focused voxel‐based‐morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA‐C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA‐C patients. The tract‐based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA‐C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography‐based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA‐C, but not SAOA.

Conclusion

Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA‐C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA‐C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Cardiac arrest in a mother and daughter and the identification of a novel RYR2 variant, predisposing to low penetrant catecholaminergic polymorphic ventricular tachycardia in a four‐generation Canadian family
Authors: Tung Matthew , Van Petegem Filip , Lauson Samantha , Collier Ashley , Hodgkinson Kathy , Fernandez Bridget , Connors Sean , Leather Rick , Sanatani Shubhayan , Arbour Laura
Published: January 2020

Background

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia syndrome characterized by adrenergically driven ventricular arrhythmia predominantly caused by pathogenic variants in the cardiac ryanodine receptor (RyR2). We describe a novel variant associated with cardiac arrest in a mother and daughter.

Methods

Initial sequencing of the RYR2 gene identified a novel variant (c.527G > T, p.R176L) in the index case (the mother), and her daughter. Structural analysis demonstrated the variant was located within the N‐terminal domain of RyR2, likely leading to a gain‐of‐function effect facilitating enhanced calcium ion release. Four generation cascade genetic and clinical screening was carried out.

Results

Thirty‐eight p.R176L variant carriers were identified of 94 family members with genetic testing, and 108 family members had clinical evaluations. Twelve carriers were symptomatic with previous syncope and 2 additional survivors of cardiac arrest were identified. Thirty‐two had clinical features suggestive of CPVT. Of 52 noncarriers, 11 had experienced previous syncope with none exhibiting any clinical features of CPVT. A documented arrhythmic event rate of 2.89/1000 person‐years across all carriers was calculated.

Conclusion

The substantial variability in phenotype and the lower than previously reported penetrance is illustrative of the importance of exploring family variants beyond first‐degree relatives.