bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety review of hydroxyprogesterone caproate in women with a history of spontaneous preterm birth
Authors: Sibai Baha , Saade George R. , Das Anita F. , Gudeman Jennifer 
Published: October 2020

Abstract17-alpha-hydroxyprogesterone caproate (17P) has been in use for prevention of recurrent preterm birth since 2003 when the Meis trial was published. A requirement for Food and Drug Administration approval of 17P was a confirmatory trial, called “PROLONG”, which was recently completed, but did not replicate the efficacy demonstrated in the Meis trial. This review analyzes the safety data from each trial, as well as integrated data from the two trials. The relative risks (95% CI) with 17P versus placebo in the integrated dataset were 0.66 (0.25–1.78) for miscarriage, 1.83 (0.68–4.91) for stillbirth, and 0.86 (0.53–1.41) for all fetal and neonatal death. The rate of gestational diabetes in the integrated dataset was 3.6% for 17P vs. 3.8% for placebo. Similar findings with low and comparable rates between 17P and placebo were also found for other adverse events. The integrated safety data demonstrate a favorable safety profile that was comparable to placebo.
A multistate model of survival prediction and event monitoring in prefibrotic myelofibrosis
Authors: Carobbio Alessandra , Guglielmelli Paola , Rumi Elisa , Cavalloni Chiara , De Stefano Valerio , Betti Silvia , Rambaldi Alessandro , Finazzi Maria Chiara , Thiele Juergen , Vannucchi Alessandro M. , Tefferi Ayalew , Barbui Tiziano 
Published: October 2020

AbstractAmong 382 patients with WHO-defined prefibrotic myelofibrosis (pre-PMF) followed for a median of 6.9 years, fibrotic or leukemic transformation or death accounts for 15, 7, and 27% of cases, respectively. A multistate model was applied to analyze survival data taking into account intermediate states that are part of the clinical course of pre-PMF, including overt PMF and acute myeloid leukemia (AML). Within this multistate framework, multivariable models disclosed older age (>65 years) and leukocytosis (>15 × 109/L) as predictors of death and leukemic transformation. The risk factors for fibrotic progression included anemia and grade 1 bone marrow fibrosis. The outcome was further affected by high molecular risk (HMR) but not driver mutations. Direct transition to overt PMF, AML, or death occurred in 15.2, 4.7, and 17.3% of patients, respectively. The risk of AML was the highest in the first 5 years (7%), but leveled off thereafter. Conversely, the probability of death from overt PMF or AML increased more rapidly over time, especially when compared to death in the pre-PMF state without disease progression. The probability of being alive with pre-PMF status decreased to 70 and 30% at 10 and 20 years, respectively. This study highlights the aspects of the clinical course and estimates of disease progression in pre-PMF.
The quality of life index: a pilot study integrating treatment efficacy and quality of life in oncology
Authors: Basu A. , Philip E. J. , Dewitt B. , Hanmer J. , Chattopadhyay A. , Yau C. , Melisko M. E. , Esserman L. J. 
Published: October 2020

AbstractThe majority of women diagnosed with breast cancer will experience some form of drug-related toxicity and subsequent impairments in Health-related Quality of Life (HRQoL). Despite this, HRQoL is assessed inconsistently and there is no validated method to integrate HRQoL data into the assessment of therapeutic agents. This proof of concept study utilizes data from the neoadjuvant I-SPY 2 clinical trial to describe the development of the Quality of Life Index (QoLI) measure. The QoLI represents a single composite score that incorporates validated longitudinal measures of clinical efficacy and QoL and one that permits a more comprehensive, direct comparison of individual therapeutic agents. Preliminary data suggest the QoLI is able to distinguish between agents based on their efficacy and toxicity; with further validation, the QoLI has the potential to provide more patient-centered evaluations in clinical trials and help guide treatment decision making in breast cancer and other oncologic diseases.
Impact of mixed biofilm formation with environmental microorganisms on E. coli O157:H7 survival against sanitization
Authors: Chitlapilly Dass Sapna , Bosilevac Joseph M. , Weinroth Maggie , Elowsky Christian G. , Zhou You , Anandappa Angela , Wang Rong 
Published: October 2020

AbstractBiofilm formation by foodborne pathogens is a serious threat to food safety and public health. Meat processing plants may harbor various microorganisms and occasional foodborne pathogens; thus, the environmental microbial community might impact pathogen survival via mixed biofilm formation. We collected floor drain samples from two beef plants with different E. coli O157:H7 prevalence history and investigated the effects of the environmental microorganisms on pathogen sanitizer tolerance. The results showed that biofilm forming ability and bacterial species composition varied considerably based on the plants and drain locations. E. coli O157:H7 cells obtained significantly higher sanitizer tolerance in mixed biofilms by samples from the plant with recurrent E. coli O157:H7 prevalence than those mixed with samples from the other plant. The mixed biofilm that best protected E. coli O157:H7 also had the highest species diversity. The percentages of the species were altered significantly after sanitization, suggesting that the community composition affects the role and tolerance level of each individual species. Therefore, the unique environmental microbial community, their ability to form biofilms on contact surfaces and the interspecies interactions all play roles in E. coli O157:H7 persistence by either enhancing or reducing pathogen survival within the biofilm community.
The structural role of osteocalcin in bone biomechanics and its alteration in Type-2 Diabetes
Authors: Tavakol Mahdi , Vaughan Ted J. 
Published: October 2020

AbstractThis study presents an investigation into the role of Osteocalcin (OC) on bone biomechanics, with the results demonstrating that the protein’s α-helix structures play a critical role in energy dissipation behavior in healthy conditions. In the first instance, α-helix structures have high affinity with the Hydroxyapatite (HAp) mineral surface and provide favorable conditions for adsorption of OC proteins onto the mineral surface. Using steered molecular dynamics simulation, several key energy dissipation mechanisms associated with α-helix structures were observed, which included stick–slip behavior, a sacrificial bond mechanism and a favorable binding feature provided by the Ca2+ motif on the OC protein. In the case of Type-2 Diabetes, this study demonstrated that possible glycation of the OC protein can occur through covalent crosslinking between Arginine and N-terminus regions, causing disruption of α-helices leading to a lower protein affinity to the HAp surface. Furthermore, the loss of α-helix structures allowed protein deformation to occur more easily during pulling and key energy dissipation mechanisms observed in the healthy configuration were no longer present. This study has significant implications for our understanding of bone biomechanics, revealing several novel mechanisms in OC’s involvement in energy dissipation. Furthermore, these mechanisms can be disrupted following the onset of Type-2 Diabetes, implying that glycation of OC could have a substantial contribution to the increased bone fragility observed during this disease state.
Infants’ gaze exhibits a fractal structure that varies by age and stimulus salience
Authors: Stallworthy Isabella C. , Sifre Robin , Berry Daniel , Lasch Carolyn , Smith Tim J. , Elison Jed T. 
Published: October 2020

AbstractThe development of selective visual attention is critical for effectively engaging with an ever-changing world. Its optimal deployment depends upon interactions between neural, motor, and sensory systems across multiple timescales and neurocognitive loci. Previous work illustrates the spatio-temporal dynamics of these processes in adults, but less is known about this emergent phenomenon early in life. Using data (n = 190; 421 visits) collected between 3 and 35 months of age, we examined the spatio-temporal complexity of young children’s gaze patterns as they viewed stimuli varying in semantic salience. Specifically, we used detrended fluctuation analysis (DFA) to quantify the extent to which infants’ gaze patterns exhibited scale invariant patterns of nested variability, an organizational feature thought to reflect self-organized and optimally flexible system dynamics that are not overly rigid or random. Results indicated that gaze patterns of even the youngest infants exhibited fractal organization that increased with age. Further, fractal organization was greater when children (a) viewed social stimuli compared to stimuli with degraded social information and (b) when they spontaneously gazed at faces. These findings suggest that selective attention is well-organized in infancy, particularly toward social information, and indicate noteworthy growth in these processes across the first years of life.
Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity
Authors: Panagiotou Stavros , Chaguza Chrispin , Yahya Reham , Audshasai Teerawit , Baltazar Murielle , Ressel Lorenzo , Khandaker Shadia , Alsahag Mansoor , Mitchell Tim J. , Prudhomme Marc , Kadioglu Aras , Yang Marie 
Published: October 2020

AbstractStreptococcus pneumoniae is a devastating global pathogen. Prevalent in sub-Saharan Africa, pneumococcal serotype 1 is atypical in that it is rarely found as a nasopharyngeal coloniser, yet is described as one of the most common causes of invasive pneumococcal disease. Clonal sequence type (ST)-306 and ST615 are representative of the two major serotype 1 lineages A and C, respectively. Here we investigated the virulence properties and haemolytic activities of these 2 clonal types using in vivo mouse models and in vitro assays. A lethal dose of ST615 administered intranasally to mice led to the rapid onset of disease symptoms and resulted in 90% mortality. In contrast, mice exposed to the same infection dose of ST306 or a pneumolysin (Ply)-deficient ST615 failed to develop any disease symptoms. Interestingly, the 2 strains did not differ in their ability to bind the immune complement or to undergo neutrophil-mediated phagocytosis. Upon comparative genomic analysis, we found higher within-ST sequence diversity in ST615 compared with ST306 and determined that ZmpA, ZmpD proteins, and IgA protease, were uniquely found in ST615. Using cell fractionation and cell contact-dependent assay, we made the unexpected finding that ST615 harbours the expression of two haemolytic variants of Ply: a cell-wall restricted fully haemolytic Ply, and a cytosolic pool of Ply void of any detectable haemolytic activity. This is the first time such a phenomenon has been described. We discuss the biological significance of our observation in relation to the aptitude of the pneumococcus for sustaining its human reservoir.
Skin hydration dynamics investigated by electrical impedance techniques in vivo and in vitro
Authors: Morin Maxim , Ruzgas Tautgirdas , Svedenhag Per , Anderson Christopher D. , Ollmar Stig , Engblom Johan , Björklund Sebastian 
Published: October 2020

AbstractSkin is easily accessible for transdermal drug delivery and also attractive for biomarker sampling. These applications are strongly influenced by hydration where elevated hydration generally leads to increased skin permeability. Thus, favorable transdermal delivery and extraction conditions can be easily obtained by exploiting elevated skin hydration. Here, we provide a detailed in vivo and in vitro investigation of the skin hydration dynamics using three techniques based on electrical impedance spectroscopy. Good correlation between in vivo and in vitro results is demonstrated, which implies that simple but realistic in vitro models can be used for further studies related to skin hydration (e.g., cosmetic testing). Importantly, the results show that hydration proceeds in two stages. Firstly, hydration between 5 and 10 min results in a drastic skin impedance change, which is interpreted as filling of superficial voids in skin with conducting electrolyte solution. Secondly, a subtle impedance change is observed over time, which is interpreted as leveling of the water gradient across skin leading to structural relaxation/changes of the macromolecular skin barrier components. With respect to transdermal drug delivery and extraction of biomarkers; 1 h of hydration is suggested to result in beneficial and stable conditions in terms of high skin permeability and extraction efficiency.
Multi-gene metabolic engineering of tomato plants results in increased fruit yield up to 23%
Authors: Vallarino José G. , Kubiszewski-Jakubiak Szymon , Ruf Stephanie , Rößner Margit , Timm Stefan , Bauwe Hermann , Carrari Fernando , Rentsch Doris , Bock Ralph , Sweetlove Lee J. , Fernie Alisdair R. 
Published: October 2020

AbstractThe capacity to assimilate carbon and nitrogen, to transport the resultant sugars and amino acids to sink tissues, and to convert the incoming sugars and amino acids into storage compounds in the sink tissues, are key determinants of crop yield. Given that all of these processes have the potential to co-limit growth, multiple genetic interventions in source and sink tissues, plus transport processes may be necessary to reach the full yield potential of a crop. We used biolistic combinatorial co-transformation (up to 20 transgenes) for increasing C and N flows with the purpose of increasing tomato fruit yield. We observed an increased fruit yield of up to 23%. To better explore the reconfiguration of metabolic networks in these transformants, we generated a dataset encompassing physiological parameters, gene expression and metabolite profiling on plants grown under glasshouse or polytunnel conditions. A Sparse Partial Least Squares regression model was able to explain the combination of genes that contributed to increased fruit yield. This combinatorial study of multiple transgenes targeting primary metabolism thus offers opportunities to probe the genetic basis of metabolic and phenotypic variation, providing insight into the difficulties in choosing the correct combination of targets for engineering increased fruit yield.
Small-scaled association between ambient temperature and campylobacteriosis incidence in Germany
Authors: Oberheim Julia , Höser Christoph , Lüchters Guido , Kistemann Thomas 
Published: October 2020

AbstractCampylobacteriosis is the leading bacterial cause of human diarrheal illness worldwide. Campylobacteriosis incidence exhibits seasonality and has been attributed to ambient temperature. However, the role of ambient temperature on campylobacteriosis remains poorly understood. To examine the impact of ambient temperature on local campylobacteriosis in Germany, weekly incidences on NUTS-3 level were analysed using a novel small-scaled approach, regression and time lags. Campylobacteriosis incidence correlated positively with temperatures between − 5 and 28 °C. The sigmoid regression model estimated an incidence increase of 0.52 per 5 °C temperature rise in the observation period. The weekly average of daily minimum temperature was most significant at a time lag of two weeks and showed the steepest incidence increase of 0.13 per 1 °C temperature increase in a temperature corridor of 5.1 to 12.2 °C. The impact of average minimum temperatures on campylobacteriosis incidence is crucial, likely to be indirect and especially relevant in the recent part of the infection chain. Vectors or human behaviour are presumably more directly linked with temperature than the pathogen’s microbiology and should be examined. These variables outweigh the direct temperature-pathogen relationship when the whole chain of infection is considered. In the context of climate change, campylobacteriosis is likely to increase in Germany due to an increased temperature effect.
Motif 1 Binding Protein suppresses wingless to promote eye fate in Drosophila
Authors: Raj Akanksha , Chimata Anuradha Venkatakrishnan , Singh Amit 
Published: October 2020

AbstractThe phenomenon of RNA polymerase II (Pol II) pausing at transcription start site (TSS) is one of the key rate-limiting steps in regulating genome-wide gene expression. In Drosophila embryo, Pol II pausing is known to regulate the developmental control genes expression, however, the functional implication of Pol II pausing during later developmental time windows remains largely unknown. A highly conserved zinc finger transcription factor, Motif 1 Binding Protein (M1BP), is known to orchestrate promoter-proximal pausing. We found a new role of M1BP in regulating Drosophila eye development. Downregulation of M1BP function suppresses eye fate resulting in a reduced eye or a “no-eye” phenotype. The eye suppression function of M1BP has no domain constraint in the developing eye. Downregulation of M1BP results in more than two-fold induction of wingless (wg) gene expression along with robust induction of Homothorax (Hth), a negative regulator of eye fate. The loss-of-eye phenotype of M1BP downregulation is dependent on Wg upregulation as downregulation of both M1BP and wg, by using wgRNAi, shows a significant rescue of a reduced eye or a “no-eye” phenotype, which is accompanied by normalizing of wg and hth expression levels in the eye imaginal disc. Ectopic induction of Wg is known to trigger developmental cell death. We found that upregulation of wg as a result of downregulation of M1BP also induces apoptotic cell death, which can be significantly restored by blocking caspase-mediated cell death. Our data strongly imply that transcriptional regulation of wg by Pol II pausing factor M1BP may be one of the important regulatory mechanism(s) during Drosophila eye development.
Plant secondary metabolites induced electron flux in microbial fuel cell: investigation from laboratory-to-field scale
Authors: Nath Dibyojyoty , Ghangrekar M. M. 
Published: October 2020

AbstractWastewater treatment coupled with electricity recovery in microbial fuel cell (MFC) prefer mixed anaerobic sludge as inoculum in anodic chamber than pure stain of electroactive bacteria (EAB), due to robustness and syntrophic association. Genetic modification is difficult to adopt for mixed sludge microbes for enhancing power production of MFC. Hence, we demonstrated use of eco-friendly plant secondary metabolites (PSM) with sub-lethal concentrations to enhance the rate of extracellular electron transfer between EAB and anode and validated it in both bench-scale as well as pilot-scale MFCs. The PSMs contain tannin, saponin and essential oils, which are having electron shuttling properties and their addition to microbes can cause alteration in cell morphology, electroactive behaviour and shifting in microbial population dynamics depending upon concentrations and types of PSM used. Improvement of 2.1-times and 3.8-times in power densities was observed in two different MFCs inoculated withEucalyptus-extract pre-treated mixed anaerobic sludge and pure culture ofPseudomonas aeruginosa, respectively, as compared to respective control MFCs operated without addingEucalyptus-extract to inoculum. WhenEucalyptus-extract-dose was spiked to anodic chamber (125 l) of pilot-scale MFC, treating septage, the current production was dramatically improved. Thus, PSM-dosing to inoculum holds exciting promise for increasing electricity production of field-scale MFCs.
A novel serine protease inhibitor as potential treatment for dry eye syndrome and ocular inflammation
Authors: Joossen Cedric , Baán Adrienn , Moreno-Cinos Carlos , Joossens Jurgen , Cools Nathalie , Lanckacker Ellen , Moons Lieve , Lemmens Kim , Lambeir Anne-Marie , Fransen Erik , Delputte Peter , Caljon Guy , Van Der Veken Pieter , Maes Louis , De Meester Ingrid , Kiekens Filip , Augustyns Koen , Cos Paul 
Published: October 2020

AbstractDry eye syndrome (DES), a multifactorial disorder which leads to ocular discomfort, visual disturbance and tear film instability, has a rising prevalence and limited treatment options. In this study, a newly developed trypsin-like serine protease inhibitor (UAMC-00050) in a tear drop formulation was evaluated to treat ocular inflammation. A surgical animal model of dry eye was employed to investigate the potential of UAMC-00050 on dry eye pathology. Animals treated with UAMC-00050 displayed a significant reduction in ocular surface damage after evaluation with sodium fluorescein, compared to untreated, vehicle treated and cyclosporine-treated animals. The concentrations of IL-1α and TNF-α were also significantly reduced in tear fluid from UAMC-00050-treated rats. Additionally, inflammatory cell infiltration in the palpebral conjunctiva (CD3 and CD45), was substantially reduced. An accumulation of pro-MMP-9 and a decrease in active MMP-9 were found in tear fluid from animals treated with UAMC-00050, suggesting that trypsin-like serine proteases play a role in activating MMP-9 in ocular inflammation in this animal model. Comparative qRT-PCR analyses on ocular tissue indicated the upregulation of tryptase, urokinase plasminogen activator receptor (uPAR) and protease-activated receptor 2 (PAR2). The developed UAMC-00050 formulation was stable up to 6 months at room temperature in the absence of light, non-irritating and sterile with compatible pH and osmolarity. These results provide a proof-of-concept for the in vivo modifying potential of UAMC-00050 on dry eye pathology and suggest a central role of trypsin-like serine proteases and PAR2 in dry eye derived ocular inflammation.
Species composition and invasion risks of alien ornamental freshwater fishes from pet stores in Klang Valley, Malaysia
Authors: Saba Abdulwakil Olawale , Ismail Ahmad , Zulkifli Syaizwan Zahmir , Halim Muhammad Rasul Abdullah , Wahid Noor Azrizal Abdul , Amal Mohammad Noor Azmai 
Published: October 2020

AbstractThe ornamental fish trade has been considered as one of the most important routes of invasive alien fish introduction into native freshwater ecosystems. Therefore, the species composition and invasion risks of fish species from 60 freshwater fish pet stores in Klang Valley, Malaysia were studied. A checklist of taxa belonging to 18 orders, 53 families, and 251 species of alien fishes was documented. Fish Invasiveness Screening Test (FIST) showed that seven (30.43%), eight (34.78%) and eight (34.78%) species were considered to be high, medium and low invasion risks, respectively. After the calibration of the Fish Invasiveness Screening Kit (FISK) v2 using the Receiver Operating Characteristics, a threshold value of 17 for distinguishing between invasive and non-invasive fishes was identified. As a result, nine species (39.13%) were of high invasion risk. In this study, we found that non-native fishes dominated (85.66%) the freshwater ornamental trade in Klang Valley, while FISK is a more robust tool in assessing the risk of invasion, and for the most part, its outcome was commensurate with FIST. This study, for the first time, revealed the number of high-risk ornamental fish species that give an awareness of possible future invasion if unmonitored in Klang Valley, Malaysia.