bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world Treatment Patterns and Outcomes in HR+/HER2+ Metastatic Breast Cancer Patients: A National Cancer Database Analysis
Authors: Statler Abby B. , Hobbs Brian P. , Wei Wei , Gupta Annie , Blake Cassann N. , Nahleh Zeina A. 
Published: December 2019

AbstractTreatment patterns and outcomes are unclear for metastatic breast cancer (MBC) patients diagnosed with hormone receptor-positive (HR+), human epidermal growth factor 2-positive (HER2+) disease. This study aimed to: (1) examine the utilization of first-line therapy among HR+/HER2+/MBC patients and (2) compare overall survival (OS) between the identified regimens. We analyzed National Cancer Database patients (HR+/HER2+/MBC) who were treated between 2010 and 2015. Multivariable logistic and Cox regression were used to: (1) identify independent predictors of treatment receipt and (2) determine significant prognostic factors for OS. Kaplan-Meier method and log-rank test were used to estimate and evaluate OS, respectively. Propensity scores were added to all multivariate OS models, thereby accounting for bias in treatment receipt. Of 6,234 patients analyzed, 3770 (60.5%) received hormonal therapy and 2464 (39.5%) received chemotherapy. Receipt of hormonal therapy was associated with older age, grade 1/grade 2 disease, no visceral involvement, higher comorbidity scores, and being white. Multivariate analysis suggest patients receiving hormonal therapy + anti-HER2 experienced improved OS, when compared to chemotherapy + anti-HER2 (HR: 0.74, p = 0.004). Overall, the cohort receiving hormonal therapy + anti-HER2 reported the highest 5-year OS (hormonal + anti-HER2: 47.5% vs. chemotherapy + anti-HER2: 39.8% vs. hormonal: 38.5% vs. chemotherapy: 36.3%, p < 0.001). Our findings suggest de-escalated therapy may be the preferred and potentially more effective care path for HR+/HER2+/MBC patients, signaling a need for randomized studies.
Demonstration of critical coupling in an active III-nitride microdisk photonic circuit on silicon
Authors: Tabataba-Vakili Farsane , Doyennette Laetitia , Brimont Christelle , Guillet Thierry , Rennesson Stéphanie , Damilano Benjamin , Frayssinet Eric , Duboz Jean-Yves , Checoury Xavier , Sauvage Sébastien , El Kurdi Moustafa , Semond Fabrice , Gayral Bruno , Boucaud Philippe 
Published: December 2019

AbstractOn-chip microlaser sources in the blue constitute an important building block for complex integrated photonic circuits on silicon. We have developed photonic circuits operating in the blue spectral range based on microdisks and bus waveguides in III-nitride on silicon. We report on the interplay between microdisk-waveguide coupling and its optical properties. We observe critical coupling and phase matching, i.e. the most efficient energy transfer scheme, for very short gap sizes and thin waveguides (g = 45 nm and w = 170 nm) in the spontaneous emission regime. Whispering gallery mode lasing is demonstrated for a wide range of parameters with a strong dependence of the threshold on the loaded quality factor. We show the dependence and high sensitivity of the output signal on the coupling. Lastly, we observe the impact of processing on the tuning of mode resonances due to the very short coupling distances. Such small footprint on-chip integrated microlasers providing maximum energy transfer into a photonic circuit have important potential applications for visible-light communication and lab-on-chip bio-sensors.
Oxygen consumption in seasonally stratified lakes decreases only below a marginal phosphorus threshold
Authors: Müller Beat , Steinsberger Thomas , Schwefel Robert , Gächter René , Sturm Michael , Wüest Alfred 
Published: December 2019

AbstractAreal oxygen (O2) consumption in deeper layers of stratified lakes and reservoirs depends on the amount of settling organic matter. As phosphorus (P) limits primary production in most lakes, protective and remediation efforts often seek to reduce P input. However, lower P concentrations do not always lead to lower O2 consumption rates. This study used a large hydrochemical dataset to show that hypolimnetic O2 consumption rates in seasonally stratified European lakes remain consistently elevated within a narrow range (1.06 ± 0.08 g O2 m−2 d−1) as long as areal P supply (APS) exceeded 0.54 ± 0.06 g P m−2 during the productive season. APS consists of the sum of total P present in the productive top 15 m of the water column after winter mixing plus the load of total dissolved P imported during the stratified season, normalized to the lake area. Only when APS sank below this threshold, the areal hypolimnetic mineralization rate (AHM) decreased in proportion to APS. Sediment trap material showed increasing carbon:phosphorus (C:P) ratios in settling particulate matter when APS declined. This suggests that a decreasing P load results in lower P concentration but not necessarily in lower AHM rates because the phytoplankton community is able to maintain maximum biomass production by counteracting the decreasing P supply by a more efficient P utilization. In other words, in-lake organic matter production depends only on APS if the latter falls below the threshold of 0.54 g P m−2 and correspondingly, the atomic C:P ratio of the settling material exceeds ~155.
Fluctuating renal function and the risk of incident atrial fibrillation: a nationwide population-based study
Authors: Kwon Soonil , Lee So-Ryoung , Choi Eue-Keun , Han Kyung-Do , Yang Seokhun , Lee Seo-Young , Lee Hyun-Jung , Moon Inki , Lee Euijae , Cha Myung-Jin , Lim Woo-Hyun , Oh Seil , Lip Gregory Y. H. 
Published: December 2019

AbstractAlthough chronic kidney disease is known to increase the risk of atrial fibrillation (AF), the impact of the variability of renal function on the risk of incident AF is unknown. We aimed to evaluate the association between variability of renal function and the risk of developing AF among the general population. We evaluated a total of 3,551,249 adults who had three annual health check-ups provided by the National Health Insurance Service. The variability of renal function was defined as GFR-VIM, which is variability independent of the mean (VIM) of creatinine-based estimated glomerular filtration rate (eGFR). The study population was divided into four groups (Q1-4) based on the quartiles of GFR-VIM, and the risks of incident AF by each group were compared. During a mean of 3.2 ± 0.5 years follow-up, incident AF occurred in 15,008 (0.42%) subjects. The incidence rates of AF increased from Q1 to Q4 (0.98, 1.42, 1.27, and 1.63 per 1,000 person-years, respectively). Adjusting with multiple variables, Q4 showed an increased risk of incident AF compared to Q1 (hazard ratio (HR) 1.125, 95% confidence interval (CI) 1.071–1.181). Variability of serum creatinine or other definitions of variability showed consistent results. On subgroup analyses, Q4 in males or those with a decreasing trend of eGFR had significantly increased risks of incident AF compared to Q1 (HR 1.127, 95% CI 1.082–1.175; and HR 1.115, 95% CI 1.059–1.173, respectively). High variability of eGFR was associated with an increased risk of incident AF, particularly in males or those with decreasing trends of eGFR during follow-up.
Modeling reservoir management for malaria control in Ethiopia
Authors: Kibret Solomon , Ryder Darren , Wilson G. Glenn , Kumar Lalit 
Published: December 2019

AbstractThis study investigated how changes in reservoir water level affect mosquito abundance and malaria transmission in Ethiopia. Digital elevation models of three Ethiopian dams at lowland, midland and highland elevations were used to quantify water surface area and wetted shoreline at different reservoir water levels (70, 75, 80, 85, 90, 95 and 100% full capacity) to estimate surface area of potential mosquito breeding habitat. Reservoir water level drawdown rates of 10, 15 and 20 mm.day−1 were applied as scenarios to model larval abundance, entomological inoculation rate (EIR) and malaria prevalence at each dam. Malaria treatment cost and economic cost in terms of lost working days were calculated for each water level scenario and dam. At the lowland dam, increased larval abundances were associated with increasing reservoir water level and wetted shoreline area. In contrast, both larval abundances and area of wetted shoreline declined with increasing reservoir water level at the midland and highland dams. Estimated EIR, malaria prevalence, malaria treatment cost and economic cost generally decreased when the water level drawdown rate increased from 10 to 15 and 20 mm.day−1 irrespective of reservoir water level. Given the expansion of dam construction in sub-Saharan Africa, incorporating malaria control measures such as manipulating drawdown rates into reservoir management has the potential to reduce the malaria burden and health care costs in communities near reservoirs.
Inhibitory characteristics of flavonol-3-O-glycosides from Polygonum aviculare L. (common knotgrass) against porcine pancreatic lipase
Authors: Park Jun-Young , Kim Chung Sun , Park Kyung-Min , Chang Pahn-Shick 
Published: December 2019

AbstractPancreatic lipase (PL) is an enzyme that plays an essential role in the digestion of dietary lipids and is a suitable target for an anti-obesity dietary supplement. The objective of this study was to find a novel source of PL inhibitors from Korean medicinal plants and investigate the PL-inhibitory properties of the active constituents. From among 34 kinds of methanolic crude extracts, Polygonum aviculare L. showed the highest PL-inhibitory activity (63.97 ± 0.05% of inhibition). Solvent fractionation and liquid chromatography/mass spectrometry (LC/MS) analysis identified flavonol-3-O-glycosides, flavonol-3-O-(2″-galloyl)-glycosides, and flavonol aglycones as active constituents. Furthermore, the inhibitory characteristics of the major compounds were investigated in terms of enzyme kinetics and fluorescence quenching. The results suggested that the inhibitory activity of the major compounds is closely related to the tertiary structural change in PL, and that differences in inhibitory activity occurred due to slight discrepancies in their chemical structure.
Optimal gestational weight gain for underweight pregnant women in Japan
Authors: Shindo Ryosuke , Aoki Mihoko , Yamamoto Yuriko , Misumi Toshihiro , Miyagi Etsuko , Aoki Shigeru 
Published: December 2019

AbstractWe aimed to investigate the optimal range of gestational weight gain (GWG) for Japanese underweight (body mass index <18.5 kg/m2) women using the Japanese Birth Registry System. The study subjects included underweight women who were divided into groups according to the GWG recommendations of the Ministry of Health, Labour and Welfare (MHLW) (9–12 kg): <9.0 kg, group A; 9–12 kg, group B; and >12 kg, group C. The subjects were then classified according to the recommendations of the Institute of Medicine (IOM) (12.7–18.1 kg): <12.7 kg, group D; 12.7–18.1 kg, group E; and >18.1 kg, group F. In total, 148,135 cases were analysed. The frequencies of small for gestational age, preterm delivery, and caesarean delivery were as follows: 19.3%, 22.7%, and 28.5% for group A; 11.7%, 8.7%, and 22.8% for group B; 8.0%, 4.9%, and 21.5% for group C; 15.0%, 14.7%, and 25.2% for group D; 8.0%, 5.3%, and 21.5% for group E; and 7.0%, 5.5%, and 25.0% for group F, respectively. These results indicated that groups C and E had the best outcomes. Therefore, the IOM guidelines seem more appropriate than the MHLW guidelines. Therefore, the MHLW recommended GWG guidelines require revision.
The Effect of pH on Antibiotic Efficacy against Coxiella burnetii in Axenic Media
Authors: Smith Cody B. , Evavold Charles , Kersh Gilbert J. 
Published: December 2019

AbstractCoxiella burnetii, the etiologic agent of Q fever, replicates in an intracellular phagolysosome with pH between 4 and 5. The impact of this low pH environment on antimicrobial treatment is not well understood. An in vitro system for testing antibiotic susceptibility of C. burnetii in axenic media was set up to evaluate the impact of pH on C. burnetii growth and survival in the presence and absence of antimicrobial agents. The data show that C. burnetii does not grow in axenic media at pH 6.0 or higher, but the organisms remain viable. At pH of 4.75, 5.25, and 5.75 moxifloxacin, doxycycline, and rifampin are effective at preventing growth of C. burnetii in axenic media, with moxifloxacin and doxycycline being bacteriostatic and rifampin having bactericidal activity. The efficacy of doxycycline and moxifloxacin improved at higher pH, whereas rifampin activity was pH independent. Hydroxychloroquine is thought to inhibit growth of C. burnetii in vivo by raising the pH of typically acidic intracellular compartments. It had no direct bactericidal or bacteriostatic activity on C. burnetii in axenic media, suggesting that raising pH of acidic intracellular compartments is its primary mechanism of action in vivo. The data suggest that doxycycline and hydroxychloroquine are primarily independent bacteriostatic agents.
Projecting the impact of variable MDR-TB transmission efficiency on long-term epidemic trends in South Africa and Vietnam
Authors: Salvatore Phillip P. , Kendall Emily A. , Seabrook Dena , Brown Jessie , Durham George H. , Dowdy David W. 
Published: December 2019

AbstractWhether multidrug-resistant tuberculosis (MDR-TB) is less transmissible than drug-susceptible (DS-)TB on a population level is uncertain. Even in the absence of a genetic fitness cost, the transmission potential of individuals with MDR-TB may vary by infectiousness, frequency of contact, or duration of disease. We used a compartmental model to project the progression of MDR-TB epidemics in South Africa and Vietnam under alternative assumptions about the relative transmission efficiency of MDR-TB. Specifically, we considered three scenarios: consistently lower transmission efficiency for MDR-TB than for DS-TB; equal transmission efficiency; and an initial deficit in the transmission efficiency of MDR-TB that closes over time. We calibrated these scenarios with data from drug resistance surveys and projected epidemic trends to 2040. The incidence of MDR-TB was projected to expand in most scenarios, but the degree of expansion depended greatly on the future transmission efficiency of MDR-TB. For example, by 2040, we projected absolute MDR-TB incidence to account for 5% (IQR: 4–9%) of incident TB in South Africa and 14% (IQR: 9–26%) in Vietnam assuming consistently lower MDR-TB transmission efficiency, versus 15% (IQR: 8–27%)and 41% (IQR: 23–62%), respectively, assuming shrinking transmission efficiency deficits. Given future uncertainty, specific responses to halt MDR-TB transmission should be prioritized.
Simple oral mucosal epithelial transplantation in a rabbit model
Authors: Inamochi Aya , Tomioka Akiko , Kitamoto Kohdai , Miyai Takashi , Usui Tomohiko , Aihara Makoto , Yamagami Satoru 
Published: December 2019

AbstractThis study investigated a rabbit model of autologous simple oral mucosal epithelium transplantation (SOMET) for limbal stem cell deficiency (LSCD). LSCD was created in the SOMET group and the Control group. In the SOMET group, oral mucosa harvested from the buccal region was treated with dispase, cut into small pieces, and placed on the exposed corneal stroma without using graft sutures, amniotic membrane, and/or glue. A soft contact lens was positioned and tarsorrhaphy was performed in both groups. Postoperative corneal neovascularization and fluorescein staining scores were evaluated by slit lamp microscopy in both groups. At 2 weeks postoperatively, eyes were excised and subjected to immunohistochemical staining for CK3, CK13, CK15, and p63. In the SOMET group, transplantation of oral mucosa led to complete recovery of LSCD, as indicated by low neovascularization scores, low fluorescein staining scores, and detection of stratified K3/K13-positive cells on the stroma at 2 weeks after surgery. In contrast, corneal epithelial defects persisted in the Control group at 2 weeks. SOMET achieved re-epithelialization of the corneal surface in this rabbit LSCD model. It is a simple technique that does not require culture and could be a promising option for ocular surface reconstruction in bilateral LSCD.
6-Bromoindirubin-3′-oxime intercepts GSK3 signaling to promote and enhance skeletal muscle differentiation affecting miR-206 expression in mice
Authors: Ragozzino Elvira , Brancaccio Mariarita , Di Costanzo Antonella , Scalabrì Francesco , Andolfi Gennaro , Wanderlingh Luca G. , Patriarca Eduardo J. , Minchiotti Gabriella , Altamura Sergio , Summa Vincenzo , Varrone Francesca 
Published: December 2019

AbstractDystrophies are characterized by progressive skeletal muscle degeneration and weakness as consequence of their molecular abnormalities. Thus, new drugs for restoring skeletal muscle deterioration are critically needed. To identify new and alternative compounds with a functional role in skeletal muscle myogenesis, we screened a library of pharmacologically active compounds and selected the small molecule 6-bromoindirubin-3′-oxime (BIO) as an inhibitor of myoblast proliferation. Using C2C12 cells, we examined BIO’s effect during myoblast proliferation and differentiation showing that BIO treatment promotes transition from cell proliferation to myogenic differentiation through the arrest of cell cycle. Here, we show that BIO is able to promote myogenic differentiation in damaged myotubes in-vitro by enriching the population of newly formed skeletal muscle myotubes. Moreover, in-vivo experiments in CTX-damaged TA muscle confirmed the pro-differentiation capability of BIO as shown by the increasing of the percentage of myofibers with centralized nuclei as well as by the increasing of myofibers number. Additionally, we have identified a strong correlation of miR-206 with BIO treatment both in-vitro and in-vivo: the enhanced expression of miR-206 was observed in-vitro in BIO-treated proliferating myoblasts, miR-206 restored expression was observed in a forced miR-206 silencing conditions antagomiR-mediated upon BIO treatment, and in-vivo in CTX-injured muscles miR-206 enhanced expression was observed upon BIO treatment. Taken together, our results highlight the capacity of BIO to act as a positive modulator of skeletal muscle differentiation in-vitro and in-vivo opening up a new perspective for novel therapeutic targets to correct skeletal muscle defects.
Fluorescence imaging reversion using spatially variant deconvolution
Authors: Anastasopoulou Maria , Gorpas Dimitris , Koch Maximilian , Liapis Evangelos , Glasl Sarah , Klemm Uwe , Karlas Angelos , Lasser Tobias , Ntziachristos Vasilis 
Published: December 2019

AbstractFluorescence imaging opens new possibilities for intraoperative guidance and early cancer detection, in particular when using agents that target specific disease features. Nevertheless, photon scattering in tissue degrades image quality and leads to ambiguity in fluorescence image interpretation and challenges clinical translation. We introduce the concept of capturing the spatially-dependent impulse response of an image and investigate Spatially Adaptive Impulse Response Correction (SAIRC), a method that is proposed for improving the accuracy and sensitivity achieved. Unlike classical methods that presume a homogeneous spatial distribution of optical properties in tissue, SAIRC explicitly measures the optical heterogeneity in tissues. This information allows, for the first time, the application of spatially-dependent deconvolution to correct the fluorescence images captured in relation to their modification by photon scatter. Using experimental measurements from phantoms and animals, we investigate the improvement in resolution and quantification over non-corrected images. We discuss how the proposed method is essential for maximizing the performance of fluorescence molecular imaging in the clinic.
Synthesis and biological activities of two camptothecin derivatives against Spodoptera exigua
Authors: Yang Fulai , Wang Liping , Zhang Lan , Zhang Yanning , Mao Liangang , Jiang Hongyun 
Published: December 2019

AbstractCamptothecin (CPT), a natural alkaloid isolated from Camptotheca acuminata Decne, is found to show potential insecticidal activities with unique action mechanisms by targeting at DNA-topoisomease I (Top1) complex and inducing cell apoptosis. To improve the efficacy against insect pests, two camptothecin (CPT) derivatives were synthesized through introducing two functional groups, 2-nitroaminoimidazoline and 1-chloro-2-isocyanatoethane by esterification reaction. The insecticidal activities of these two derivatives were evaluated at contact toxicity, cytotoxicity and topoisomerase I (Top1) inhibitory activities comparing with CPT and hydroxyl-camptothecin (HCPT). Results showed that compound a, synthesized by introducing 2-nitroaminoimidazoline to CPT, apparently increased contact toxicity to the third larvae of beet armyworm, Spodoptera exigua, and cytotoxicity to IOZCAS-Spex-II cells isolated from S. exigua. However, the inhibition on DNA relaxation activity of Top1 was reduced to less than 5 percentage even at high concentrations (50 and 100 μM). For introducing 1-chloro-2-isocyanatoethane to HCPT, the contact toxicity, cytotoxicity and Top1 inhibitory activity of synthesized compound b were increased significantly compared to CPT and HCPT. These results suggested that both synthesized compounds possessed high efficacy against S. exigua by targeting at Top1 (compound b) or novel mechanism of action (compound a).
TAS2R38 bitter taste receptor and attainment of exceptional longevity
Authors: Melis Melania , Errigo Alessandra , Crnjar Roberto , Pes Giovanni Mario , Tomassini Barbarossa Iole 
Published: December 2019

AbstractBitter taste receptors play crucial roles in detecting bitter compounds not only in the oral cavity, but also in extraoral tissues where they are involved in a variety of non‒tasting physiological processes. On the other hand, disorders or modifications in the sensitivity or expression of these extraoral receptors can affect physiological functions. Here we evaluated the role of the bitter receptor TAS2R38 in attainment of longevity, since it has been widely associated with individual differences in taste perception, food preferences, diet, nutrition, immune responses and pathophysiological mechanisms. Differences in genotype distribution and haplotype frequency at the TAS2R38 gene between a cohort of centenarian and near-centenarian subjects and two control cohorts were determined. Results show in the centenarian cohort an increased frequency of subjects carrying the homozygous genotype for the functional variant of TAS2R38 (PAV/PAV) and a decreased frequency of those having homozygous genotype for the non-functional form (AVI/AVI), as compared to those determined in the two control cohorts. In conclusion, our data providing evidence of an association between genetic variants of TAS2R38 gene and human longevity, suggest that TAS2R38 bitter receptor can be involved in the molecular physiological mechanisms implied in the biological process of aging.