bluuebunny/crossref_metadata_2025 huggingface dataset:
The chemfp project
Authors: Dalke Andrew
Published: December 2019

The chemfp project has had four main goals: (1) promote the FPS format as a text-based exchange format for dense binary cheminformatics fingerprints, (2) develop a high-performance implementation of the BitBound algorithm that could be used as an effective baseline to benchmark new similarity search implementations, (3) experiment with funding a pure open source software project through commercial sales, and (4) publish the results and lessons learned as a guide for future implementors. The FPS format has had only minor success, though it did influence development of the FPB binary format, which is faster to load but more complex. Both are summarized. The chemfp benchmark and the no-cost/open source version of chemfp are proposed as a reference baseline to evaluate the effectiveness of other similarity search tools. They are used to evaluate the faster commercial version of chemfp, which can test 130 million 1024-bit fingerprint Tanimotos per second on a single core of a standard x86-64 server machine. When combined with the BitBound algorithm, a k = 1000 nearest-neighbor search of the 1.8 million 2048-bit Morgan fingerprints of ChEMBL 24 averages 27 ms/query. The same search of 970 million PubChem fingerprints averages 220 ms/query, making chemfp one of the fastest CPU-based similarity search implementations. Modern CPUs are fast enough that memory bandwidth and latency are now important factors. Single-threaded search uses most of the available memory bandwidth. Sorting the fingerprints by popcount improves memory coherency, which when combined with 4 OpenMP threads makes it possible to construct an N × N similarity matrix for 1 million fingerprints in about 30 min. These observations may affect the interpretation of previous publications which assumed that search was strongly CPU bound. The chemfp project funding came from selling a purely open-source software product. Several product business models were tried, but none proved sustainable. Some of the experiences are discussed, in order to contribute to the ongoing conversation on the role of open source software in cheminformatics.
Molecular characterization of a Trichinella spiralis enolase and its interaction with the host’s plasminogen
Authors: Jiang Peng , Zao You Jiao , Yan Shu Wei , Song Yan Yan , Yang Dong Min , Dai Li Yuan , Liu Ruo Dan , Zhang Xi , Wang Zhong Quan , Cui Jing
Published: December 2019

The binding and activation of host plasminogen (PLG) by worm surface enolases has been verified to participate in parasite invasion, but the role of this processes duringTrichinella spiralisinfection has not been clarified. Therefore, the expression and immunolocalization of aT. spiralisenolase (TsENO) and its binding activity with PLG were evaluated in this study. Based on the three-dimensional (3D) molecular model of TsENO, the protein interaction between TsENO and human PLG was analysed by the ZDOCK server. The interacting residues were identified after analysis of the protein–protein interface by bioinformatics techniques. The key interacting residues were confirmed by a series of experiments. The qPCR analysis results demonstrated that Ts-enowas transcribed throughout the whole life cycle ofT. spiralis. The immunofluorescence assay (IFA) results confirmed that TsENO was distributed on theT. spiralissurface. The binding assays showed that recombinant TsENO (rTsENO) and native TsENO were able to bind PLG. Four lysine residues (90, 289, 291 and 300) of TsENO were considered to be active residues for PLG interaction. The quadruple mutant (Lys90Ala + Lys289Ala + Lys291Ala + Lys300Ala) TsENO, in which the key lysine residues were substituted with alanine (Ala) residues, exhibited a reduction in PLG binding of nearly 50% (45.37%). These results revealed that TsENO has strong binding activity with human PLG. The four lysine residues (90, 289, 291 and 300) of TsENO play an important role in PLG binding and could accelerate PLG activation and invasion of the host’s intestinal wall byT. spiralis.
Effectiveness of physical activity promotion and exercise referral in primary care: protocol for a systematic review and meta-analysis of randomised controlled trials
Authors: Laake Jean-Pierre , Fleming Joanna
Published: December 2019

Background

Physical inactivity is the fourth leading risk factor for global mortality. Reducing sedentary behaviour and increasing physical activity are efficacious for improving many physical and mental health conditions including cardiovascular disease, type 2 diabetes and depression. Reducing sedentary behaviour and increasing physical activity can also be effective at reducing obesity; however, sedentary behaviour and reduced physical activity are also associated with mortality independently. Despite this, most adults in the UK do not currently meet the UK Chief Medical Officers’ guidelines for weekly physical activity. As most adults visit their general practitioner at least once a year, the primary care consultation provides a unique opportunity to deliver exercise referral or physical activity promotion interventions. This is a protocol for a systematic review of randomised controlled trials for the effectiveness of physical activity promotion and referral in primary care.

Methods

A comprehensive literature search of Embase, MEDLINE (Ovid), Web of Science (Core Collection), Scopus, CINAHL, PsycINFO, and The Cochrane Library (CENTRAL) will be conducted for studies with a minimum follow-up of 12 months that report physical activity as an outcome measure (by either self-report or objective measures) including an intention to treat analysis. The authors will screen papers, first by title and abstract and then by full text, independently assess studies for inclusion, appraise risk of bias and extract data. The quality of the evidence will be assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluations) approach. The primary outcome will be participation in physical activity at 12 months. Pooled effects will be calculated using random effects models. Results will be submitted for publication in a peer-reviewed journal and for presentation at UK national primary care conferences.

Discussion

This systematic review and meta-analyses will summarise the evidence for the effectiveness of physical activity promotion and referral as interventions for improving physical activity, as well as whether studies using objective measures of physical activity have similar effects to those studies using self-report measures. This knowledge has importance for primary care clinicians, patients and, given the focus of the recent NHS long-term plan on preventive medicine, those making policy decisions.

Systematic review registration

The protocol is registered with PROSPERO the international prospective register of systematic reviews, ID CRD42019130831
Antibiotic regimens for neonatal sepsis - a protocol for a systematic review with meta-analysis
Authors: Korang Steven Kwasi , Safi Sanam , Gluud Christian , Lausten-Thomsen Ulrik , Jakobsen Janus C.
Published: December 2019

Background

Sepsis is a major cause of morbidity and mortality among neonates and infants. Antibiotics are a central part of the first line treatment for sepsis in neonatal intensive care units worldwide. However, the evidence on the clinical effects of the commonly used antibiotic regimens for sepsis in neonates remains scarce. This systematic review aims to assess the efficacy and harms of antibiotic regimens for neonatal sepsis.

Methods

Electronic searches will be conducted in MEDLINE, Embase, The Cochrane Library, CINAHL, ZETOC and clinical trial registries (clinicaltrials.gov and ISRCTN). We will include randomised controlled trials of different antibiotic regimens for sepsis of neonates and infants. Eligible interventions will be any antibiotic regimen. Two reviewers will independently screen, select, and extract data. The methodological quality of individual studies will be appraised following Cochrane methodology. Primary outcomes will be ‘all-cause mortality’ and ‘serious adverse events’. Secondary outcomes will be ‘need for respiratory support’, ‘need for circulatory support’, ‘neurodevelopmental impairment’, ototoxicity, nephrotoxicity and necrotizing enterocolitis. We plan to perform a meta-analysis with trial sequential analysis.

Discussion

This is the study protocol for a systematic review on the effects of different antibiotic regimens for neonatal sepsis. The results of this systematic review intent to adequately inform stakeholders or health care professionals in the field of neonatal sepsis, and to aid appropriate development of treatment guidelines.

Systematic review registration

PROSPERO reference number: CRD42019134300.
Estimation for random coefficient integer-valued autoregressive model under random environment
Authors: Cui Yan , Wang Yun Y.
Published: December 2019

A first-order random coefficient integer-valued autoregressive model based on the negative binomial thinning operator under r states random environment is introduced. This paper derives numerical characteristics of the proposed model, establishes Yule–Walker estimators of model parameters, and discusses the strong consistency of the obtained estimators. Finally, a simulation is carried out to verify the feasibility of parameter estimation.
Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB
Authors: Al-Mutairi Noura M. , Ahmad Suhail , Mokaddas Eiman M.
Published: December 2019

Background

Increasing incidence of multidrug-resistantMycobacterium tuberculosisinfections is hampering global tuberculosis control efforts. Kuwait is a low-tuberculosis-incidence country, and ~ 1% ofM. tuberculosisstrains are resistant to rifampicin and isoniazid (MDR-TB). This study detected mutations in seven genes predicting resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin in MDR-TB strains. Sequence data were combined with spoligotypes for detecting local transmission of MDR-TB in Kuwait.

Methods

Ninety-three MDR-TB strains isolated from 12 Kuwaiti and 81 expatriate patients and 50 pansusceptible strains were used. Phenotypic drug susceptibility was determined by MGIT 460 TB/960 system. Mutations conferring resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin were detected by genotype MTBDRplusassay and/or PCR sequencing of threerpoBregions, katGcodon 315 (katG315) + inhAregulatory region,pncA, threeembBregions andrpsL + rrs-500–900 regions. Spoligotyping kit was used, spoligotypes were identified by SITVIT2, and phylogenetic tree was constructed by using MIRU-VNTRplus software. Phylogenetic tree was also constructed from concatenated sequences by MEGA7 software. Additional PCR sequencing ofgidBandrpsAwas performed for cluster isolates.

Results

Pansusceptible isolates contained wild-type sequences. Mutations inrpoBandkatGand/orinhAwere detected in 93/93 and 92/93 MDR-TB strains, respectively. Mutations were also detected for pyrazinamide resistance, ethambutol resistance and streptomycin resistance in MDR-TB isolates inpncA,embBandrpsL + rrs, respectively. Spoligotyping identified 35 patterns with 18 isolates exhibiting unique patterns while 75 isolates grouped in 17 patterns. Beijing genotype was most common (32/93), and 11 isolates showed nine orphan patterns. Phylogenetic analysis of concatenated sequences showed unique patterns for 51 isolates while 42 isolates grouped in 16 clusters. Interestingly, 22 isolates in eight clusters by both methods were isolated from TB patients typically within a span of 2 years. Five of eight clusters were confirmed by additionalgidBandrpsAsequence data.

Conclusions

Our study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified several potential clusters of local transmission of MDR-TB involving 2–6 subjects which had escaped detection by routine surveillance studies. Prospective detection of resistance-conferring mutations can identify possible cases of local transmission of MDR-TB in low MDR-TB settings.
Molecular biogeography of planktonic and benthic diatoms in the Yangtze River
Authors: Wang Jiawen , Liu Qingxiang , Zhao Xianfu , Borthwick Alistair G. L. , Liu Yuxin , Chen Qian , Ni Jinren
Published: December 2019

Background

Diatoms are of great significance to primary productivity in oceans, yet little is known about their biogeographic distribution in oligotrophic rivers.

Results

With the help of metabarcoding analysis of 279 samples from the Yangtze River, we provided the first integral biogeographic pattern of planktonic and benthic diatoms over a 6030 km continuum along the world’s third largest river. Our study revealed spatial dissimilarity of diatoms under varying landforms, including plateau, mountain, foothill, basin, foothill-mountain, and plain regions, from the river source to the estuary. Environmental drivers of diatom communities were interpreted in terms of photosynthetically active radiation, temperature, channel slope and nutrients, and human interference. Typical benthic diatoms, such as Pinnularia, Paralia, and Aulacoseira, experienced considerable reduction in relative abundance downstream of the Three Gorges Dam and the Xiluodu Dam, two of the world’s largest dams.

Conclusions

Our study revealed that benthic diatoms are of particular significance in characterizing motile guild in riverine environments, which provides insights into diatom biogeography and biogeochemical cycles in large river ecosystems.
EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway
Authors: Wu Jing , Yang Yi , He You , Li Qiang , Wang Xu , Sun Chengjun , Wang Lishun , An Yu , Luo Feihong
Published: December 2019

Background

Mandibulofacial dysostosis with microcephaly (MFDM) is characteristic of multiple skeletal anomalies comprising craniofacial anomalies/dysplasia, microcephaly, dysplastic ears, choanal atresia, and short stature. Heterozygous loss of function variants of EFTUD2 was previously reported in MFDM; however, the mechanism underlying EFTUD2-associated skeletal dysplasia remains unclear.

Results

We identified a novel frameshift variant of EFTUD2 (c.1030_1031delTG, p.Trp344fs*2) in an MFDM Chinese patient with craniofacial dysmorphism including ear canal structures and microcephaly, mild intellectual disability, and developmental delay. We generated a zebrafish model of eftud2 deficiency, and a consistent phenotype consisting of mandibular bone dysplasia and otolith loss was observed. We also showed that EFTUD2 deficiency significantly inhibited proliferation, differentiation, and maturation in human calvarial osteoblast (HCO) and human articular chondrocyte (HC-a) cells. RNA-Seq analysis uncovered activated TP53 signaling with increased phosphorylation of the TP53 protein and upregulation of five TP53 downstream target genes (FAS, STEAP3, CASP3, P21, and SESN1) both in HCO and in eftud2−/− zebrafish. Additionally, inhibition of p53 by morpholino significantly reduced the mortality of eftud2−/− larvae.

Conclusions

Our results confirm a novel de novo variant of the EFTUD2 gene and suggest that EFTUD2 may participate in the maturation and differentiation of osteoblasts and chondrocytes, possibly via activation of the TP53 signaling pathway. Thus, mutations in this gene may lead to skeletal anomalies in vertebrates.
Epidemiological pathology of Aβ deposition in the ageing brain in CFAS: addition of multiple Aβ-derived measures does not improve dementia assessment using logistic regression and machine learning approaches
Authors:   on behalf of the Cognitive Function and Ageing Neuropathology Study Group, Wharton S. B. , Wang D. , Parikh C. , Matthews F. E. , Brayne C. , Ince P. G.
Published: December 2019

Aβ-amyloid deposition is a key feature of Alzheimer’s disease, but Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment, based on neuritic plaque density, shows a limited relationships to dementia. Thal phase is based on a neuroanatomical hierarchy of Aβ-deposition, and in combination with Braak neurofibrillary tangle staging also allows derivation of primary age-related tauopathy (PART). We sought to determine whether Thal Aβ phase predicts dementia better than CERAD in a population-representative cohort (n = 186) derived from the Cognitive Function and Ageing Study (CFAS). Cerebral amyloid angiopathy (CAA) was quantitied as the number of neuroanatomical areas involved and cases meeting criteria for PART were defined to determine if they are a distinct pathological group within the ageing population. Agreement with the Thal scheme was excellent. In univariate analysis Thal phase performed less well as a predictor of dementia than CERAD, Braak or CAA. Logistic regression, decision tree and linear discriminant analysis were performed for multivariable analysis, with similar results. Thal phase did not provide a better explanation of dementia than CERAD, and there was no additional benefit to including more than one assessment of Aβ in the model. Number of areas involved by CAA was highly correlated with assessment based on a severity score (p < 0.001). The presence of capillary involvement (CAA type I) was associated with higher Thal phase and Braak stage (p < 0.001). CAA was not associated with microinfarcts (p = 0.1). Cases satisfying pathological criteria for PART were present at a frequency of 10.2% but were not older and did not have a higher likelihood of dementia than a comparison group of individuals with similar Braak stage but with more Aβ. They also did not have higher hippocampal-tau stage, although PART was weakly associated with increased presence of thorn-shaped astrocytes (p = 0.048), suggesting common age-related mechanisms. Thal phase is highly applicable in a population-representative setting and allows definition of pathological subgroups, such as PART. Thal phase, plaque density, and extent and type of CAA measure different aspects of Aβ pathology, but addition of more than one Aβ measure does not improve dementia prediction, probably because these variables are highly correlated. Machine learning predictions reveal the importance of combining neuropathological measurements for the assessment of dementia.
Thermotolerance evaluation of Taiwan Japonica type rice cultivars at the seedling stage
Authors: Hsuan Ta-Ping , Jhuang Pei-Rong , Wu Wen-Chin , Lur Huu-Sheng
Published: December 2019

Background

The subtropical rice varieties grown in Taiwan are mainly Japonica-type rice varieties, which are grown in the southernmost- and lowest-latitude Japonica type rice cultivation area in the world. In Taiwan, seedlings that are planted either by transplanting or direct seeding in the second crop will face the season with the highest temperatures during the year. High-temperature stress severely influences early rice growth and causes yield losses. With global warming deteriorating, this problem is becoming increasingly severe. This study attempted to establish a high-efficiency and time-saving screening tool for rice varieties that exhibit thermotolerance during the early growth stages and further identify good donors with better tolerance for high temperature stress from Taiwan Japonica type rice germplasm.

Results

During the initial germination stage, there were significantly different responses to heat stress among the different rice varieties. After the temperature induction response technique (TIR) treatment, the seedling survival rate and relative growth rate of the rice varieties under high temperature stress were significantly improved. In addition, the seedlings of the thermotolerant varieties demonstrated greater thermotolerance performance in the pot experiment as well as cell membrane stability (CMS) and cell activity (2,3,5-triphenyl-tetrazolium chloride; TTC) test results. However, the correlation between the thermotolerance of the seedlings and seeds was low. A phylogenetic dendrogram was plotted and revealed that thermotolerant genes did not concentrate in specific clusters. Furthermore, there was a non-significant correlation between the thermotolerance of the varieties and the years in which they were released.

Conclusions

The temperature induction screening tool established by this study could determine the potential of each variety to adapt to high temperature stress. Additionally, thermotolerance during different growth stages (i.e., the germination, seedling, and grain maturation stages) exhibited low correlations. In this study, the varieties obtained through preliminary screening (i.e., TK14, HC56, TT30, TNG70, and TK8) exhibited outstanding thermotolerance. The screen tools and thermotolerance varieties could be valuable resources for the countries that grow Japonica type rice to apply when breeding thermotolerant varieties in the future.
Source constraints for the 2015 phreatic eruption of Hakone volcano, Japan, based on geological analysis and resistivity structure
Authors: Mannen Kazutaka , Tanada Toshikazu , Jomori Akira , Akatsuka Takashi , Kikugawa George , Fukazawa Yui , Yamashita Hiroyuki , Fujimoto Koichiro
Published: December 2019

On June 29, 2015, a small phreatic eruption occurred in the most intensively steaming area of Hakone volcano, Japan. A previous magnetotelluric survey for the whole volcano revealed that the eruption center area (ECA) was located near the apex of a bell-shaped conductive body (resistivity < 10 Ωm) beneath the volcano. We performed local, high-resolution magnetotelluric surveys focusing on the ECA before and after the eruption. The results from these, combined with our geological analysis of samples obtained from a steam well (500 m deep) in the ECA, revealed that the conductive body contained smectite. Beneath the ECA, however, the conductive body intercalated a very local resistive body located at a depth of approximately 150 m. This resistive body is considered a vapor pocket. For the 2 months prior to eruption, a highly localized uplift of the ECA had been observed via satellite InSAR. The calculated depth of the inflation source was coincident with that of the vapor pocket, implying that enhanced vapor flux during the precursory unrest increased the porosity and vapor content in the vapor pocket. In fact, our magnetotelluric survey indicated that the vapor pocket became inflated after the eruption. The layer overlaying the vapor pocket was characterized by the formation of various altered minerals, and mineral precipitation within the veins and cracks in the layer was considered to have formed a self-sealing zone. From the mineral assemblage, we conclude that the product of the 2015 eruption originated from the self-sealing zone. The 2015 eruption is thus considered a rupture of the vapor pocket only 150 m below the surface. Even though the eruption appeared to have been triggered by the formation of a considerably deeper crack, as implied by the ground deformation, no geothermal fluid or rocks from significantly deeper than 150 m were erupted.
PD-L1 expression correlated with p53 expression in oral squamous cell carcinoma
Authors: Tojyo Itaru , Shintani Yukari , Nakanishi Takashi , Okamoto Kenjiro , Hiraishi Yukihiro , Fujita Shigeyuki , Enaka Mayu , Sato Fuyuki , Muragaki Yasuteru
Published: December 2019

Background

Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC.

Methods

A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17.

Results

The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression.

Conclusion

The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.
How to make urban freight transport by tram successful?
Authors: De Langhe Katrien , Meersman Hilde , Sys Christa , Van de Voorde Eddy , Vanelslander Thierry
Published: December 2019

Many national and international bodies, such as the European Commission, encourage the use of environment-friendly transport modes. Local and national authorities take more and more measures, for instance road pricing, loading/unloading spaces and low-emission zones, to prevent negative transport-related externalities in urban areas. Hence, transport and logistics operators consider alternative ways to deliver goods in urban areas by using electric vehicles, cargo bikes, inland vessels and rail transport. Which of these alternative modes is appropriate for which transport flow depends on multiple factors, including the available transport infrastructure, the goods volume, the measures taken by the authorities and the presence of congestion. This paper focuses on urban freight transport by tram and the conditions for a successful implementation. A successful implementation is defined as an implementation that is viable, i.e. the difference between the change of the costs and the change of the benefits exceeds a certain threshold value. The viability is studied from a business-economic and a socio-economic perspective for a dedicated freight tram, a freight wagon behind a passenger tram and the transport of parcels by a passenger tram. A viability model is developed, based on a social cost-benefit analysis. The working of this model is illustrated by applying it to the city of Antwerp. The main findings show that the use of a freight wagon attached to a passenger tram provides more potential than a dedicated freight tram. A courier taking the tram to deliver some parcels can be viable as well. For all three types of tram transport, the socio-economic benefits exceed the business-economic ones. Critical factors affecting the viability include the transported volume, the efficiency of the current road transport, the timing of the transport, the need for post-haulage and the operational costs of both road and rail.
Formulation, in-vitro and in-vivo pharmacokinetic evaluation of simvastatin nanostructured lipid carrier loaded transdermal drug delivery system
Authors: Brito Raj S , Chandrasekhar Kothapalli Bonnoth , Reddy Kesavan Bhaskar
Published: December 2019

Background

A simvastatin nanostructured lipid carrier loaded transdermal patch was developed to enhance the bioavailability and therapeutic effect.

Methods

Simvastatin NLC preparation was prepared by optimized hot homogenization technique and were characterized by particle size in nanometer, polydispersity index, zeta potential in millivolt, scanning electron microscopy, and entrapment efficiency by applying Box Behnken design utilizing multiple linear regression method.

Results

Chosen optimized NLC F7 formulation has particle size of 125.4 ± 2.66 nm, zeta potential of − 33.6 ± 2.42 mV, and PI of 0.480 ± 0.24. The NLC was loaded in transdermal patch by solvent evaporation method and evaluated for physical characteristics, drug content, skin permeation studies, and in-vivo pharmacokinetic studies in male albino Wistar rat. In-vivo pharmacokinetic studies in NLC loaded transdermal patch show an increase in AUC0-αin mg/ml when compared to marketed oral dosage form, which confirms the enhancement of bioavailability of simvastatin by NLC loaded transdermal patch.

Conclusions

From the data, it was concluded that drug-loaded NLC transdermal patch will be a promising drug delivery system for poorly bioavailable drugs.
Metabolic Effects of Oxytocin
Authors: McCormack Shana E , Blevins James E , Lawson Elizabeth A
Published: December 2019

There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic potential for metabolic disorders. In model systems, OXT promotes weight loss by decreasing energy intake. Pair-feeding studies suggest that OXT-induced weight loss may also be partly due to increased energy expenditure and/or lipolysis. In humans, OXT appears to modulate both homeostatic and reward-driven food intake, although the observed response depends on nutrient milieu (eg, obese vs. nonobese), clinical characteristics (eg, sex), and experimental paradigm. In animal models, OXT is anabolic to muscle and bone, which is consistent with OXT-induced weight loss occurring primarily via fat loss. In some human observational studies, circulating OXT concentrations are also positively associated with lean mass and bone mineral density. The impact of exogenous OXT on human obesity is the focus of ongoing investigation. Future randomized, placebo-controlled clinical trials in humans should include rigorous, standardized, and detailed assessments of adherence, adverse effects, pharmacokinetics/pharmacodynamics, and efficacy in the diverse populations that may benefit from OXT, in particular those in whom hypothalamic OXT signaling may be abnormal or impaired (eg, individuals with Sim1 deficiency, Prader–Willi syndrome, or craniopharyngioma). Future studies will also have the opportunity to investigate the characteristics of new OXT mimetic peptides and the obligation to consider long-term effects, especially when OXT is given to children and adolescents. (Endocrine Reviews XX: XX – XX, 2020)
The PAX-SIX-EYA-DACH network modulates GATA-FOG function in fly hematopoiesis and human erythropoiesis
Authors: Creed T. Michael , Baldeosingh Rajkumar , Eberly Christian L. , Schlee Caroline S. , Kim MinJung , Cutler Jevon A. , Pandey Akhilesh , Civin Curt I. , Fossett Nancy G. , Kingsbury Tami J.
Published: December 2019

The GATA and PAX-SIX-EYA-DACH transcriptional networks (PSEDNs) are essential for proper development across taxa. Here, we demonstrate novel PSEDN roles in vivo in Drosophila hematopoiesis and in human erythropoiesis in vitro. Using Drosophila genetics, we show that PSEDN members function with GATA to block lamellocyte differentiation and maintain the prohemocyte pool. Overexpression of human SIX1 stimulated erythroid differentiation of human erythroleukemia TF1 cells and primary hematopoietic stem-progenitor cells. Conversely, SIX1 knockout impaired erythropoiesis in both cell types. SIX1 stimulation of erythropoiesis required GATA1, as SIX1 overexpression failed to drive erythroid phenotypes and gene expression patterns in GATA1 knockout cells. SIX1 can associate with GATA1 and stimulate GATA1-mediated gene transcription, suggesting that SIX1-GATA1 physical interactions contribute to the observed functional interactions. In addition, both fly and human SIX proteins regulated GATA protein levels. Collectively, our findings demonstrate that SIX proteins enhance GATA function at multiple levels, and reveal evolutionarily conserved cooperation between the GATA and PSEDN networks that may regulate developmental processes beyond hematopoiesis.
Iron Oxide Nano-Particle Based Photochromic Composite Films
Authors: Miyazaki Hidetoshi , Yoshida Yusuke
Published: December 2019

Iron oxide (α-Fe2O3 and α-FeOOH)-based composite films were fabricated using an FeCl3·6H2O ethanol solution and transparent urethane resin. Iron oxide particles 50–90 nm in diameter were observed in the resulting composite films; analyses by Fourier transform infrared (FT-IR) spectroscopy and transmission electron microscopy confirmed the presence of iron oxide particles in the films. The films were initially yellowish-brown and turned greenish-gray upon UV irradiation. After UV irradiation of the films, their bandgap decreased (Bürstein–Moss effect). When the composite films (after UV irradiation) were placed in a dark room, their color and bandgap were restored to their initial states. Thus, the iron oxide-based composite films exhibited reversible photochromism.
Photons or protons for reirradiation in (non-)small cell lung cancer: Results of the multicentric ROCOCO in silico study
Authors: Troost Esther G.C. , Wink Krista C.J. , Roelofs Erik , Simone Charles B. , Makocki Sebastian , Löck Steffen , van Kollenburg Peter , Dechambre David , Minken Andre W.H. , van der Stoep Judith , Avery Stephen , Jansen Nicolas , Solberg Timothy , Bussink Johan , de Ruysscher Dirk
Published: December 2019

Objective:

Locally recurrent disease is of increasing concern in (non-)small cell lung cancer [(N)SCLC] patients. Local reirradiation with photons or particles may be of benefit to these patients. In this multicentre in silico trial performed within the Radiation Oncology Collaborative Comparison (ROCOCO) consortium, the doses to the target volumes and organs at risk (OARs) were compared when using several photon and proton techniques in patients with recurrent localised lung cancer scheduled to undergo reirradiation.

Methods:

24 consecutive patients with a second primary (N)SCLC or recurrent disease after curative-intent, standard fractionated radio(chemo)therapy were included in this study. The target volumes and OARs were centrally contoured and distributed to the participating ROCOCO sites. Remaining doses to the OARs were calculated on an individual patient’s basis. Treatment planning was performed by the participating site using the clinical treatment planning system and associated beam characteristics.

Results:

Treatment plans for all modalities (five photon and two proton plans per patient) were available for 22 patients (N = 154 plans). 3D-conformal photon therapy and double-scattered proton therapy delivered significantly lower doses to the target volumes. The highly conformal techniques, i.e., intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, TomoTherapy and intensity-modulated proton therapy (IMPT), reached the highest doses in the target volumes. Of these, IMPT was able to statistically significantly decrease the radiation doses to the OARs.

Conclusion:

Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. They, however, significantly differ in the dose deposited in the OARs. The therapeutic options, i.e., reirradiation or systemic therapy, need to be carefully weighed and discussed with the patients.

Advances in knowledge:

Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. In light of the abilities of the various highly conformal techniques to spare specific OARs, the therapeutic options need to be carefully weighed and patients included in the decision-making process.
Epitope mapping of an uncertain endogenous antigen implies secretogranin II peptide splicing
Authors: Howlett David R. , Clarke Iain J. , Newton Russell P. , Hart John E.
Published: December 2019

Background: The search for a tissue-mass reducing reproductive hormone involved a bioassay-guided physicochemical fractionation of sheep blood plasma. This brought forth a candidate protein whose apparent mass on gels and in mass spectrometry (MS) was 7-8 kDa, implying a polypeptide of ~70 residues. Four purification runs gave Edman N-terminal sequences relating to 1MKPLTGKVKEFNNI14. This is bioinformatically obscure and has been resistant to molecular biological investigation. The sequence was synthesized as the peptide EPL001, against which was raised a goat polyclonal antiserum, G530. Used in an antigen capture campaign, G530 pointed to the existence of a novel derivative of secretogranin II (SgII), the neuroendocrine secretory vesicle helper protein and prohormone. The proposed SgII derivative was dubbed SgII-70, yet the sequence commonality between SgII and EPL001 is essentially NNI.

Methods: Immunohistochemical (IHC) labelling with G530 is reported within rat, mouse and human cerebrovasculature and in glandular elements of the mouse intestine. Epitope mapping involved IHC peptide preabsorption, allied to deductive bioinformatics and molecular modelling in silico.

Results: G530 is deemed monoepitopic in regard to both its synthetic antigen (EPL001) and its putative endogenous antigen (SgII related). The epitope within EPL001 of the anti-EPL001 antibody is inferred to be the contiguous C-terminal 9KEFNNI14. This is so because the G530 blockade data are consistent with the epitope in the mammalian endogenous antigen being part contiguous, part non-contiguous KE·F·NNI, ex hypothesi. The observed immunostaining is deduced to be due to pre-SgII-70, which has a non-C-terminal NNI, and SgII-70, which has an N-terminal MLKTGEKPV/N and a C-terminal NNI (these two motifs being in the reverse order in the SgII parent protein).

Conclusion: The present data are consistent with the hypothesis that the anti-EPL001 antibody binds to an SgII-related epitope. SgII is apparently subject to peptide splicing, as has been reported for the related chromogranin A.
Recent advances in understanding and managing malabsorption: focus on microvillus inclusion disease
Authors: Jayawardena Dulari , Alrefai Waddah A. , Dudeja Pradeep K. , Gill Ravinder K.
Published: December 2019

Microvillus inclusion disease (MVID) is a rare congenital severe malabsorptive and secretory diarrheal disease characterized by blunted or absent microvilli with accumulation of secretory granules and inclusion bodies in enterocytes. The typical clinical presentation of the disease is severe chronic diarrhea that rapidly leads to dehydration and metabolic acidosis. Despite significant advances in our understanding of the causative factors, to date, no curative therapy for MVID and associated diarrhea exists. Prognosis mainly relies on life-long total parenteral nutrition (TPN) and eventual small bowel and/or liver transplantation. Both TPN and intestinal transplantation are challenging and present with many side effects. A breakthrough in the understanding of MVID emanated from seminal findings revealing mutations inMYO5Bas a cause for MVID. During the last decade, many studies have thus utilized cell lines and animal models with knockdown ofMYO5Bto closely recapitulate the human disease and investigate potential therapeutic options in disease management. We will review the most recent advances made in the research pertaining to MVID. We will also highlight the tools and models developed that can be utilized for basic and applied research to increase our understanding of MVID and develop novel and effective targeted therapies.
Energy Efficient Routing Protocol for Mobile Social Sensing Networks
Authors: Sati Salem , Sohoud Ahmed , Abulifa Tareg
Published: December 2019

Mobile Social Sensing Network (MSSN) is a subclass of Wireless Sensor Networks (WSN). This MSSN is consists of mobile sensing transducers carried by people. Sensing information gathered by mobile sensors will transmit to the data sink. This data sink may it is fixed or mobile. But in optimal cases, it should have efficient energy and position compared with other mobile sensors. On the other hand, mobile sensors may have a social tie because they carried by people. Traditional MANET routing protocols such as AODV and DSR are inapplicable or perform poorly for mobile social data sensing. Especially for distributed mobile social sensing. Insufficient performance due to the nature of the mobile sensors which suffering from a limited energy source. In recent days, there are many routing protocols proposed by researchers. These protocols improve the total delivered messagesin mobile social sensing networks, but most of them do not take into account the link bandwidth and node storage limitation, thus routing may lead to more energy consumption among mobile sensing nodes. In this paper, we design an Energy-Efficient Routing Protocol (EERP) for mobile social sensing networks. We consider the node energy as a balance function between the delay of collected data and transmission of sensor nodes to the data sink. Furthermore, we also develop an enhanced version of the suggested EERP which named EERP+S, EERP+S combines the energy percentage and social metric of node degree. EERP and its updated version EERP+S are dynamically adjusting the control function based on data delay and transmission in addition to node activity. Simulation results demonstrate the efficiency of EERP and EERP+S compared with the flooding behavior of an Epidemic. Epidemic and its social version Ep-Soc are compared with suggested protocols in distributed mobile social sensing paradigms.
Civil right. Special part
Authors: Шаповал Ольга , Shapoval Olga , Романова Елизавета , Romanova Elizaveta
Published: December 2019

Civil law is one of the basic law disciplines. Traditionally this discipline is divided into General and Special parts.
The book is a summary of the course of Special part of civil law, covers all topics of the discipline which is taught at the law faculties of higher educational institutions. The textbook's structure reflects the system of structure of chapters and sections of the civil code of Russian Federation.
The textbook is intended for teachers and students of law faculties studying the discipline "Civil law".
A Dynamic Model of Embeddedness in Digital Infrastructures
Authors: Fürstenau Daniel , Baiyere Abayomi , Kliewer Natalia
Published: December 2019

Digital infrastructures result from individual yet interdependent systems evolving in relation to each other. This paper identifies three processes by which individual systems become embedded into digital infrastructures. The first is a parallel process, whereby systems become embedded independently of each other. The second is a competitive process, whereby systems compete for resources and attention and one system usually thrives while the other system loses importance. The third is a spanning process characterizing a situation of boundary-spanning between distinct parts of a digital infrastructure. The three processes, synthesized into a dynamic model of digital infrastructure embeddedness, offer clarity to the question how digital infrastructures evolve. They also provide insight into the emergence of three forms of digital infrastructures: silofied, regenerated, and unified. Reflecting an interconnection view, our research further facilitates an understanding of infrastructure inertia and its associated consequence. Criticality traps should be avoided by considering the right timing for system replacement in the light of growing embeddedness over time.
“Monday Effect” on Performance Variations in Supply Chain Fulfillment: How Information Technology–Enabled Procurement May Help
Authors: Yao Yuliang , Dresner Martin , Zhu Kevin Xiaoguo
Published: December 2019

If labor productivity varies in unknown ways over time, this could lead to unforeseen fluctuations in production or delivery rates, leading to stockouts or inventory build-up in a supply chain, while contributing to higher operating costs and to lower satisfaction levels for customers. The “Monday Effect,” that is lower productivity and higher error rates on Mondays compared with other days of the week, has been demonstrated in the finance and industrial relations literature. Using a database of 12 months of purchases from the General Services Administration (GSA) of the U.S. government (a key distributor of goods to government purchasers), we show that, indeed, performance is lower on Mondays compared with other weekdays in terms of order fulfillment and order cycle time. However, when purchasers use the GSA’s internet-based electronic market instead of using manual ordering procedures, the fulfillment gap between Mondays and other weekdays narrows considerably, demonstrating the value of information technology in smoothing distribution flows. By acknowledging the Monday Effect, distributors can thus plan for these weekly fluctuations and use information technology to improve service levels.
Migration percentage and odds of recurrence/subsequent surgery after treatment for hip subluxation in pediatric cerebral palsy: A meta-analysis and systematic review
Authors: Agarwal K. N. , Chen C. , Scher D. M. , Dodwell E. R.
Published: December 2019

Purpose

This meta-analysis aims to systematically assess and quantitatively pool the best clinical evidence for migration percentage (MP) and odds ratio (OR) for recurrence/reoperation following treatment for hip subluxation in children with cerebral palsy (CP), including Botulinum Toxin A (BNT-A), soft-tissue lengthening and osteotomies

Methods

Pubmed, EMBASE and Cochrane were systematically searched from between 1 January 1953 and 11 January 2017 inclusive for studies reporting resubluxation/reoperation rates, and/or MP following treatment for hip subluxation in children with CP. The primary outcome was odds of resubluxation/reoperation. The secondary outcome was change in MP. Studies were graded for quality using the Newcastle Ottawa Scale. This meta-analysis was performed and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results

A total of 14 studies were included in analysis of odds of resubluxation/reoperation and 24 studies were included in analysis of MP. The OR for resubluxation/reoperation was lower for combined osteotomies compared with femoral (OR = 0.49; 95% confidence interval (CI) 0.25 to 0.98) and for femoral osteotomy compared to soft-tissue procedures (OR = 0.20; 95% CI 0.07 to 0.61). There was no difference in odds of recurrence/reoperation between pelvic and femoral osteotomies (OR = 2.27; 95% CI 0.37 to 13.88). Combined osteotomies provided the greatest improvement in MP, while BoNT-A showed no improvement in MP.

Conclusion

Resubluxation/reoperation rates are high; management with osteotomies is preferred to soft-tissue procedures alone in preventing resubluxation/reoperation. This meta-analysis is limited by the observational nature and small sample sizes of many of the included studies, with their inherent risk of bias and lack of homogeneity of patient characteristics at baseline. It is possible that with larger and higher quality studies, the results and conclusions of this analysis may be altered.