bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection
Authors: Pease Christopher , Hutton Brian , Yazdi Fatemeh , Wolfe Dianna , Hamel Candyce , Barbeau Pauline , Skidmore Becky , Alvarez Gonzalo G. 
Published: March 2018

AbstractPurposeTuberculosis (TB) remains a common cause of death globally. A regimen of 12 doses of isoniazid (INH) and rifapentine given once weekly (INH/RPT‐3) has recently been recommended by the World Health Organization for the treatment of latent TB infection (LTBI). We aimed to determine whether the INH/RPT‐3 regimen had similar or lesser rates of adverse events compared to other LTBI regimens, namely INH for 9 months, INH for 6 months, rifampin for 3 to 4 months, and rifampin plus INH for 3 to 4 months.MethodsWe searched MEDLINE, Embase, CENTRAL, PubMed, ICTRP, clinicaltrials.gov, and Canadian Agency for Drugs and Technologies in Health's Gray Matters Light for randomized, postmarketing, and comparative nonrandomized studies of patients with confirmed LTBI that reported the frequency of at least 1 adverse event of relevance for a regimen of interest. The search included studies published until March 2017. The frequencies of adverse events were extracted and are presented descriptively.ResultsData from 23 randomized and 55 nonrandomized studies were included. Although inconsistent event reporting and high heterogeneity limited comparisons, the adverse event profile of INH/RPT‐3 appeared generally favorable. Flu‐like reactions were reported with an increased frequency and hepatotoxicity with a lower frequency than standard treatment.ConclusionsWhile INH/RPT‐3 had an overall low frequency of adverse events compared to INH monotherapy, reporting of adverse events for many regimens was limited meaning results should be interpreted cautiously. Future studies of LTBI treatment would benefit from more complete collection and reporting of adverse events and more consistent definitions of hepatotoxicity.
Converting polar cyclic peptides into membrane permeable molecules using N‐methylation
Authors: Lee Leo L. H. , Buckton Laura K. , McAlpine Shelli R. 
Published: March 2018

AbstractDescribed are the design, synthesis, and biological evaluation of 5 N‐methylated analogs that are based on a lead drug structure LB51. LB51 is a cyclic pentapeptide that inhibits heat shock protein 90 and although a potent inhibitor of the protein function, it has poor cell permeability. Introduction of an N‐methyl moiety at each amino acid produces 5 analogs of LB51, where all 5 show significantly improved membrane permeability over the lead molecule despite the presence of 4 highly polar side chains.
On the use of acrylated epoxidized soybean oil as a reactive compatibilizer in injection‐molded compostable pieces consisting of polylactide filled with orange peel flour
Authors: Quiles‐Carrillo Luis , Montanes Nestor , Lagaron Jose Maria , Balart Rafael , Torres‐Giner Sergio 
Published: March 2018

AbstractNovel green composites made of polylactide (PLA) and orange peel flour (OPF) were melt‐compounded using twin‐screw extrusion and shaped into pieces by injection molding. Orange peel, a major by‐product of the juice industry, was first ground to flour and then incorporated as a lignocellulosic filler into the biopolymer at 10, 20 and 30 wt%. Since both components of the green composite presented low compatibility, the resultant injection‐molded pieces showed poor ductility and impaired thermomechanical performance. As a new bio‐based reactive compatibilizer, acrylated epoxidized soybean oil (AESO) was added at five parts per hundred resin to the PLA/OPF formulations during the extrusion process. The addition of AESO increased the filler–biopolymer adhesion and led to compostable green composite pieces with improved physical properties. The enhancement achieved was related to a dual effect of plasticization and melt grafting of the OPF particles onto the PLA chains provided by the multiple acrylate and epoxy groups present in AESO. The use of multi‐functionalized vegetable oils to improve the performance of green composites certainly opens up new opportunities for the expansion of fully bio‐based and biodegradable materials that are partially obtained from agro‐food waste. © 2018 Society of Chemical Industry
Preparation of composites based on recycled polypropylene and automotive shredder residue
Authors: Yang Shuangqiao , Bai Shibing , Duan Wenfeng , Wang Qi 
Published: March 2018

AbstractIn past research, mechanical recycling of automotive shredder residue (ASR) has led to serious deterioration of material performance, and real‐scale application in this way still remains a challenge. Here, we report a sustainable approach called solid‐state shear milling (SSSM) for the production of high‐performance polypropylene (PP)/ASR composites with robust mechanical performance on a commercial scale. After the SSSM process, the obtained 50/50 wt% PP/ASR composite exhibited a 41.3% increase in tensile strength, 32.9% increase in flexural strength and 55.0% increase in impact toughness when compared with corresponding composites made by traditional direct melt blending. In particular, the toughness of the material can be improved by further addition of PP grafted with maleic anhydride with toughness comparable to that of recycled PP, and a 325% increase in toughness can be obtained with addition of styrene–butadiene–styrene block copolymer grafted with maleic anhydride. This PP/ASR composite shows good processability and high thermal stability, and meets the requirements of many applications for nonstructural products. The approach presented in this paper highlights a novel technique for ASR recycling. © 2018 Society of Chemical Industry
Self‐propagating amplification reactions for molecular detection and signal amplification: Advantages, pitfalls, and challenges
Authors: Sun Xiaolong , Shabat Doron , Phillips Scott T. , Anslyn Eric V. 
Published: March 2018

AbstractSelf‐propagating cascade reactions are a recent development for chemosensing protocols. These cascade reactions, in principle, offer low limits of detection by virtue of exponential signal amplification and are initiated by a specific, preplanned molecular detection event. This combination of selectivity for a detection event followed by in situ signal amplification is achieved by exploitation of mechanistic organic chemistry and thus has resulted in various chemosensing protocols that use one or more reagents to achieve the desired selectivity and sensitivity for an assay. Species such as hydrogen peroxide, thiols, and fluoride have been used as active reagents to initiate the first examples of self‐propagating signal amplification reactions, although many other active reagents should be compatible with the approaches. A common feature of the reagents that support the self‐propagating signal amplification reactions is the involvement of quinone methide intermediates resulting from elimination of optical reporters and/or active reagents, where the latter propagates the signal amplification reaction. The early examples of these amplification sequences, however, are slow to reach full signal, thus leaving time for background reactions to generate nonspecific signals. This issue of background has limited practical applications of these self‐propagating signal amplification reactions, as has challenging synthetic routes to the reagents, as well as the potential for other chemical species to interfere with the detection and signal amplification processes. Thus, the goal of this review is to summarize the progress of self‐propagating signal amplification technology, to identify the pitfalls of current designs, and by doing so, to stimulate future studies in this growing and promising research area.
Tetrasubstituted bisadamantylidenes—Highly twisted alkenes
Authors: Bachrach Steven M. 
Published: March 2018

AbstractA number of 1,3,1′,3′‐tetrasubstituted bisadamantylidenes are examined with 4 different density functional methods (BP86‐D3, ωB97X‐D, B3LYP, and B3LYP‐D3) and the 6‐311G(d) basis set. With increasing steric bulk, these substituted bisadamantylidenes become ever more twisted about the central carbon‐carbon double bond. This manifests in significantly reduced singlet‐triplet gaps from that of typical alkenes, with the tetra‐t‐butylbisadamantylidene 17, twisted to almost 90°, having a gap of only 2.2 kcal mol−1. While its large strain energy may preclude the synthesis of 17, other less‐strained tetrasubstituted analogues are more feasible synthetic targets and still possess small singlet‐triplet gaps, which should be testable by variable temperature NMR and EPR spectroscopy. The twisted alkenes also result in a low rotational energy barrier, and 4 examples with a low barrier to cis‐trans isomerization are presented. These too should be testable by experiment.
Identification of Clostridium difficile Immunoreactive Spore Proteins of the Epidemic Strain R20291
Authors: Pizarro‐Guajardo Marjorie , Ravanal María Cristina , Paez Maria Daniela , Callegari Eduardo , Paredes‐Sabja Daniel 
Published: March 2018

PurposeClostridium difficile infections are the leading cause of diarrhea associated with the use of antibiotics. During infection, C. difficile initiates a sporulation cycle leading to the persistence of C. difficile spores in the host and disease dissemination. The development of vaccine and passive immunization therapies against C. difficile has focused on toxins A and B. In this study, an immunoproteome‐based approach to identify immunogenic proteins located on the outer layers of C. difficile spores as potential candidates for the development of immunotherapy and/or diagnostic methods against this devastating infection is used.Experimental designTo identify potential immunogenic proteins on the surface of C. difficile R20291, spore coat/exosporium extracts are separated by 2D electrophoresis (2‐DE) and analyzed for reactivity against C. difficile spore‐specific goat sera. Finally, the selected spots are in‐gel digested with chymotrypsin, peptides generated are separated by nanoUPLC followed by MS/MS using Quad‐TOF‐MS, corroborated by Ultimate 3000RS‐nano‐UHPLC coupled to Q‐Exactive‐Plus‐Orbitrap MS.ResultsThe analysis identify five immunoreactive proteins: spore coat proteins CotE, CotA, and CotCB; exosporium protein CdeC; and a cytosolic methyltransferase.ConclusionThis data provides a list of spore surface protein candidates as antigens for vaccine development against C. difficile infections.
2‐fluoro‐5‐maleimidobenzoic acid‐linked albumin drug (MAD) delivery for selective systemic targeting of metastatic prostate cancer
Authors: Akinboye Emmanuel S. , Rogers Oliver C. , Isaacs John T. 
Published: March 2018

BackgroundThe SH‐group at Cys‐34 of human serum albumin (HSA) is a unique and accessible functional group that can be exploited for efficient linkage of a maleimide containing cytotoxic drug derivative to albumin. The specific maleimide chemistry used for production of the maleimide‐linked albumin drug (MAD) is critical, however, to minimize the plasma concentration of “free” cytotoxic drug spontaneously released from albumin carrier thus decreasing dose‐limiting host toxicity while enhancing the plasma half‐life from minutes to days (ie, pharmacokinetic effect) and tissue concentration of the MAD in the extracellular cellular fluid at sites of cancer (ie, EPR effect).MethodsTo accomplish this goal, a chemical synthesis was developed using 2‐fluoro‐5‐maleimidobenzoic acid to stably link the potent cytotoxic chemically modified analogue of the naturally occurring sesquiterpene γ‐lactone, thapsigargin, 8‐O‐(12‐aminododecanoyl)‐8‐O‐debutanoyl thapsigargin (12ADT), to Cys‐34 of albumin to produce 12ADT‐MAD.ResultsUsing FITC‐labeling, LC/MS analysis, and in vitro growth and clonogenic survival assays on a series of 6 human prostate cancer lines (LNCaP, LAPC‐4, VCap, CWR22Rv1, PC3, and Du145), we documented that 12ADT‐MAD is endocytosed by prostate cancer cells where it is degraded into its amino acids liberating cysteinyl‐maleimide‐12ADT which is both chemically stable at the acidic pH of 5.5 present in the endosome while retaining its high killing ability (IC50 50 nM) via SERCA inhibition.ConclusionsBased upon these positive in vitro validation results, the in vivo efficacy versus host toxicity of this 12‐ADT‐MAD approach is presently being evaluated against a series of patient derived androgen responsive and castration resistant human xenografts in immune‐deficient mice.
A novel mouse model of human prostate cancer to study intraprostatic tumor growth and the development of lymph node metastases
Authors: Linxweiler Johannes , Körbel Christina , Müller Andreas , Hammer Markus , Veith Christian , Bohle Rainer M. , Stöckle Michael , Junker Kerstin , Menger Michael D. , Saar Matthias 
Published: March 2018

BackgroundIn this study, we aimed to establish a versatile in vivo model of prostate cancer, which adequately mimics intraprostatic tumor growth, and the natural routes of metastatic spread. In addition, we analyzed the capability of high‐resolution ultrasonography (hrUS), in vivo micro‐CT (μCT), and 9.4T MRI to monitor tumor growth and the development of lymph node metastases.MethodsA total of 5 × 105 VCaP cells or 5 × 105 cells of LuCaP136‐ or LuCaP147 spheroids were injected into the prostate of male CB17‐SCID mice (n = 8 for each cell type). During 12 weeks of follow‐up, orthotopic tumor growth, and metastatic spread were monitored by repetitive serum‐PSA measurements and imaging studies including hrUS, μCT, and 9.4T MRI. At autopsy, primary tumors and metastases were harvested and examined by histology and immunohistochemistry (CK5, CK8, AMACR, AR, Ki67, ERG, and PSA). From imaging results and PSA‐measurements, tumor volume doubling time, tumor‐specific growth rate, and PSA‐density were calculated.ResultsAll 24 mice developed orthotopic tumors. The tumor growth could be reliably monitored by a combination of hrUS, μCT, MRI, and serum‐PSA measurements. In most animals, lymph node metastases could be detected after 12 weeks, which could also be well visualized by hrUS, and MRI. Immunohistochemistry showed positive signals for CK8, AMACR, and AR in all xenograft types. CK5 was negative in VCaP‐ and focally positive in LuCaP136‐ and LuCaP147‐xenografts. ERG was positive in VCaP‐ and negative in LuCaP136‐ and LuCaP147‐xenografts. Tumor volume doubling times and tumor‐specific growth rates were 21.2 days and 3.9 %/day for VCaP‐, 27.6 days and 3.1 %/day for LuCaP136‐ and 16.2 days and 4.5 %/day for LuCaP147‐xenografts, respectively. PSA‐densities were 433.9 ng/mL per milliliter tumor for VCaP‐, 6.5 ng/mL per milliliter tumor for LuCaP136‐, and 11.2 ng/mL per milliliter tumor for LuCaP147‐xenografts.ConclusionsBy using different monolayer and 3D spheroid cell cultures in an orthotopic xenograft model, we established an innovative, versatile in vivo model of prostate cancer, which enables the study of both intraprostatic tumor growth as well as metastatic spread to regional lymph nodes. HrUS and MRI are feasible tools to monitor tumor growth and the development of lymph node metastases while these cannot be visualized by μCT.
The spatial distribution and temporal variability of föhn winds over the Larsen C ice shelf, Antarctica
Authors: Turton Jenny V. , Kirchgaessner Amelie , Ross Andrew N. , King John C. 
Published: March 2018

The eastern side of the Antarctic Peninsula (AP) mountain range and the adjacent ice shelves are frequently affected by föhn winds originating from upwind of the mountains. Six automatic weather stations (AWSs) and archived model output from 5 km resolution Antarctic Mesoscale Prediction System (AMPS) forecasts have been combined to identify the occurrence of föhn conditions, and their spatial distribution over the Larsen C Ice Shelf (LCIS) from 2009 to 2012.Algorithms for semi‐automatic detection of föhn conditions have been developed for both AWS and AMPS data. The frequency of föhn varies by location, being most frequent at the foot of the AP and in the north of the ice shelf. They are most common in spring, when they can prevail for 50% of the time. The results of this study have important implications for further research, investigating the impact of föhn on surface melting, and the surface energy budget of the ice shelf. This is of particular interest due to the collapse of Larsen A and B ice shelves in 1995 and 2002 respectively, and the potential instability issues following a large calving event on Larsen C in 2017.
In situ organic compound analysis on a meteorite surface by desorption electrospray ionization coupled with an Orbitrap mass spectrometer
Authors: Naraoka Hiroshi , Hashiguchi Minako 
Published: March 2018

RationaleSince extraterrestrial organic matter in meteorites is a very complex mixture that is hard to ionize due to its association with minerals, in situ analysis of polar organic compounds has never been performed. In addition, when studying powdered samples, spatial information of organic compounds is lost.MethodsIn situ molecular analysis and chemical imaging of polar organic compounds were performed on a meteorite surface by desorption electrospray ionization coupled with high‐resolution mass spectrometry (DESI‐HRMS) using an Orbitrap mass spectrometer.ResultsMany CHN compounds, including alkylated pyridine and imidazole homologues, were identified from the complex peaks by HRMS using a spray of electrically charged methanol with a spatial resolution of approximately 50 μm. The same alkylated homologues have the same spatial distribution in the meteorite matrix, while alkylpyridines occur in a different location from alkylimidazoles.ConclusionsThe compound distribution suggests a different source for each compound series or a chromatographic separation effect associated with fluid movement in the meteorite parent body. The DESI‐HRMS imaging will further our understanding of organic compound distribution with respect to mineral and water interactions in meteorites.
Axonal regeneration in zebrafish spinal cord
Authors: Ghosh Sukla , Hui Subhra Prakash 
Published: March 2018

AbstractIn the present review we discuss two interrelated events—axonal damage and repair—known to occur after spinal cord injury (SCI) in the zebrafish. Adult zebrafish are capable of regenerating axonal tracts and can restore full functionality after SCI. Unlike fish, axon regeneration in the adult mammalian central nervous system is extremely limited. As a consequence of an injury there is very little repair of disengaged axons and therefore functional deficit persists after SCI in adult mammals. In contrast, peripheral nervous system axons readily regenerate following injury and hence allow functional recovery both in mammals and fish. A better mechanistic understanding of these three scenarios could provide a more comprehensive insight into the success or failure of axonal regeneration after SCI. This review summarizes the present understanding of the cellular and molecular basis of axonal regeneration, in both the peripheral nervous system and the central nervous system, and large scale gene expression analysis is used to focus on different events during regeneration. The discovery and identification of genes involved in zebrafish spinal cord regeneration and subsequent functional experimentation will provide more insight into the endogenous mechanism of myelination and remyelination. Furthermore, precise knowledge of the mechanism underlying the extraordinary axonal regeneration process in zebrafish will also allow us to unravel the potential therapeutic strategies to be implemented for enhancing regrowth and remyelination of axons in mammals.
Association of genetic variants of PD1 with recurrent pregnancy loss
Authors: Hayashi Yuko , Nishiyama Takeshi , Nakatochi Masahiro , Suzuki Shugo , Takahashi Satoru , Sugiura‐Ogasawara Mayumi 
Published: March 2018

AbstractPurposeProgrammed cell death 1 (PD1) and PD ligand 1 (PDL1) are speculated to have an important role in maintaining a normal pregnancy and there are also a few reports of an association between the single‐nucleotide polymorphisms (SNPs) of PD1 or PDL1 and diseases in humans. The association was examined between the polymorphisms of PD1, PDL1, CTLA4 and recurrent pregnancy loss (RPL).MethodsThe study group consisted of 243 women with two or more pregnancy losses and 176 parous women. The frequency of three SNPs of PD1, two of PDL1, and four of CTLA4 were compared between the patients and controls. Next, the subsequent live birth rates in the patients with RPL with and without risk alleles were examined.ResultsTwo SNPs (rs36084323 and rs3481962) of PD1 were found to occur at significantly higher frequencies in the patient group than in the control group. The subsequent live birth rate of the patients with vs. without the risk alleles of rs36084323 and rs3481962 were 83.3% vs. 83.3% and 81.6% vs. 84.0%, respectively.ConclusionVariations of the PD1 gene were identified as risk factors for RPL. However, the presence or absence of the PD1 risk alleles had no predictive effect on the subsequent pregnancy outcome.
Resilience of riparian vegetation after restoration measures on River Inn
Authors: Bauer M. , Harzer R. , Strobl K. , Kollmann J. 
Published: March 2018

AbstractRiver restoration is widely applied, although its effects are poorly understood, and degraded habitats might be difficult to improve. Moreover, there is a lack of monitoring as well as few systematic comparisons of restoration methods. This study presents results of a 4‐year monitoring on River Inn (southern Germany) investigating restoration by gravel or sand addition or embankment removal. The results were compared with reference sites that represent the pre‐restoration conditions. At the landscape scale, we analysed vegetation types based on aerial photographs, whereas at a smaller scale, we undertook vegetation surveys and evaluated species composition, growth, and life form, as well as the proportion of the target vegetation. After 4 years, the data indicated a “negative resilience” of the vegetation back to the state prior to restoration. The structural analysis revealed an extensive spread of reed at expense of bare soil. Thus, the species composition largely regressed to the pre‐restoration conditions, and neither annuals nor other pioneer species showed a long‐term benefit of river restoration. There were differences among the three restoration treatments after 2 years, but no longer after 4 years. However, the river restoration had three positive outcomes: (a) There was a temporary benefit for pioneer vegetation that most likely replenished the seed bank of the respective species, (b) the valuable reed communities showed resilience, and (c) the measures allowed some practical learning as expected for adaptive restoration.
Catchment characteristics predicting nitrogen and phosphorus losses in Finland
Authors: Röman E. , Ekholm P. , Tattari S. , Koskiaho J. , Kotamäki N. 
Published: March 2018

AbstractEmpirical relationships between catchment properties and nutrient losses are often derived from spatially restricted data, which hampers the ability to more widely generalize the results. In this study, we regressed the catchment characteristics and the losses of total nitrogen (TN) and total phosphorus (TP) for all monitored catchments in Finland with adequate data (n = 59, from the year 2000 to 2011). TN loss was found to increase with the percentage of arable land and amount of point source loading and to decrease with increasing lake percentage. TP loss also increased not only with the percentage of arable land but also with fine‐grained soils (Cambisols) in the catchment and decreased with the percentage of lakes. Urban areas, scattered settlements, and N deposition were not significant explanatory variables, possibly due to their spatial covariation with arable land in Finland. Despite the fact that only a few significant explanatory variables were identified, the models explained the TN and TP losses by up to 91% and 92%, respectively.