bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent janus kinase‐signaling in chronic lymphocytic leukemia patients on ibrutinib: Results of a phase I trial
Authors: Spaner David E. , McCaw Lindsay , Wang Guizhei , Tsui Hubert , Shi Yonghong 
Published: March 2019

AbstractMethods to deepen clinical responses to ibrutinib are needed to improve outcomes for patients with chronic lymphocytic leukemia (CLL). This study aimed to determine the safety and efficacy of combining a janus kinase (JAK)‐inhibitor with ibrutinib because JAK‐mediated cytokine‐signals support CLL cells and may not be inhibited by ibrutinib. The JAK1/2 inhibitor ruxolitinib was prescribed to 12 CLL patients with abnormal serum beta‐2 microglobulin levels after 6 months or persistent lymphadenopathy or splenomegaly after 12 months on ibrutinib using a 3 + 3 phase 1 trial design (NCT02912754). Ibrutinib was continued at 420 mg daily and ruxolitinib was added at 5, 10, 15, or 20 mg BID for 3 weeks out of five for seven cycles. The break was mandated to avoid anemia and thrombocytopenia observed with ruxolitinib as a single agent in CLL. The combination was well‐tolerated without dose‐limiting toxicities. Cyclic changes in platelets, lymphocytes, and associated chemokines and thrombopoietic factors were observed and partial response criteria were met in 2 of 12 patients. The results suggest that JAK‐signaling helps CLL cells persist in the presence of ibrutinib and ruxolitinib with ibrutinib is well‐tolerated and may be a useful regiment to use in combination therapies for CLL.
Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer
Authors: Chen Yibing , Wang Dandan , Song Yucen , Zhang Xiaofei , Jiao Zhihui , Dong Juqin , Lü Lin , Zou Zhengzhi , Du Wei , Qu Falin 
Published: March 2019

AbstractBackgroundCircadian positive feedback loop (CPFL) genes (CLOCK, BAML1, and NPAS2) have been implicated in cancer initiation and progression. The purpose of this study was to explore the effects of single‐nucleotide polymorphisms (SNPs) in CPFL genes on prognosis of gastric cancer (GC) patients.MethodsNine functional SNPs from the three CPFL genes were genotyped in a cohort of 704 GC patients undergoing resection. Multivariate Cox regression model and Kaplan‐Meier curve were used for prognosis analysis.ResultsAmong the nine SNPs, rs11133399 in CLOCK, rs1044432 and rs2279284 in BAML1 were significantly associated with GC overall survival and recurrence‐free survival. The unfavorable genotypes of these SNPs showed a cumulative effect on GC prognosis. Multivariate assessment model indicated that these SNPs, in conjunction with clinical variables, enhanced the power to predict GC prognosis. In addition, survival tree analysis revealed the genotype of rs11133399 as a primary risk factor contributing to the prognosis of GC patients. Functional assays showed that the G allele in rs11133399 significantly enhanced luciferase reporter activity than A allele. Immunohistochemical analysis further demonstrated that the genotype of rs11133399 was significantly associated with the expression level of CLOCK in GC tissues, suggesting that this SNP might affect the prognosis of GC through its influence on the expression of CLOCK gene.ConclusionsOur data indicate that SNPs in CPFL genes might contribute to the clinical outcome of GC through their impact on gene expression. Further studies are needed to elucidate its underlying molecular mechanisms.
Disparities in colorectal cancer screening in New York City: An analysis of the 2014 NYC Community Health Survey
Authors: Rastogi Neelesh , Xia Yuhe , Inadomi John M. , Kwon Simona C. , Trinh‐Shevrin Chau , Liang Peter S. 
Published: March 2019

AbstractBackground & AimsDisparities in colorectal cancer (CRC) screening uptake by race/ethnicity, socioeconomic status, and geography are well documented. We sought to further characterize the relationship between sociodemographic factors and up‐to‐date colonoscopy use in a diverse urban center using the 2014 New York City Community Health Survey (NYCCHS).MethodsWe examined overall colonoscopy uptake by race/ethnicity—with a particular interest in Asian and Hispanic subgroups—and used weighting to represent the entire 2014 NYC adult population. We also evaluated the association between 10 sociodemographic variables (age, sex, race/ethnicity, birthplace, home language, time living in the US, education, employment, income, and borough of residence) and colonoscopy use using univariable and multivariable logistic regression models.ResultsUp‐to‐date colonoscopy uptake was 69% overall with reported differences by racial/ethnic group, ranging from 44%‐45% for Mexicans and Asian Indians to 75% for Dominicans. In the multivariable regression model, colonoscopy use was associated with age greater than 65 years, Chinese language spoken at home, and not being in the labor force. Lower colonoscopy use was associated with living in the US for less than 5 years, Asian Indian language spoken at home, lower income, and residing outside of Manhattan.ConclusionsAmong New Yorkers older than age 50, up‐to‐date colonoscopy use varied significantly by race/ethnicity, especially in Asian and Hispanic subgroups. Recent immigrants, low‐income groups, and those living outside of Manhattan were significantly less likely to receive CRC screening. Targeted interventions to promote CRC screening in these underserved groups may improve overall screening uptake.
Design and Synthesis of Novel Cytotoxic Indole‐Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study
Authors: Bakherad Zohreh , Safavi Maliheh , Fassihi Afshin , Sadeghi‐Aliabadi Hojjat , Bakherad Mohammad , Rastegar Hossein , Saeedi Mina , Ghasemi Jahan B , Saghaie Lotfollah , Mahdavi Mohammad 
Published: March 2019

AbstractIn this work, two novel series of indole‐thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF‐7, A‐549, and Hep‐G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A‐549 and Hep‐G2 than MCF‐7. Among them, (2E)‐2‐{[2‐(4‐chlorophenyl)‐1H‐indol‐3‐yl]methylidene}‐N‐(4‐methoxyphenyl)hydrazinecarbothioamide (8l) was found to be the most potent compound against A‐549 and Hep‐G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A‐549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.
Strangulated recurrent rectal prolapse after a Delorme intervention, a case report
Authors: Malibary Nadim , Brigand Cecile 
Published: March 2019

Key Clinical MessageA surgeon must be aware of indications of rectal prolapse surgery with proper preoperative evaluation and have the ability to recognize complications. Sigmoid redundancy might lead to early recurrence, which itself could complicate into strangulation. Complications per say might require more drastic measures, as Hartmann's procedure in this case.
Confronting the Challenges of Next‐Generation Silicon Anode‐Based Lithium‐Ion Batteries: Role of Designer Electrolyte Additives and Polymeric Binders
Authors: Eshetu Gebrekidan Gebresilassie , Figgemeier Egbert 
Published: March 2019

AbstractSilicon has emerged as the next‐generation anode material for high‐capacity lithium‐ion batteries (LIBs). It is currently of scientific and practical interest to encounter increasingly growing demands for high energy/power density electrochemical energy‐storage devices for use in electric vehicles (xEVs), renewable energy sources, and smart grid/utility applications. Improvements to existing conventional LIBs are required to provide higher energy, longer cycle lives. This is attributed to its unparalleled theoretical capacity (4200 mAh g−1 for Li4.4Si), which is approximately 10 times higher than that of a state‐of‐the‐art graphitic anode (372 mAh g−1 for LiC6), with a suitable operating voltage, natural abundance, environmental benignity, nontoxicity, high safety, and so forth. However, despite the overwhelming beneficial features, the practical integration of LIBs containing a silicon anode beyond the commercial niche is hampered by unavoidable challenges, such as excessive volume changes during the (de‐)alloying process, inherently low electrical and ionic conductivities, an unstable solid–electrolyte interphase, and electrolyte drying out. Among various extenuating strategies, non‐electrode factors encompassing electrolyte additives and polymeric binders are regarded as the most economical, and effective approaches towards circumventing these disadvantages are in short supply. With the aim of providing an in‐depth insight into rapidly growing accounts of electrolyte additives and binders for use with silicon anode‐based LIBs, this Review assesses the current state of the art of research and thereby examines opportunities to open up new avenues for the practical realization of these silicon anode‐based LIBs.
The synthetic cathinone psychostimulant α‐PPP antagonizes serotonin 5‐HT2A receptors: In vitro and in vivo evidence
Authors: Chen Yiming , Blough Bruce E. , Murnane Kevin S. , Canal Clinton E. 
Published: March 2019

AbstractSynthetic cathinones (SCs) are β‐keto analogs of amphetamines. Like amphetamines, SCs target monoamine transporters; however, unusual neuropsychiatric symptoms have been associated with abuse of some SCs, suggesting SCs might possess additional pharmacological properties. We performed radioligand competition binding assays to assess the affinities of nine SCs at human 5‐HT2A receptors (5‐HT2AR) and muscarinic M1 receptors (M1R) transiently expressed in HEK293 cells. None of the SCs exhibited affinity at M1R (minimal displacement of [~Kd] [3H]scopolamine up to 10 μM). However, two SCs, α‐pyrrolidinopropiophenone (α‐PPP) and 4‐methyl‐α‐PPP, had low μM Ki values at 5‐HT2AR. In 5‐HT2AR–phosphoinositide hydrolysis assays, α‐PPP and 4‐methyl‐α‐PPP displayed inverse agonist activity. We further assessed the 5‐HT2AR functional activity of α‐PPP, and observed it competitively antagonized 5‐HT2AR signaling stimulated by the 5‐HT2R agonist (±)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI; Kb = 851 nM). To assess in vivo 5‐HT2AR activity, we examined the effects of α‐PPP on the DOI‐elicited head‐twitch response (HTR) in mice. α‐PPP dose‐dependently blocked the HTR with maximal suppression at 10 mg/kg (P < 0.0001), which is a moderate dose used in studies investigating psychostimulant properties of α‐PPP. To corroborate a 5‐HT2AR mechanism, we also tested 3,4‐methylenedioxy‐α‐PPP (MDPPP) and 3‐bromomethcathinone (3‐BMC), SCs that we observed had 5‐HT2AR Kis > 10 μM. Neither MDPPP nor 3‐BMC, at 10 mg/kg doses, attenuated the DOI HTR. Our results suggest α‐PPP has antagonist interactions at 5‐HT2AR in vitro that may translate at physiologically‐relevant doses in vivo. Considering 5‐HT2AR antagonism has been shown to mitigate effects of psychostimulants, this property may contribute to α‐PPPs unpopularity compared to other monoamine transporter inhibitors.
IPM2: toward better understanding and forecasting of population dynamics
Authors: Plard Floriane , Turek Daniel , Grüebler Martin U. , Schaub Michael 
Published: March 2019

AbstractDynamic population models typically aim to predict demography and the resulting population dynamics in relation to environmental variation. However, they rarely include the diversity of individual responses to environmental changes, thus hampering our understanding of demographic mechanisms. We develop an integrated integral projection model (IPM2) that is a combination of an integrated population model (IPMpop) and an integral projection model (IPMind). IPM2 includes interactions between environmental and individual effects on demographic rates and can forecast both population size and individual trait distributions. First, we study the performance of this model using eight simulated scenarios with variable reproductive selective pressures on an individual trait. When the individual trait interacts with the environmental variable and the selective pressure on the individual trait is nonlinear, only IPM2 produces adequate predictions, because IPMind does not link predictions between the population level and observed data and because IPMpop does not include the individual trait. Second, we apply IPM2 to a population of barn swallows. The model accurately predicts trends of the barn swallow population while also providing mechanistic insights. High precipitation negatively influenced population dynamics through delaying laying dates, which lowered reproductive and survival rates. To predict the future of populations, we need to understand their individual drivers and thus include individual responses to their environment while following the entire population. As a consequence, IPM2 will improve our ability to test ecological and evolutionary hypotheses and improve the accuracy of population forecasting to aid management programs.
Observations of a novel predatory gull behavior on an invasive ascidian: A new consequence of coastal urban sprawl?
Authors: Holman Luke E. , Rius Marc , Blackburn Tim M. 
Published: March 2019

AbstractCoastal urbanization has a dramatic effect on both terrestrial and marine ecosystems, altering resources such as food or space. Many species have shifted their ranges in response to anthropogenic pressures, resulting in novel species interactions. Here, we report an observation of a novel foraging behavior of the European Herring Gull (Larus argentatus): the capture and consumption of the widespread sea squirt Ciona intestinalis from under floating pontoons in a recreational marina in Ireland. Multiple gulls were observed performing a complex, multi‐step manipulation of several C. intestinalis individuals to remove their cellulose‐based tunic, which remained unconsumed. Further avenues of investigation are discussed, and hypotheses concerning possible ecosystem effects of novel ecological interactions occurring in proliferating artificial environments are presented.
NH2‐Functionalized Multi Walled Carbon Nanotubes Decorated with ZnO Nanoparticles and Graphene Quantum Dots for Sensitive Assay of Pimozide
Authors: Aftab Saima , Kurbanoglu Sevinc , Ozcelikay Goksu , Shah Afzal , Ozkan Sibel A. 
Published: March 2019

AbstractIn this study, a novel and sensitive electrochemical nanosensor for the determination of antipsychotic drug Pimozide (PZ) is proposed using NH2functionalized multi walled carbon nanotubes (NH2fMWCNT) decorated with and ZnO nanoparticles (ZnONPs) co‐catalyzed by graphene quantum dots (GQDs). Prior to electrochemical analyses of PZ, the designed nanosensor was well characterized in terms of surface morphology by scanning electron microscopy (SEM) and SEM armed with EDX analysis. Electrochemical impedance spectroscopy (EIS) employed to investigate the electron transfer capability and cyclic voltammetry (CV) technique was used to successfully compare the redox response of PZ on the surface of modified and unmodified electrode. The designed nanosensor response was linear between 6.25×10−11–1.20×10−7 M concentration range of PZ with a limit of detection value as 1.02×10−11 M. The influence of interfering agents was further studied to examine the selectivity of the designed sensor. A rapid screening of PZ as is required in pharmaceutical and biological samples underscores the paramount importance of nano based electrochemical sensor for its sensitive and selective detection.
Reference values for handgrip strength and their association with intrinsic capacity domains among older adults
Authors: Ramírez‐Vélez Robinson , Correa‐Bautista Jorge Enrique , García‐Hermoso Antonio , Cano Carlos Alberto , Izquierdo Mikel 
Published: March 2019

AbstractObjectiveThe purposes of this study were three‐fold: (i) to describe handgrip strength in older individuals aged ≥60 years in Colombia; (ii) to identify sex‐specific and age‐specific muscle weakness cut‐off points in older adults; and (iii) to determine the odds of adverse events for each of the intrinsic capacity domains for individuals with handgrip strength greater than the muscle weakness cut‐off points, as compared with their weaker counterparts.MethodsA cross‐sectional study was conducted in Colombia, among 5237 older adults aged ≥60 years old (58.5% women, 70.5 ± 7.8 years), according to ‘SABE Survey 2015’. Handgrip strength data were obtained with a Takei dynamometer. Sociodemographic variables, five domains of intrinsic capacity (i.e. locomotion, vitality, cognition, psychological, and sensory), and medical conditions were assessed and analyzed. Adjustments variables were age, ethnicity, socio‐economic status, urbanicity, body mass index, smoking status, alcohol intake, drug use, physical activity, and co‐morbid chronic diseases. Sex‐stratified analyses were conducted with logistic regression models.ResultsHandgrip strength was greater among men than among women (26.7 ± 8.5 vs. 16.7 ± 5.7 kg, respectively, P < 0.001) at all ages. Weak handgrip strength cut‐off points ranged from 17.4 to 8.6 and from 10.1 to 4.9 in men and women, respectively. Overall, participants with optimal handgrip strength had better intrinsic capacity [in men, odds ratio (OR) = 0.62, 95% confidence interval (CI) 0.53 to 0.71; P < 0.001; and in women, OR = 0.79, 95% CI 0.68 to 0.92; P = 0.002] than their weaker counterparts. Also, men with optimal handgrip strength had a lower risk of hospitalization (OR = 0.47, 95% CI 0.29 to 0.78; P = 0.004) than their weaker counterparts.ConclusionsThis study is the first to describe handgrip strength values and cut‐off points for muscle weakness among a nationally representative sample of Colombian older adults by age and sex. After categorizing older adults as weak or not weak based on the handgrip cut‐off points, non‐weakness was associated with a decreased odds of intrinsic capacity impairments. These cut‐off points may be good candidates for clinical assessment of risks to physical and mental health in older Colombian adults.
Cell therapy to improve regeneration of skeletal muscle injuries
Authors: Qazi Taimoor H. , Duda Georg N. , Ort Melanie J. , Perka Carsten , Geissler Sven , Winkler Tobias 
Published: March 2019

AbstractDiseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell‐based approaches have shown the most promising results in numerous pre‐clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non‐myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real‐life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell‐based solutions for treating traumatic muscle injuries—a so far unmet clinical need.
A cell retention system composed of cellulose acetate hollow fiber membranes for cultivation of Dunaliella salina in a helical photobioreactor
Authors: Ershad Ghazaleh Amini , Jazini Mohammadhadi , Fashandi Hossein , Shariati Mansour 
Published: March 2019

AbstractBackgroundOne of the challenges in commercial‐scale cultivation of Dunaliella salina is low biomass productivity and concentration. In addition, cultivations in wastewaters may encounter some nutrient limitations. Hence, there is a need for a cultivation system which is capable of continuous provision of nutrients while the cells are retained in the system. In this study, the feasibility of using a cell retention system (CRS) for increasing biomass productivity and concentration of D. salina was investigated. The CRS was composed of cellulose acetate hollow fiber membranes (HFMs) coupled with a helical photobioreactor.ResultsUsing the produced HFMs with mean pore size of 124 nm and overall porosity of 78.9%, the rejection of D. salina microalgae was as high as 93.2%. Continuous cultivation of D. salina in the helical photobioreactor at a dilution rate of 0.48 day−1 resulted in a biomass productivity (concentration) of 4.9 × 107 cells L−1 h−1 (2.7 × 106 cells mL−1). Interestingly, cultivation at the same initial dilution rate (0.48 day−1) in the helical photobioreactor coupled with the CRS resulted in a biomass productivity (concentration) of 9.3 × 107 cells L−1 h−1 (6.7 × 106 cells mL−1).ConclusionsThe results revealed the potential of the proposed system for enhancing biomass productivity by 90% and biomass concentration by more than twofold. The cultivation system is also proposed as a potential tool for cultivations in wastewaters. © 2019 Society of Chemical Industry