bluuebunny/crossref_metadata_2025 huggingface dataset:
BPI19-011: Assessment and Management of Older Patients With Metastatic Breast Cancer (MBC) Among Community Oncologists in the United States
Authors: Dotan Efrat , Handorf Elizabeth , Meeker Caitlin R. , Lewis Bianca , Filchner Kelly , Winn Jennifer S. , Goldstein Lori J.
Published: March 2019

Introduction: Geriatric assessment (GA) is recommended for evaluating an older cancer patient’s fitness for treatment; however, it is underutilized in the community. We sought to define the gaps that exist in community oncology practices in the assessment and management of older MBC patients through implementation and training on the use of GA for the care of older MBC patients. Methods: The first phase evaluated community oncology providers using questionnaires regarding their assessment and management of older MBC patients. The second phase included training through implementation of a patient self-administered GA among patients ≥65-years-old with MBC. The providers were blinded to the results of the GA and provided their assessment. Comparison of the 2 evaluations was conducted. The GA was ultimately shared with the providers, who were questioned about the effect of the results on care recommendations. Results: 43 providers from 10 practices were enrolled. Phase I revealed the majority (77%) of providers recognized the utility of GA, yet only 42% routinely conducted a GA pretreatment. Most providers (77%) reported evaluating various GA domains through patient interview rather than validated assessments. Validated scales were used in low rates to evaluate cognition (23%), psychosocial status (12%), and toxicity risk (9%). The limited use of validated assessment tools was not influenced by the provider’s demographics or their views of GA utility. Eighty patients took part in the training phase of the study to date, with average age 74 (range, 65–90) and 84% Caucasian. The majority of patients had subtype ER/PR+, HER2- (75%) and 46% were on first-line therapy. 277 recommended interventions were identified: 174 immediate interventions and 103 suggested interventions. Following review of these results, providers reported being surprised in 40% of the cases, mainly with lower than expected cognitive or social support scores. The providers reported plans for change in management in 44% of the patients as a result of the GA findings. Conclusion: Despite acknowledgement of the value associated with pretreatment GA, it is rarely used in the community. Furthermore, interview rather than validated assessment tools are used to identify age-related concerns. In our preliminary results, the GA identified a large number of deficient areas that had not been identified through the provider’s assessment, and resulted in management change. Additional updated results will be presented at the conference.
HSR19-111: Disparities in Guideline-Concordant Care Among HER2 Positive Metastatic Breast Cancer Patients
Authors: Vyas Ami M. , Aroke Hilary , Kogut Stephen J.
Published: March 2019

Background: We examined guideline-concordant care among women with HER2+ MBC and determined the magnitude of differences in guideline-concordant care between those with positive and negative hormone receptor (HR) status by utilizing a non-linear decomposition technique. Methods: We conducted a retrospective observational cohort study using the Surveillance, Epidemiology, End Results-Medicare linked database. The study cohort consisted of women age >66 years diagnosed with HER2+ MBC in 2010–2013 (N=241). Guideline-concordant initial care within 6 months of cancer diagnosis was defined as per NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). A multivariate logistic regression was performed to identify the significant predictors of guideline-concordant care. A post-regression non-linear decomposition was conducted to examine the magnitude of disparities in guideline concordant care by women’s HR status. Results: 76.8% of the study cohort received guideline-concordant care, while 23.2% did not. As compared to those who did not receive guideline-concordant care, women who received guideline-concordant care were significantly more likely to have positive HR status (adjusted odds ratio (AOR)=2.11; P=.04), had good performance status (AOR=3.46; P=.0008), and had a higher number of oncology visits (AOR=8.05; P<.0001). With 1 year increase in age at cancer diagnosis, there was 5% lesser likelihood of receiving guideline-concordant care (AOR=0.95; P=.04). From the decomposition analysis, 19.0% of the disparity in guideline-concordant care between women with positive and negative HR status was explained by differences in their characteristics. Enabling characteristics (marital status, census-level income, and education) explained the highest (22.8%) proportion of the disparity, followed by external environmental factors (location of residence, SEER region, hospitals offering oncology services) at 5.3%, and need-related factors (tumor grade, comorbidity, performance status, number of metastases) at 3.2%. Conclusion: Almost one quarter of the study cohort did not receive guideline-concordant care. There are opportunities to improve cancer care for women with negative HR status who have lower socioeconomic status. The high unexplained portion of differences in guideline-concordant care (81.0%) can be due to patient preferences for treatment, propensity to seek care, and organizational and physician-level factors not captured in the database.
HSR19-082: Epidemiological Findings and Outcomes in Non-Small Cell Lung Cancer Patients with Exon 20 Insertion Mutations: A Meta-Analysis
Authors: Crossland Victoria , Galaznik Aaron , Lin Huamao M. , Tomaras Dimitrios , Garib Shan Ashton , Li Shuanglian , Huang Hui , Forsythe Anna
Published: March 2019

Background: Epidermal growth factor receptor (EGFR) mutations are frequently found in non-small cell lung cancer (NSCLC) patients. Various EGFR mutations respond differently to EGFR tyrosine kinase inhibitors (TKIs), and several TKIs have been approved for use on common mutations but none have been approved for EGFR exon 20 insertions, indicating a need for targeted therapy for this subpopulation. A systematic literature review (SLR) and meta-analysis were conducted to synthesize epidemiological and outcome data for the uncommon EGFR exon 20 insertion mutation. Methods: An SLR was performed on August 7, 2018 following the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using the Population, Intervention Comparators, Outcomes and Study Design (PICOS) criteria. Studies were identified based on a systematic search using key biomedical literature databases: EMBASE, MEDLINE, and Cochrane. Relevant congress abstracts published between 2015–2018 were also identified. Two independent reviewers screened all citations and full-text articles using PICOS-based criteria; any discrepancies were resolved by a third independent reviewer. Data were extracted into a predefined template for meta-analysis and summarized using the PRISMA flow diagram. Results: A total of 61 studies reporting the number of EGFR mutation−positive patients and/or NSCLC patients were identified. A meta-analysis found that 3.7% of EGFR mutation−positive patients and 0.8% of NSCLC patients harbored the EGFR exon 20 insertion, with geographic variations in epidemiology. There were 12, 10, and 12 studies, respectively, that reported overall survival, progression-free survival, and overall response rates in 2 cohorts, patients with EGFR exon 20 insertions and patients without EGFR exon 20 mutations. A Most patient populations in these studies included a mixture of treatment at various lines. A meta-analysis of outcomes across these studies showed that patients with EGFR exon 20 insertions experienced worse outcomes compared with those without the mutation (Table 1). Meta-analyses were weighted based on each study’s relevant population. No economic or quality of life studies were identified. Conclusions: Exon 20 insertion mutations represent an important subgroup of EGFR mutations in patients with NSCLC, and current therapies have limited efficacy. These relatively poor outcomes indicate a need for novel treatment strategies.
QIM19-128: Improving Oral Chemotherapy Safety in Adult Neuro-Oncology Clinics
Authors: Gershon Megan , Pena Justine , Bains Chamnjot , Salas Sarah , McGranahan Tresa , Nagpal Seema
Published: March 2019

Background: The development of oral chemotherapies (OC) have transformed cancer care for millions of patients. Most patients with brain tumors have temozolomide (TMZ) delivered to their home. While this has improved the patient experience, it presents significant challenges to safety of prescription, administration, and side effect monitoring. While there are guidelines for documentation, there is not a best practices system for managing OC. This project identified areas of latent errors and implemented a standardized process for OC management. Methods: After review of the literature, we developed a process map for our institution’s practice and performed hazard analysis. We then evaluated the process at 3 other neuro-oncology practices. Based on these evaluations, changes were implemented at several stages (Table 1). Objective binary measures that could be recorded for every TMZ prescription were collected by chart review of the 6 months prior to process change. These measures were monitored every 2 weeks after process change implementation using run charts. A baseline process mean was calculated for each measure from the 6 months before program implementation. Successful change implementation was defined as 7 consecutive 2-week averages that were continually on one side of the process mean. Results: At the time of this abstract submission, we had successfully reduced refills for OC and increased documentation of dose calculation and dose ordered. There is improvement in independent dose calculation by 2 providers and dedicated chemotherapy teaching visits; however, these have not yet reached criteria for process change. Additionally, oral chemotherapy order sets were created in the electronic medical records system and an on-site specialty pharmacy was added as another safety measure in OC management. Conclusions: This project used published studies and multi-institutional process mapping and hazard analysis to implement a standardized ordering of TMZ for patients with brain tumors. This process can be implemented for OC management in other oncology practices.
HSR19-099: Harnessing the Voice of Patients With Genetic Mutations in NSCLC Treatment
Authors: May Suepattra G. , Huber Caroline , Silverstein Alison R. , Linthicum Mark , Shafrin Jason , Brown Katie , Roy Upal Basu , Bright Jennifer
Published: March 2019

Background: Targeted therapies for non-small lung cancer (NSCLC) have vastly improved survival and other outcomes for patients whose tumors have genetic mutations such as ALK, BRAF, EGFR, and ROS1. Identification of genetic mutations often indicates a mutation-specific course of therapy; however, the relationship between genetic mutation status, patient treatment preferences, and other determinants of patient value in NSCLC cancer care is not well understood. Methods: Qualitative study utilizing focus groups and in-depth interviews were conducted with metastatic NSCLC patients who had received systemic therapy. Interviews explored how patients valued and prioritized factors and attributes associated with NSCLC therapy. Interviews were audio-recorded, transcribed, and coded for key themes using MAXQDA qualitative data analysis software (VERBI, GmbH). Thematic analysis identified determinants of value that patients with genetic mutations considered most important in decision-making. Results: Of 19 total participants with metastatic NSCLC (mean [SD] age, 55.8 [12.6] years; 79% female), 15 (79%) reported a known genetic mutation. Most participants valued oncogene testing and indicated that they had developed a distinct identity based on their specific mutation. Further, participants in our study with identified mutations reported facing distinctly different decisions than those without known mutations. Participants also highlighted unmet needs for diagnosis, treatment, and support tailored to their patient subgroup, including a critical need for better provider training and awareness of genetic testing and mutation-specific treatment options. Across patient subgroups, mutation-specific social media and support networks were highly valued for the care and treatment information they provide, especially among those with rare mutations, limited treatment options, or less-experienced providers. Conclusions: Our study suggests important differences among NSCLC patients based on identified genetic mutations. As treatment for NSCLC evolves, so do the needs and preferences of patients, especially those with driver mutations. Our findings highlight the need for a better understanding of how mutation status may impact patient goals and preferences in order to provide the highest value care to each patient.
EPR19-069: Opioid Use Among Cancer Patients Undergoing Surgery and Their Associated Risk of Re-admissions and Emergency Department Visits in the 1-Year Postsurgical Period
Authors: Kurteva Siyana , Tamblyn Robyn , Meguerditchian Ari
Published: March 2019

Background: Prescription opioid use and overdose has steadily increased over the past years, resulting in a dramatic increase in opioid-related emergency department (ED) visits and hospitalizations. Methods: This study used a prospective cohort of cancer patients having undergone surgery in Montreal (Quebec) to describe their post-discharge opioid use and identify potential patterns of unplanned health service use (ED visits, hospitalizations). Provincial health administrative claims were used to measure opioid dispensation as well as hospital re-admissions and ED visits. The hospital warehouse, patient chart and patient interview will be used to further describe patient’s medical profile. Marginal structural models will be used to model the association between use of opioids and risk of ED visits and hospitalizations. Inverse probability of treatment and censoring weights will be constructed to properly adjust for confounders that may be unbalanced between the opioid and non–opioid users as well as to account for competing risk due to mortality. Reasons for the re-admissions will also be presented as part of the analyses. Covariates will include patient comorbidities, medication history, and healthcare system characteristics such as nurse-to-patient and attending physician-to-patient ratios. Results (interim): A total of 821 were included in the study; of these, 73% (n=597) were admitted for a cancer procedure. At postoperative discharge, 605 (74%) of patients had at least one opioid dispensation, of which the majority (67%) were oxycodone with hydromorphone being the second most prescribed (28%). Among those who filled a prescription, mean age was 66 (13.4), 68% had no previous history of opioid use, and 10% have had 3 or more dispensing pharmacies in the year prior to admission, compared to less than 1% for the non–opioid users. Overall, 343 people refilled their opioid prescription at least once and 128 at least twice during the 1-year postoperative period. Among cancer patients who were opioid users, 214 ED visits occurred in the 1 year after surgery compared to only 40 for the non-cancer opioid users. Conclusion: This study will help to identify the risk profile of cancer patients who are most likely to continue using opioids for prolonged periods following surgical procedures as well as quantify the impact of opioid use and its associated burden on the healthcare system in order to identify areas for possible interventions.
BPI19-015: Reduction of Inappropriate Prophylactic Pegylated Granulocyte Colony-Stimulating Factor (pGCSF) Use for Lung Cancer Patients: Five-Year Follow Up of a Quality Improvement (QI) Initiative at the Cleveland Clinic Taussig Cancer Institute (TCI)
Authors: Hubben Anne K. , Pennell Nathan , Shapiro Marc , Savage Craig , Stevenson James P.
Published: March 2019

Purpose: National guidelines do not include routine pGCSF as primary prophylaxis (PP) for patients receiving chemotherapy associated with a low risk for febrile neutropenia (FN). Inappropriate pGCSF can increase patient morbidity, financial burden, and overall health care costs. In 2013, an interdisciplinary group at TCI implemented a QI project to reduce inappropriate PP pGCSF in patients with lung cancer; this included prescriber education and modification of chemotherapy orders by risk of FN in the electronic medical record (EMR). Inappropriate pGCSF was reduced from 28% to 4%. In this 5-year follow up study we analyzed pGCSF use in lung cancer patients. Methods: We conducted a review of lung cancer patients who received pGCSF with chemotherapy initiated between January 2016 and August 2018. PP pGCSF use was appropriate if prescribed with chemotherapy regimens with a high risk (>20%) for FN, or intermediate risk (10%–20%) if other accepted FN risk factors were present. PP use with FN low-risk (<10%) chemotherapy was considered inappropriate. Treating physicians were anonymously surveyed about their practices. Results: 294 patients with lung cancer received 1,353 doses of pGCSF during the study period. 58 (20%) were treated at TCI by subspecialty thoracic oncologists and 236 (80%) were treated at regional network sites. 100/294 (34%) patients received low-risk regimens. 62/100 (62%) patients treated with low-risk regimens received 311 doses of PP pGCSF (inappropriate use). 5/62 (8%) of inappropriate use occurred at TCI; 57/62 (92%) at network sites. Of 130 patients who received an intermediate risk regimen, 99 (76%) received PP pGCSF. At least one risk factor for FN was identified in 80/99 (80%) of these patients; age >65 and prior chemotherapy or radiation were the top-cited factors. 33/294 (11%) patients were hospitalized for FN during the study period; 7/100 (7%) received low-risk regimens, 15/130 (11.5%) intermediate-risk, and 11/46 (24%) high-risk regimens. All physicians responding to the survey indicated awareness of guidelines and EMR risk identification. Conclusion: After initial success at our center, we found that guideline-based alignment of pGCSF prescribing in lung cancer patients was not sustained. Despite reported familiarity with guidelines for PP pGCSF use, this analysis suggests an opportunity for re-education and further EMR modification. Based on July 2018 CMS average sales price, reduction in inappropriate use presents a potential cost savings of $1.5 million during the study.
Pherekydes von Athen: Struktur der Historiai (oder: Der längere Weg von Athen bis Alexandria)
Authors: Pàmias Jordi
Published: March 2019

The original structure of Pherekydes’ mythographical collection remains a controversial issue. Its rearrangement in the Hellenistic period did not merely consist of a new division of the books by taking the length of the rolls into account. The article attempts to show that the overall structure of the Historiai underwent a major revision in the library of Alexandria. The author advances the theory that Pherekydes’ work wasreorganized into an encyclopaedia of historiai arranged alphabetically.
Criticism and Rework of Homeric Narrative in Dio's Trojan Discourse
Authors: Scafoglio Giampiero
Published: March 2019

Dio Chrysostom, in his Trojan Discourse (Speech 11) rewrites the story of the Trojan War in a new and different way (with Trojans’ victory over Greeks, the murder of Hector by Achilles, and so on), in contrast with the tale of the Iliad and under the pretense of an historical reconstruction. He preys on Homeric narrative techniques (such as the selective and motivated plot of the Iliad, and the first-person tale in the Odyssey), in order to disprove the traditional version of the legend and to pave the way for a new view. Dio takes a metaliterary and intertextual approach to Homeric epics, insofar as he criticizes and deconstructs their narratives (bearing in mind Homeric criticism by Aristotle and by Alexandrine grammarians), in order to rebuild the story anew. He also provides a specimen of generic crossing, since he frames an epic subject in the context of a prose speech that belongs to epidictic oratory and that simulates some historiographical practices.
Penser les carnets numériques d’écrivain : écritures médiatisées et réinvestissement de l’idée de publication
Authors: Audet René
Published: March 2019

Envisageant la possibilité d’une transposition de la pratique du carnet d’écrivain en contexte numérique, cet article examine les enjeux du support sur les écritures littéraires telles qu’elles apparaissent dans des blogues et des sites d’écrivains. La réévaluation du rôle joué par la publication (autonome et médiée) des textes sur le statut d’écrivain et sur leur lectorat conduit à définir la fonction d’implémentation des oeuvres (notion empruntée à Nelson Goodman) comme une clé interprétative de la publication numérique.
La crisi planetària de l’antropocè: Evolució cultural i canvi ambiental
Authors: Terradas Jaume
Published: March 2019

Vivim una crisi que anomenem antropocè. La força determinant d’aquest període és l’expansió humana per un procés biològic nou, l’evolució cultural, que ens permet una construcció de nínxol d’enorme amplitud, gràcies sobretot a l’increment de l’ús d’energia exosomàtica. L’acceleració és fortíssima i els efectes sobre el complex socioecològic són imprevisibles. El canvi ambiental genera noves pressions selectives sobre les societats humanes que miren d’adaptar-s’hi forçant nous canvis. Creixement demogràfic i millora de condicions de vida amenacen recursos i processos bàsics de suport a la vida. N’estudiem els efectes ecològics, però les causes són socials. La destrucció de biodiversitat i cultures és l’herència del colonialisme que segueix per altres vies o que protagonitzen altres actors. Necessitem missatges universals, no pretendre perpetuar la supremacia occidental i la ideologia de progrés indefinit, sinó un esforç intercultural per consensuar valors universals i generar institucions que s’hi corresponguin.
Humans 2.0: Writing the future of human evolution
Authors: Marfany Gemma
Published: March 2019

Can humans control the future evolution of our species? Based on current knowledge in genetics, one can infer and extrapolate what may happen in the near future. After all, if we are to predict the future, we must first understand the foundations of our present. To answer the first question, I will briefly present what we know about our genome and whether we have enough data to infer who we are (known as the genotype–phenotype correlation), then I will present new technological advances and their potential impact on our evolution.
A pobreza infantil e rendimento social de inserção em Portugal: o mesmo problema, tendências distintas
Authors: Diogo Fernando
Published: March 2019

Este artigo centra-se na constatação de que a proporção de crianças (0-17 anos) entre os beneficiários do Rendimento Social de Inserção (RSI) está a descer consistentemente desde há alguns anos, em contraste com uma taxa de pobreza infantil persistentemente alta. Esta contradição é demonstrada através da exploração dos dados sobre o RSI cruzados com as estatísticas do INE referentes à pobreza infantil (ICOR-EU-SILC), medida com base na pobreza monetária. É desenvolvida uma hipótese para explicar esta contradição, assente nas transformações legais do RSI e na dificuldade do estado em desenvolver medidas de apoio social com impacto na pobreza infantil.
Trayectorias y actitudes generacionales: temporalidades y actitudes ante la educación, el trabajo y el consumo de tres generaciones de jóvenes españoles y portugueses
Authors: Vázquez José Duran , Duque Eduardo
Published: March 2019

Este trabajo se propone analizar las trayectorias biográficas de tres generaciones de jóvenes españoles y portugueses (1935-1945, 1955-1965 y 1975-1985) en relación con sus actitudes hacia el mundo de la educación, el trabajo y el consumo. Para la realización de esta investigación, se han empleado como fuentes los distintos Informes de Juventud publicados regularmente desde 1960. Los resultados obtenidos permiten llegar a las siguientes conclusiones: la generación de 1935-45, ha sido la más influenciada por la ética del trabajo; la de 1955-1965 es la primera que participa de los valores de los tres ámbitos analizados; la juventud del periodo 1975-85, es la más socializada en los valores del consumo, valores que ejercerán una mayor influencia sobre los otros dos ámbitos, el educativo y el laboral.
The cryo-EM structure of a 12-subunit variant of RNA polymerase I reveals dissociation of the A49-A34.5 heterodimer and rearrangement of subunit A12.2
Authors: Tafur Lucas , Sadian Yashar , Hanske Jonas , Wetzel Rene , Weis Felix , Müller Christoph W
Published: March 2019

RNA polymerase (Pol) I is a 14-subunit enzyme that solely transcribes pre-ribosomal RNA. Cryo-electron microscopy (EM) structures of Pol I initiation and elongation complexes have given first insights into the molecular mechanisms of Pol I transcription. Here, we present cryo-EM structures of yeast Pol I elongation complexes (ECs) bound to the nucleotide analog GMPCPP at 3.2 to 3.4 Å resolution that provide additional insight into the functional interplay between the Pol I-specific transcription-like factors A49-A34.5 and A12.2. Strikingly, most of the nucleotide-bound ECs lack the A49-A34.5 heterodimer and adopt a Pol II-like conformation, in which the A12.2 C-terminal domain is bound in a previously unobserved position at the A135 surface. Our structural and biochemical data suggest a mechanism where reversible binding of the A49-A34.5 heterodimer could contribute to the regulation of Pol I transcription initiation and elongation.
Abundance of Whales in West and East Greenland in Summer 2015
Authors: Hansen Rikke Guldborg , Boye Tenna K. , Larsen Rasmus S. , Nielsen Nynne H. , Tervo Outi , Nielsen Rasmus D. , Rasmussen Marianne H. , Sinding Mikkel H. S. , Heide-Jørgensen Mads Peter
Published: March 2019

An aerial line transect survey of whales in West and East Greenland was conducted in August-September 2015. The survey covered the area between the coast of West Greenland and offshore (up to 100 km) to the shelf break and in East Greenland from the coast up to 50 km offshore crossing the shelf break. A total of 423 sightings of 12 cetacean species were obtained and abundance estimates were developed for common minke whale, (Balaenoptera acutorostrata), fin whale (Balaenoptera physalus), humpback whale (Megaptera novaeangliae), harbour porpoise (Phocoena phocoena), long-finned pilot whale, (Globicephala melas) and white-beaked dolphin (Lagenorhynchus albirostri). The estimates were corrected for perception bias and availability bias where possible. Data on surface corrections for minke whales and harbour porpoises were collected from whales instrumented with satellite-linked time-depth-recorders. Options for estimation methods are presented and the preferred estimates are: minke whales: 5,095 (95% CI: 2,171-11,961) in West Greenland and 2,762 (95% CI: 1,160-6,574) in East Greenland, fin whales: 2,215 (95% CI: 1,017-4,823) in West Greenland and 6,440 (95% CI: 3,901-10,632) in East Greenland, humpback whales: 993 (95% CI: 434-2,272) in West Greenland and 4,223 (95% CI: 1,845-9,666) in East Greenland, harbour porpoises: 83,321 (95% CI: 43,377-160,047) in West Greenland and 1,642 (95% CI: 319-8,464) in East Greenland, pilot whales: 9,190 (95% CI: 3,635-23,234) in West Greenland and 258 (95% CI: 50-1,354) in East Greenland, white-beaked dolphins 15,261 (95% CI: 7,048-33,046) in West Greenland and 11,889 (95% CI: 4,710-30,008) in East Greenland. The abundance of cetaceans in coastal areas of East Greenland has not been estimated before, but the limited historical information indicates that the achieved abundance estimates were remarkably high. Comparing the estimates from 2015 in West Greenland with a similar survey conducted in 2007, there is a trend towards lower densities in 2015 for the baleen whale species and white-beaked dolphins. Harbour porpoises and pilot whales, however, did not show a similar decline. The decline in baleen whale and white-beaked dolphin abundance is likely due to emigration to the East Greenland shelf areas where recent climate driven changes in pelagic productivity may have accelerated favourable conditions for these species.
Robust and automatic definition of microbiome states
Authors: García-Jiménez Beatriz , Wilkinson Mark D.
Published: March 2019

Analysis of microbiome dynamics would allow elucidation of patterns within microbial community evolution under a variety of biologically or economically important circumstances; however, this is currently hampered in part by the lack of rigorous, formal, yet generally-applicable approaches to discerning distinct configurations of complex microbial populations. Clustering approaches to define microbiome “community state-types” at a population-scale are widely used, though not yet standardized. Similarly, distinct variations within a state-type are well documented, but there is no rigorous approach to discriminating these more subtle variations in community structure. Finally, intra-individual variations with even fewer differences will likely be found in, for example, longitudinal data, and will correlate with important features such as sickness versus health. We propose an automated, generic, objective, domain-independent, and internally-validating procedure to define statistically distinct microbiome states within datasets containing any degree of phylotypic diversity. Robustness of state identification is objectively established by a combination of diverse techniques for stable cluster verification. To demonstrate the efficacy of our approach in detecting discreet states even in datasets containing highly similar bacterial communities, and to demonstrate the broad applicability of our method, we reuse eight distinct longitudinal microbiome datasets from a variety of ecological niches and species. We also demonstrate our algorithm’s flexibility by providing it distinct taxa subsets as clustering input, demonstrating that it operates on filtered or unfiltered data, and at a range of different taxonomic levels. The final output is a set of robustly defined states which can then be used as general biomarkers for a wide variety of downstream purposes such as association with disease, monitoring response to intervention, or identifying optimally performant populations.
Effectiveness of Alternative Control Methods for Tithonia diversifolia on Water Yam (Dioscorea alata) Plot
Authors: Olabode O. S. , Ogunsola A. , Oladapo O. S. , Sangodele A. O.
Published: March 2019

Tithonia diversifolia has become a significant agronomic problem to optimum arable crop production in Nigeria which has necessitated effective and timely control if the good yield is expected on infested soil. This study compared the performance of water yam under different weed control methods on Tithonia infested plot at Ogunba village near Baaya-Oje in Surulere Local Government area of Ogbomoso, Oyo State during the 2015 growing season. Eight (8) control treatments were evaluated namely: Weed control with Atrazine, Diuron, 2 hoe weeding, 3 hoe weeding, Black plastic mulch, grass mulch, Diuron + Atrazine + Plastic mulch (IWM) and unweeded plot. The three (3) hoe weeding and the unweeded plot served as the control treatments. The experiment was laid out in a Randomized complete block design with three replicates. Yam setts were planted at a spacing of    1 m x 1 m to give a population of 10000 plants/ha. Atrazine and Diuron were applied at the rate of 2.5 kg a.i/ha, 2 hoe weeding was done at 3 and 6 weeks after planting (WAP), 3 hoe weeding was done at 3,6 and 9 WAP, while grass mulch was applied at the rate of 5 tons/ha. In IWM, Atrazine and Diuron were applied each at the half recommended rate (1.25 kg/ha) before applying plastic mulch. The treatments were applied pre-emergently on a rain wetted soil after planting. Data were collected on growth and yield parameters of yam as well as on Tithonia weed population and dry matter yield. Results showed that weed control methods significantly (P < 0.05) influenced water yam yield. The highest tuber yield (21 tons/ha) in plastic mulch was comparable to IWM (20 tons/ha), 3 hoe weeding (19 tons/ha) and 2 hoe weeding (18 tons/ha). Grass mulch (16 tons/ha), Diuron (15 tons/ha), Atrazine (14 tons/ha) were also not significantly (P > 0.05) different. Thus, it may be concluded that plastic much is the most efficient of the methods for weed control in yam. The implication of this finding is discussed.
Role of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in the Bone Regeneration: A Systematic Review from 2007-2018
Authors: Dilogo Ismail Hadisoebroto , Fiolin Jessica
Published: March 2019

Background: The therapeutic value of mesenchymal stem cells (MSCs) in tissue engineering and regenerative medicine is attributable in part to paracrine pathways triggered by several secreted factors secreted into culture media. The secreted factor here is known as the conditioned medium (CM) or secretome.

Objectives: This review is aimed to investigate and summarise the in-vitro, pre-clinical in-vivo studies regarding the role of CM-MSC in bone regeneration from 2007 until 2018

Data Sources: A systematic literature search on PubMed, MEDLINE, OVID, Scopus and Cochrane library was carried out by using search terms: Secretome, conditioned medium, mesenchymal stem cell, bone healing, osteogenic, osteogenesis.

Methods: A total of 611 articles were reviewed. Ten articles were identified as relevant for this systematic literature review.

Results: Three tables of studies were constructed for in vitro studies and in-vivo studies.

Conclusion: All of the included in-vitro studies and in-vivo studies have shown a promoting effect of bone regeneration at various stages. Although there are no clinical studies regarding the use of CM-MSC in the human bone regeneration that have been conducted, transplantation of secretome has shown a promising result in the acceleration of bone healing process.
A Review on Abiotic Stress Caused by Industrial Effluents on Seed Quality
Authors: Venudevan B. , Srimathi P. , Begum M. Ameer Junaithal
Published: March 2019

India is one of the top ten industrialized countries of global importance. But industries release waste products, which exert negative influences by causing toxicity to biotic organisms and environment. Liquid wastes of industries termed as effluents are characterized with possession of organic and inorganic compounds that evolve with varying levels of toxicity based on the type of industry and its bi-product. Recycling of treated effluent serves as an alternative to tie over water scarcity in sustainable agriculture. On the other hand, dilutions of industrial effluents serves as growth stimulants at an optimal concentration and influences the seed and seedling quality characters and aids in improving the productivity of crops. The safe levels of dilutions expressing the seed invigourative effect are reviewed hereunder, which could serve as a solution for disposal of effluent in agriculture in an effective manner.
Rooting of Herbaceous and Semihardwood Cuttings of Guava cv. Século XXI, under Varying Concentrations of Indolebutyric Acid
Authors: Da Costa Jussara Cristina Firmino , Mendonça Rejane Maria Nunes , Da Silva Gerciane Cabral , Silva Silvanda de Melo , Pereira Walter Esfrain , Dos Santos Carlos Eduardo Magalhães
Published: March 2019

In the commercial production of guava seedlings (Psidium guajava L.) the quality of the cuttings, homogeneity, high percentage of rooting are the factors important to be analyzed. Therefore, as the Século XXI cultivar is recent, it is necessary to do more studies regarding the behavior of this guava to the factors that aid in the rhizogenic process. The objective of this work was to verify the concentrations of indolebutyric acid (IBA) that provide the best rooting of cuttings herbaceous and semihardwood, as well as to verify the best kind of cuttings used for vegetative propagation the guava cuttings cultivar ‘Século XXI’. The experimental design was completely randomized in a 5 x 2 + 1 factorial design, beginning with five concentrations of IBA (0, 1000, 1500, 2000 and 2500 mg L-1), two kinds of cuttings (herbaceous and semihardwood) and one control treatment (immersed in distilled water for 12 hours), with four replications and 10 cuttings per plot. In relation of the variables: the percentage of cuttings live without roots, callus, number of roots and dry weight of shoots did not present significant interaction among treatments, not adjusting to any regression model. Therefore, concluding that the herbaceous cutting is the most indicated for the propagation of guava seedlings of ‘Século XXI’; The concentration of 2500 mg L-1 of IBA promotes a higher percentage of rooted semihardwood cuttings without leaf; The hormone solution diluted with alcohol 50% (v/v) resulted in toxicity for herbaceous and semihardwood cuttings cv. Século XXI.
Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinoma
Authors: Yu Namhee , Yong Seunghui , Kim Hong Kwan , Choi Yoon‐La , Jung Yeonjoo , Kim Doyeon , Seo Jihae , Lee Ye Eun , Baek Daehyun , Lee Jinseon , Lee Seungjae , Lee Jong Eun , Kim Jaesang , Kim Jhingook , Lee Sanghyuk
Published: March 2019

The roles of miRNAs in lung cancer have not yet been explored systematically at the genome scale despite their important regulatory functions. Here, we report an integrative analysis of miRNA and mRNA sequencing data for matched tumor–normal samples from 109 Korean female patients with non‐small‐cell lung adenocarcinoma (LUAD). We produced miRNA sequencing (miRNA‐Seq) and RNA‐Seq data for 48 patients and RNA‐Seq data for 61 additional patients. Subsequent differential expression analysis with stringent criteria yielded 44 miRNAs and 2322 genes. Integrative gene set analysis of the differentially expressed miRNAs and genes using miRNA–target information revealed several regulatory processes related to the cell cycle that were targeted by tumor suppressor miRNAs (TSmiR). We performed colony formation assays in A549 and NCI‐H460 cell lines to test the tumor‐suppressive activity of downregulated miRNAs in cancer and identified 7 novel TSmiRs (miR‐144‐5p, miR‐218‐1‐3p, miR‐223‐3p, miR‐27a‐5p, miR‐30a‐3p, miR‐30c‐2‐3p, miR‐338‐5p). Two miRNAs, miR‐30a‐3p and miR‐30c‐2‐3p, showed differential survival characteristics in the Tumor Cancer Genome Atlas (TCGA) LUAD patient cohort indicating their prognostic value. Finally, we identified a network cluster of miRNAs and target genes that could be responsible for cell cycle regulation. Our study not only provides a dataset of miRNA as well as mRNA sequencing from the matched tumor–normal samples, but also reports several novel TSmiRs that could potentially be developed into prognostic biomarkers or therapeutic RNA drugs.
Fiber Reinforced Polymer Nanocomposites for Structural Engineering Applications
Authors: Balasubramaniam Bhuvaneshwari , Sathiyan Govindasamy , Palani Gadyam S. , Iyer Nagesh R. , Gupta Raju Kumar
Published: March 2019

Fiber reinforced polymer (FRP) materials are an important and vibrant structural composite material. FRP comprises of strong and stiff reinforcing fibers embedded in a matrix resin, mainly polymer‐based. A fundamental requirement of engineered structural composites is sufficient strength to support the full superimposed and self‐weight loads. In addition to mechanical properties, structural materials should possess robust physical and in‐service characteristics required to function in aggressive and sometimes hostile environments.

Carbon fiber reinforced polymer (CFRP) composites are increasingly being targeted as replacement of steel and repair materials for concrete structures in civil infrastructure applications. Outstanding performances are noticed when CFRP is used for rehabilitation and strengthening of concrete structures. Further, enhancement of strength and stiffness via simple patching techniques provides additional benefits. Although CFRP composites provide an effective method to strengthen concrete structures, degradation of its performance is unavoidable due to different environmental exposure conditions such as moisture, temperature, and various chemicals atmospheres including chloride, alkaline, and salt water. The greater the degradation of structures, the lower will be their load carrying capacity. Hence, particular focus is on the development of advanced fiber reinforced polymer nanocomposites. This article introduces the effect of FRP nanocompositing and strengthening with epoxies for enhanced durability functions of CFRP in retrofitting/rehabilitation applications.
Regulating Mechanotransduction in Three Dimensions using Sub‐Cellular Scale, Crosslinkable Fibers of Controlled Diameter, Stiffness, and Alignment
Authors: Wang Mingkun , Cui Chunxiao , Ibrahim Mazen Mohamed , Han Biao , Li Qing , Pacifici Maurizio , Lawrence John Todd R. , Han Lin , Han Li‐Hsin
Published: March 2019

The extracellular matrix (ECM) is a complex 3D framework of macromolecules, which regulate cell bioactivity via chemical and physical properties. The ECM's physical properties, including stiffness and physical constraints to cell shape, regulate actomyosin cytoskeleton contractions, which induce signaling cascades influencing gene expression and cell fate. Engineering such bioactivity, a.k.a., mechanotransduction, has been mainly achieved by 2D platforms such as micropatterns. These platforms cause cytoskeletal contractions with apico‐basal polarity and can induce mechanotransduction that is unnatural to most cells in native ECMs. An effective method to engineer mechanotransduction in 3D is needed. This work creates FiberGel, a 3D artificial ECM comprised of sub‐cellular scale fibers. These microfibers can crosslink into defined microstructures with the fibers' diameter, stiffness, and alignment independently tuned. Most importantly, cells are blended amongst the fibers prior to crosslinking, leading to homogeneously cellularized scaffolds. Studies using mesenchymal stem cells showed that the microfibers' diameter, stiffness, and alignment regulate 3D cell shape and the nuclei translocation of transcriptional coactivators YAP/TAZ (yes‐associated protein/transcriptional coactivator), which enables the control of cell differentiation and tissue formation. A novel technology based on repeated stretching and folding is created to synthesize FiberGel. This 3D platform can significantly contribute to mechanotransduction research and applications.
Workplace heat exposure, health protection, and economic impacts: A case study in Canada
Authors: Vanos Jennifer , Vecellio Daniel J. , Kjellstrom Tord
Published: March 2019

Background

Occupational heat exposure is a serious concern for worker health, productivity, and the economy. Few studies in North America assess how on‐site wet bulb globe temperature (WBGT) levels and guidelines are applied in practice.

Methods

We assessed the use of a WBGT sensor for localized summertime heat exposures experienced by outdoor laborers at an industrial worksite in Ontario, Canada during the warm season (May‐October) from 2012 to 2018 inclusive. We further examined informed decision making, approximated workers’ predicted heat strain (sweat loss, core temperature), and estimated potential financial loss (via hourly wages) due to decreased work allowance in the heat.

Results

Significantly higher worksite WBGT levels occured compared with regional levels estimated at the airport, with an upward trend in heat warnings over the 7 years and expansion of warnings into the fall season. The maximum WBGT during warnings related strongly to predicted hourly sweat loss. On average, 22 hours per worker were lost each summer (~1% of annual work hours) as a result of taking breaks or stopping due to heat. This amount of time corresponded to an average individual loss of C$1100 Canadian dollars (~C$220,000 combined for ~200 workers) to workers or the company. The additional losses for an enterprise due to reduced product output were not estimated.

Conclusions

Worksite observations and actions at the microscale are essential for improving the estimates of health and economic costs of extreme heat to enterprises and society. Providing worksite heat metrics to the employees aids in appropriate decision making and health protection.
Biallelic novel missense HHAT variant causes syndromic microcephaly and cerebellar‐vermis hypoplasia
Authors: Abdel‐Salam Ghada M. H. , Mazen Inas , Eid Maha , Ewida Nour , Shaheen Ranad , Alkuraya Fowzan S.
Published: March 2019

We report two siblings with microcephaly, early infantile onset seizures, and cerebellar vermis hypoplasia, in whom whole exome sequencing revealed a novel homozygous missense (c.770T>C, p.[Leu257Pro]) variant in the hedgehog acyl‐transferase gene (HHAT), encoding an enzyme required for the attachment of palmitoyl residues that are critical for multimerization and long and short range hedgehog signaling. There is a report of one family with Nivelon–Nivelon–Mabille syndrome in which HHAT was proposed as the likely candidate gene. The phenotypic overlap with the family we report herein provides further evidence implicating HHAT in cerebellar development and the pathogenesis of this rare spectrum.
Effect of TiO2 on Altering Direction of Interfacial Charge Transfer in a TiO2‐Ag‐MPY‐FePc System by SERS
Authors: Wang Yue , Liu Jing , Ozaki Yukihiro , Xu Zhangrun , Zhao Bing
Published: March 2019

Interfacial charge transfer (CT) is of interest owing to its effect on the performance of molecular photovoltaic (PV) devices. The characteristics and structures of interfacial materials, such as TiO2 nanoparticles (NPs) in some solar cells, are employed to adjust the CT process. In this study, three kinds of interfacial systems, including a solar cell‐like TiO2‐Ag‐ p‐mercaptopyridine (MPY)‐ iron phthalocyanine (FePc) system, are compared to investigate the interfacial CT process using surface‐enhanced Raman scattering (SERS) spectroscopy. The SERS results show the significance of TiO2 NPs in the system on altering the direction and path of the interfacial CT, which is closely associated with the CT enhancement contribution to SERS in such an interfacial system. SERS spectroscopy is expected to be a promising technique for the exploration and estimation of the interfacial CT behavior in PV devices, which may further extend the applications of SERS in the field of solar cells.
Synthesis and characterization of Co (III) salen complex immobilized on cobalt ferrite‐silica nanoparticle and their application in the synthesis of spirooxindoles
Authors: Nasseri Mohammad A. , Hemmat Kaveh , Allahresani Ali
Published: March 2019

The preparation, characterization and catalytic application of Co (III) salen complex loaded on cobalt ferrite‐silica nanoparticle [CoFe2O4@SiO2@ Co (III) salen complex] are described. Co (III) salen complex loaded on ferrite cobalt‐silica nanoparticles is characterized by transmission electron microscopy, scanning electron microscopy coupled with energy‐dispersive X‐ray, vibrating‐sample magnetometer and Fourier transform‐infrared analyses. The thermal stability of the material is also determined by thermal gravimetric analysis. An average crystallite size is determined from the full‐width at half‐maximum of the strongest reflection by using Scherrer's approximation by powder X‐ray diffractometry. The efficiency of CoFe2O4@SiO2@Co (III) salen complex is investigated in the synthesis of spirooxindoles of malononitrile, various isatins with 1,3‐dicarbonyles. The nanocatalyst demonstrated excellent catalytic activity that gave the corresponding coupling products in good to excellent yields. Moreover, the recoverability and reusability of CoFe2O4@SiO2@Co (III) salen complex is investigated where nanocatalyst could be recovered and reused at least five times without any appreciable decrease in activity and selectivity, which confirmed its high efficiency and high stability under the reaction conditions and during recycling stages.