bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Inflammatory Protein Profiles Distinguish Irritable Bowel Syndrome (IBS) and Ulcerative Colitis, Irrespective of Inflammation or IBS-Like Symptoms
Authors: Moraes Luiza , Magnusson Maria K , Mavroudis Georgios , Polster Annikka , Jonefjäll Börje , Törnblom Hans , Sundin Johanna , Simrén Magnus , Strid Hans , Öhman Lena
Published: January 2020

Background

Inflammatory mechanisms of ulcerative colitis (UC) and irritable bowel syndrome (IBS) may overlap or are part of different spectrums. However, potential links between inflammation and IBS-like symptoms in these patient groups are still unclear. The aim of this study was to determine if the systemic inflammatory protein (SIP) profiles differ between UC patients, with presence of inflammation or in remission with or without IBS-like symptoms, and IBS patients.

Methods

Serum from patients with active UC (UCA), UC patients in remission with or without IBS-like symptoms (UCR + IBS, UCR-IBS), IBS patients (IBS), and healthy subjects (HS) was analyzed using the ProSeek Multiplex Inflammation kit, which detects 92 proteins.

Results

The exploratory cohort consisted of 166 subjects (UCA, n = 40; UCR-IBS, n = 45; UCR + IBS, n = 20; IBS, n = 40; HS, n = 21). Systemic inflammatory protein profiles separated UC from non-UC (HS and IBS) patients in multivariate analysis, revealing caspase 8, axin 1, sulfotransferase 1A1, and tumor necrosis factor superfamily member 14 as the variables most important to clustering. Although minor differences were detected between UCR + IBS and UCR-IBS, SIP profiles discriminated UCA from UCR, and interleukin (IL) 17C, IL17A, chemokine ligand 9, and transforming growth factor–α characterized active inflammation. SIP profiles weakly discriminated HS from IBS, although fibroblast growth factor 21 and IL6 serum levels were higher in IBS. Results were confirmed in a validation cohort (UCA, n = 15; UCR + IBS, n = 9; IBS, n = 14).

Conclusions

SIP profiles distinguish UC patients from IBS patients, irrespective of inflammation or IBS-like symptoms, suggesting that inflammatory mechanisms of the diseases are part of different spectrums.
Crushing method selection for non-centrifugal sugar production by FAHP–ELECTRE I
Authors: Srinivas M , Sravya B , Raj S Prudhvi , Reddy K S
Published: January 2020

The non-centrifugal sugar (NCS) industry is one of the oldest small-scale cottage industry in India, whose technological features are not changed for several decades due to which the production and consumption of NCS has reduced significantly. One way to attend this problem is to select the best and sustainable methods among the existing technologies at various stages in the production process. In the production of NCS, juice extraction is the primary and essential process. The present work gives an insight to a logical procedure for selecting a suitable and sustainable juice extraction method for improving the NCS production using multi-criteria evaluation (MCE) technique. The selection process is based on 11 evaluation criteria covering various sustainable factors viz. technological, economic and environmental factors. Fuzzy analytical hierarchical process (FAHP) integrated with elimination et choix traduisant la realité method is the MCE technique considered for selecting the most appropriate crushing method among five alternatives. The results indicated that the power-operated single horizontal crusher is the most suitable and sustainable crushing method for improving the production rate of NCS. The same technique can be used for the other process unit of the NCS production to improve the productivity and sustainability of NCS.
Effects of copper hydroxychloride on growth performance and abundance of genes involved in lipid metabolism of growing pigs
Authors: Espinosa Charmaine D , Fry R Scott , Kocher Matthew E , Stein Hans H
Published: January 2020

An experiment was conducted to test the hypothesis that copper (Cu) hydroxychloride improves growth performance by upregulating the mRNA transcription of genes involved in lipid metabolism of pigs fed a diet based on corn, soybean meal (SBM), and distillers dried grains with solubles (DDGS). Thirty-two pigs (15.05 ± 0.98 kg) were allotted to 2 dietary treatments with 2 pigs per pen for a total of 8 replicate pens per treatment. Pigs were fed a corn–SBM–DDGS control diet that included Cu to meet the requirement. A second diet was formulated by adding 150 mg Cu/kg from copper hydroxychloride to the control diet. On the last day of the experiment, one pig per pen was sacrificed, and samples from liver, skeletal muscle, and subcutaneous adipose tissue were collected to analyze relative mRNA abundance of genes involved in lipid metabolism. Results indicated that overall ADG and G:F were greater (P < 0.05) for pigs fed the diet containing copper hydroxychloride compared with pigs fed the control diet. Pigs fed the diet supplemented with copper hydroxychloride also had increased (P < 0.05) abundance of cluster of differentiation 36 in the liver and increased (P < 0.05) abundance of fatty acid-binding protein 4 and lipoprotein lipase in subcutaneous adipose tissue. Inclusion of copper hydroxychloride also tended to increase (P < 0.10) the abundance of fatty acid-binding protein 1, peroxisome proliferator-activated receptor α, and carnitine palmitoyltransferase 1B in the liver, skeletal muscle, and subcutaneous adipose tissue, respectively. This indicates that dietary Cu may affect signaling pathways associated with lipid metabolism by improving the uptake, transport, and utilization of fatty acids. In conclusion, supplementation of copper hydroxychloride to the control diet improved growth performance and upregulated the abundance of some genes involved in postabsorptive metabolism of lipids.
Product Lineups: The More You Search, The Less You Find
Authors: Park Sang Kyu , Sela Aner
Published: January 2020

Consumers often try to visually identify a previously encountered product among a sequence of similar items, guided only by their memory and a few general search terms. What determines their success at correctly identifying the target product in such “product lineups”? The current research finds that the longer consumers search sequentially, the more conservative and—ironically—inaccurate judges they become. Consequently, the more consumers search, the more likely they are to erroneously reject the correct target when it finally appears in the lineup. This happens because each time consumers evaluate a similar item in the lineup, and determine that it is not the option for which they have been looking, they draw an implicit inference that the correct target should feel more familiar than the similar items rejected up to that point. This causes the subjective feeling of familiarity consumers expect to experience with the true target to progressively escalate, making them more conservative but also less accurate judges. The findings have practical implications for consumers and marketers, and make theoretical contributions to research on inference-making, online search, and product recognition.
Population Genetic Diversity and Structure of Thrips tabaci (Thysanoptera: Thripidae) on Allium Hosts in China, Inferred From Mitochondrial COI Gene Sequences
Authors: Li Xiaowei , Zhang Zhijun , Zhang Jinming , Huang Jun , Wang Likun , Li Yehua , Hafeez Muhammad , Lu Yaobin
Published: January 2020

Thrips tabaci Lindeman is a widely distributed agricultural pest China, which causes damage to many vegetables and cash crops. However, the population genetic variation of this pest in China remains unknown. In this study, the genetic diversity and structure of T. tabaci on Allium hosts collected from 12 geographic locations were evaluated based on mitochondrial cytochrome oxidase subunit I (COI) sequences. Six haplotypes were identified in 247 T. tabaci individuals from 12 geographic locations. All the identified T. tabaci haplotypes were thelytokous populations. The strongest genetic differentiation and relatively low gene flow were found between QHXN and other locations, which might be due to geographic barriers, such as high altitude Qinghai-Tibet Plateau. The lowest genetic variation was found in eastern and southern regions, with only one haplotype identified. The Mantel test showed no correlation between genetic distance and geographical distances. High gene flow between locations with substantial geographical distances suggested that migration of T. tabaci across China might be facilitated through human activities. The results of demographic analysis suggested that T. tabaci in China have undergone a recent demographic expansion. The possible influences of T. tabaci invasion history and human activities on the current haplotype geographical distribution were interpreted and the implications of these findings for T. tabaci management were discussed.
Strange Cases: Jekyll & Hyde Narratives as Rhetorical Strategy in Sir Alexander Morison’s Physiognomy of Mental Diseases
Authors: Kearin Madeline Bourque
Published: January 2020

Sir Alexander Morison’s Physiognomy of Mental Diseases (1838) was created as a didactic tool for physicians, depicting lunatics in both the active and dormant states of disease. Through the act of juxtaposition, Morison constituted his subjects as their own Jekylls and Hydes, capable of radical transformation. In doing so, he marshaled artistic and clinical, visual and textual approaches in order to pose a particular argument about madness as a temporally manifested, visually distinguishable state defined by its contrast with reason. This argument served a crucial function in legitimizing the emergent discipline of psychiatry by applying biomedical methodologies to the observation and classification of distinctly physical symptoms. Robert Louis Stevenson’s “quintessentially Victorian parable” serves as a metaphor for the way 19th-century alienists conceptualized insanity, while the theme of duality at the core of Stevenson’s story serves as a framework for conceptualizing both psychiatry and the subjects it generates. It was (and is) a discipline formulated around narrative as the primary organizing structure for its particular set of paradoxes, and specifically, narratives of the self as a fluid, dynamic, and contradictory entity.
Effects of density dependence and climatic factors on population dynamics of Cricetulus barabensis: a 25-year field study
Authors: Shuai Ling-Ying , Wang Li-Qing , Yang Yu-Ping , Zhang Fu-Shun
Published: January 2020

Rodents often act as keystone species in communities and play important roles in shaping structures and functions of many ecosystems. Understanding the underlying mechanisms of population fluctuation in rodents is therefore of great interest. Using the data from a 25-year field survey carried out in Inner Mongolia, China, we explored the effects of density dependence, local climatic factors, and a large-scale climatic perturbation (El Niño–Southern Oscillation) on the population dynamics of the striped hamster (Cricetulus barabensis), a rodent widely distributed in northern China. We detected a strong negative density-dependent effect on the population dynamics of C. barabensis. Rainfall had a significant positive effect on population change with a 1-year lag. The pregnancy rate of C. barabensis was negatively affected by the annual mean temperature in the current year, but positively associated with the population density in the current year and the annual Southern Oscillation Index in the previous year. Moving-window analyses suggested that, with a window length of 12 years, there was a significant interaction between rainfall and density dependence, with increasing rainfall alleviating the negative effect of density dependence. As C. barabensis often causes agricultural damage and can transmit zoonotic diseases to human beings, our results also have implications for pest and disease control.
Insecticide Resistance Mechanisms in Triatoma infestans (Reduviidae: Triatominae): The Putative Role of Enhanced Detoxification and Knockdown Resistance (kdr) Allele in a Resistant Hotspot From the Argentine Chaco
Authors: Fronza Georgina , Roca-Acevedo Gonzalo , Mougabure-Cueto Gaston A , Sierra Ivana , Capriotti Natalia , Toloza Ariel C
Published: January 2020

Chagas disease affects around 6 million people in the world, and in Latin America, it is mainly transmitted by the kissing bug. Chemical control of the vector with pyrethroid insecticides has been the most frequently used tool to reduce the disease incidence. Failures of field control have been detected in areas of the Argentinian Gran Chaco that correlate with high levels of insecticide resistance. Here, we provide evidence of the mechanisms involved in the resistance to insecticides of field populations of T. infestans from General Güemes Department (Chaco Province, Argentina). The biochemical analysis suggests the increase in the activity of the degradative enzymes P450 oxidases and esterases as a minor contributive mechanism in low-resistance populations. The molecular study revealed high frequencies of the kdr L925I mutation at the voltage-gated sodium channel as responsible for the high resistance ratios detected. This knowledge contributes to the generation of comprehensive vector control strategies that reduce the incidence of the disease.
Biting Rates and Onchocerca Infectivity Status of Black Flies from the Simulium damnosum Complex (Diptera: Simuliidae) in Osun State, Nigeria
Authors: Oforka Linda C , Adeleke Monsuru A , Anikwe Joseph C , Hardy Nate B , Mathias Derrick K , Makanjuola Winifred A , Fadamiro Henry Y
Published: January 2020

The Simulium damnosum Theobald complex transmits Onchocerca volvulus Leuckart (Spirurida: Onchocercidae), the causative agent of onchocerciasis. Recent evidence suggests that control efforts have strongly suppressed parasite populations, but vector surveillance is needed in parts of Africa where the disease remains endemic. Here, studies on biting rates and infectivity status of suspected vector species were conducted in three onchocerciasis-endemic areas, namely Iwo, Ede, and Obokun, in Osun State, Nigeria. A total of 3,035 black flies were collected between October 2014 and September 2016, and examined for parity and parasites using standard methods. A separate collection of 2,000 black flies was pool-screened for infectivity using polymerase chain reaction (PCR) amplification of the O-150 marker. Results showed that parous flies were significantly less common than nulliparous flies with overall parous rates of 8.02% in Iwo and 35.38% in Ede at the end of the study period. Obokun had a parous rate of 22.22% obtained in the first year only. None of the dissected parous flies were infected with O. volvulus and PCR assays showed no amplification of O-150 O. volvulus-specific repeats in head and body pools. However, annual biting rates exceeded the World Health Organization threshold of 1,000 bites/person/yr. Thus it appears that, with such high rates of biting, even low levels of vector infection can sustain onchocerciasis in African communities.
A Survey of Music Therapists Working in Pediatric Medical Settings in the United States
Authors: Knott David , Biard Marial , Nelson Kirsten E , Epstein Stephanie , Robb Sheri L , Ghetti Claire M
Published: January 2020

Music therapy is becoming a standard supportive care service in many pediatric hospitals across the United States. However, more detailed information is needed to advance our understanding about current clinical practice and increase availability of pediatric music therapy services. The purpose of this cross-sectional survey study was to collect and summarize data about music therapists working in pediatric medical settings. Specifically, we collected information about (1) therapist demographics, (2) organizational structure, (3) service delivery and clinical practice, and (4) administrative/supervisory responsibilities. Board-certified music therapists working in pediatric medical settings (n = 118) completed a 37-item online questionnaire. We analyzed survey data using descriptive statistics and content analysis. Findings indicated that there is a ratio of approximately one music therapist for every 100 patient beds, that one-third of respondents are the only music therapist in their setting, and that half of the surveyed positions are philanthropically funded. Prioritizing patient referrals based on acuity was common (95.7%, n = 110), with palliative care and pain as the most highly prioritized needs. More than half of respondents reported serving in high acuity areas such as the pediatric intensive care, hematology/oncology, or neonatal intensive care units. We recommend replication of this survey in five years to examine growth and change in service delivery among pediatric music therapists over time, with additional studies to (a) explore how therapist-to-patient ratios influence quality of care, (b) identify factors that contribute to sustainability of programs, and (c) determine how expansion of services support a broader population of patients and families.
Abuse of Process: An Impossible Dialogue Between ICJ and ICSID Tribunals?
Authors: Ceretelli Carlotta
Published: January 2020

In the backdrop of the proliferation of international courts, the abuse of process revealed its protean nature. Still a foreigner in the International Court of Justice’s (ICJ or the Court) jurisprudence, in investment treaty arbitration it has been shaped in different ways to face multiple forms of the improper use of judicial system. Recently, the cases Immunities and Criminal Proceedings and Application of the International Convention on the Elimination of All Forms of Racial Discrimination have offered two precious occasions of dialogue between ICJ and the tribunals established under the auspices of the International Centre for the Settlement of Investments Disputes (ICSID). Once compared the arguments made on the matter of abuse of procedure in the cases at hand with ICSID case law on treaty shopping and parallel proceedings, the scope of the present contribution will be to understand whether the abuse of process can really become the protagonist of a fruitful interaction between judicial organs.
Reorganizing the Neighborhood? Power Shifts and Regional Security Organizations in the Post-Soviet Space and Latin America
Authors: Weiffen Brigitte , Gawrich Andrea , Axyonova Vera
Published: January 2020

The article explores how power shifts in world politics and the emergence of regional powers affect regional security governance. We identify the post-Soviet space and Latin America as two regions where a traditional hegemon and Cold War superpower (the United States and Russia, respectively) has recently been challenged by a rising power (Brazil and China). In both regions, an older regional organization shaped by Cold War dynamics exists alongside a newer organization shaped by the rising power. But do similar patterns of power shifts lead to analogous types and trajectories of security governance? We analyze four security organizations from the two regions: the Organization for Security and Co-operation in Europe (OSCE) and the Shanghai Cooperation Organization (SCO) from the post-Soviet space, and the Organization of American States (OAS) and the Union of South American Nations (UNASUR) from Latin America. We show how power shifts are reflected in (1) the factors driving organizational foundation and transformation, (2) the organizations’ security conceptions and practices, and (3) organizational overlap. Responding to the call for more studies in comparative regionalism, this article contributes to the debate on how powers of various kinds shape regions, regional organizations, and their security priorities, and adds new insights to research on overlapping regionalism.
Les Combattants—Ideologies of Exile, Return and Nationalism in the DRC
Authors: Mbu-Mputu Norbert , Trapido Joe
Published: January 2020

Focused on London, this article looks at the ideology and practice of Congolese nationalism in exile, and at the ideas of home, belonging and return connected with this. Democratic Republic of Congo (DRC) migrants came to Western Europe escaping violence and economic and political collapse but, for a long time, the imaginative concentration of the diaspora was not on politics, but on a consumer-based version of the good life. This article traces how this changed in the 2000s with the diaspora becoming a focus for violent and racialized forms of nationalism. Tracing this evolution historically, we look at how the practices and ideologies of ‘return’ and ‘home’ have come to express this transformation of exile nationalism.
Dependence of gravitational wave transient rates on cosmic star formation and metallicity evolution history
Authors: Tang Petra N , Eldridge J J , Stanway Elizabeth R , Bray J C
Published: January 2020

We compare the impacts of uncertainties in both binary population synthesis models and the cosmic star formation history on the predicted rates of gravitational wave (GW) compact binary merger events. These uncertainties cause the predicted rates of GW events to vary by up to an order of magnitude. Varying the volume-averaged star formation rate density history of the Universe causes the weakest change to our predictions, while varying the metallicity evolution has the strongest effect. Double neutron star merger rates are more sensitive to assumed neutron star kick velocity than the cosmic star formation history. Varying certain parameters affects merger rates in different ways depending on the mass of the merging compact objects; thus some of the degeneracy may be broken by looking at all the event rates rather than restricting ourselves to one class of mergers.
Lysine acetylation of the housekeeping sigma factor enhances the activity of the RNA polymerase holoenzyme
Authors: Kim Ji-Eun , Choi Joon-Sun , Kim Jong-Seo , Cho You-Hee , Roe Jung-Hye
Published: January 2020

Protein lysine acetylation, one of the most abundant post-translational modifications in eukaryotes, occurs in prokaryotes as well. Despite the evidence of lysine acetylation in bacterial RNA polymerases (RNAPs), its function remains unknown. We found that the housekeeping sigma factor (HrdB) was acetylated throughout the growth of an actinobacterium, Streptomyces venezuelae, and the acetylated HrdB was enriched in the RNAP holoenzyme complex. The lysine (K259) located between 1.2 and 2 regions of the sigma factor, was determined to be the acetylated residue of HrdB in vivo by LC–MS/MS analyses. Specifically, the label-free quantitative analysis revealed that the K259 residues of all the HrdB subunits were acetylated in the RNAP holoenzyme. Using mutations that mimic or block acetylation (K259Q and K259R), we found that K259 acetylation enhances the interaction of HrdB with the RNAP core enzyme as well as the binding activity of the RNAP holoenzyme to target promoters in vivo. Taken together, these findings provide a novel insight into an additional layer of modulation of bacterial RNAP activity.
A multi-modal coarse grained model of DNA flexibility mappable to the atomistic level
Authors: Walther Jürgen , Dans Pablo D , Balaceanu Alexandra , Hospital Adam , Bayarri Genís , Orozco Modesto
Published: January 2020

We present a new coarse grained method for the simulation of duplex DNA. The algorithm uses a generalized multi-harmonic model that can represent any multi-normal distribution of helical parameters, thus avoiding caveats of current mesoscopic models for DNA simulation and representing a breakthrough in the field. The method has been parameterized from accurate parmbsc1 atomistic molecular dynamics simulations of all unique tetranucleotide sequences of DNA embedded in long duplexes and takes advantage of the correlation between helical states and backbone configurations to derive atomistic representations of DNA. The algorithm, which is implemented in a simple web interface and in a standalone package reproduces with high computational efficiency the structural landscape of long segments of DNA untreatable by atomistic molecular dynamics simulations.
CRISPR-Cas12a based internal negative control for nonspecific products of exponential rolling circle amplification
Authors: Tian Bo , Minero Gabriel Antonio S , Fock Jeppe , Dufva Martin , Hansen Mikkel Fougt
Published: January 2020

False-positive results cause a major problem in nucleic acid amplification, and require external blank/negative controls for every test. However, external controls usually have a simpler and lower background compared to the test sample, resulting in underestimation of false-positive risks. Internal negative controls, performed simultaneously with amplification to monitor the background level in real-time, are therefore appealing in both research and clinic. Herein, we describe a nonspecific product-activated single-stranded DNA-cutting approach based on CRISPR (clustered regularly interspaced short palindromic repeats) Cas12a (Cpf1) nuclease. The proposed approach, termed Cas12a-based internal referential indicator (CIRI), can indicate the onset of nonspecific amplification in an exponential rolling circle amplification strategy here combined with an optomagnetic readout. The capability of CIRI as an internal negative control can potentially be extended to other amplification strategies and sensors, improving the performance of nucleic acid amplification-based methodologies.
Prediction of all-cause mortality in haemodialysis patients using a Bayesian network
Authors: Siga Marleine Mefeugue , Ducher Michel , Florens Nans , Roth Hubert , Mahloul Nadir , Fouque Denis , Fauvel Jean-Pierre
Published: January 2020

Background

All-cause mortality in haemodialysis (HD) is high, reaching 15.6% in the first year according to the European Renal Association.

Methods

A new clinical tool to predict all-cause mortality in HD patients is proposed. It uses a post hoc analysis of data from the prospective cohort study Photo-Graph V3. A total of 35 variables related to patient characteristics, laboratory values and treatments were used as predictors of all-cause mortality. The first step was to compare the results obtained using a logistic regression to those obtained by a Bayesian network. The second step aimed to increase the performance of the best prediction model using synthetic data. Finally, a compromise between performance and ergonomics was proposed by reducing the number of variables to be entered in the prediction tool.

Results

Among the 9010 HD patients included in the Photo-Graph V3 study, 4915 incident patients with known medical status at 2 years were analysed. All-cause mortality at 2 years was 34.1%. The Bayesian network provided the most reliable prediction. The final optimized models that used 14 variables had areas under the receiver operating characteristic curves of 0.78 ± 0.01, sensitivity of 72 ± 2%, specificity of 69 ± 2%, predictive positive value of 70 ± 1% and negative predictive value of 71 ± 2% for the prediction of all-cause mortality.

Conclusions

Using artificial intelligence methods, a new clinical tool to predict all-cause mortality in incident HD patients is proposed. The latter can be used for research purposes before its external validation at: https://www.hed.cc/? a=twoyearsallcausemortalityhemod&n=2-years%20All-cause%20Mortality%20Hemodialysis.neta.
KIF11 and KIF15 mitotic kinesins are potential therapeutic vulnerabilities for malignant peripheral nerve sheath tumors
Authors: Terribas Ernest , Fernández Marco , Mazuelas Helena , Fernández-Rodríguez Juana , Biayna Josep , Blanco Ignacio , Bernal Gabriela , Ramos-Oliver Irma , Thomas Craig , Guha Rajiv , Zhang Xiaohu , Gel Bernat , Romagosa Cleofé , Ferrer Marc , Lázaro Conxi , Serra Eduard
Published: January 2020

Background

Malignant peripheral nerve sheath tumor (MPNST) constitutes the leading cause of neurofibromatosis type 1–related mortality. MPNSTs contain highly rearranged hyperploid genomes and exhibit a high division rate and aggressiveness. We have studied in vitro whether the mitotic kinesins KIF11, KIF15, and KIF23 have a functional role in maintaining MPNST cell survival and can represent potential therapeutic vulnerabilities.

Methods

We studied the expression of kinesin mRNAs and proteins in tumors and cell lines and used several in vitro functional assays to analyze the impact of kinesin genetic suppression (KIF15, KIF23) and drug inhibition (KIF11) in MPNST cells. We also performed in vitro combined treatments targeting KIF11 together with other described MPNST targets.

Results

The studied kinesins were overexpressed in MPNST samples. KIF15 and KIF23 were required for the survival of MPNST cell lines, which were also more sensitive than benign control fibroblasts to the KIF11 inhibitors ispinesib and ARRY-520. Co-targeting KIF11 and BRD4 with ARRY-520 and JQ1 reduced MPNST cell viability, synergistically killing a much higher proportion of MPNST cells than control fibroblasts. In addition, genetic suppression of KIF15 conferred an increased sensitivity to KIF11 inhibitors alone or in combination with JQ1.

Conclusions

The mitotic spindle kinesins KIF11 and KIF15 and the cytokinetic kinesin KIF23 play a clear role in maintaining MPNST cell survival and may represent potential therapeutic vulnerabilities. Although further in vivo evidences are still mandatory, we propose a simultaneous suppression of KIF11, KIF15, and BRD4 as a potential therapy for MPNSTs.
MCT4 regulates de novo pyrimidine biosynthesis in GBM in a lactate-independent manner
Authors: Spina Raffaella , Voss Dillon M , Yang Xiaohua , Sohn Jason W , Vinkler Robert , Schraner Julianna , Sloan Anthony , Welford Scott M , Avril Norbert , Ames Heather M , Woodworth Graeme F , Bar Eli E
Published: January 2020

Background

Necrotic foci with surrounding hypoxic cellular pseudopalisades and microvascular hyperplasia are histological features found in glioblastoma (GBM). We have previously shown that monocarboxylate transporter 4 (MCT4) is highly expressed in necrotic/hypoxic regions in GBM and that increased levels of MCT4 are associated with worse clinical outcomes.

Methods

A combined transcriptomics and metabolomics analysis was performed to study the effects of MCT4 depletion in hypoxic GBM neurospheres. Stable and inducible MCT4-depletion systems were used to evaluate the effects of and underlining mechanisms associated with MCT4 depletion in vitro and in vivo, alone and in combination with radiation.

Results

This study establishes that conditional depletion of MCT4 profoundly impairs self-renewal and reduces the frequency and tumorigenicity of aggressive, therapy-resistant, glioblastoma stem cells. Mechanistically, we observed that MCT4 depletion induces anaplerotic glutaminolysis and abrogates de novo pyrimidine biosynthesis. The latter results in a dramatic increase in DNA damage and apoptotic cell death, phenotypes that were readily rescued by pyrimidine nucleosides supplementation. Consequently, we found that MCT4 depletion promoted a significant prolongation of survival of animals bearing established orthotopic xenografts, an effect that was extended by adjuvant treatment with focused radiation.

Conclusions

Our findings establish a novel role for MCT4 as a critical regulator of cellular deoxyribonucleotide levels and provide a new therapeutic direction related to MCT4 depletion in GBM.
Ultrafast growth of large single crystals of monolayer WS2 and WSe2
Authors: Zhang Zhengwei , Chen Peng , Yang Xiangdong , Liu Yuan , Ma Huifang , Li Jia , Zhao Bei , Luo Jun , Duan Xidong , Duan Xiangfeng
Published: January 2020

Monolayer transition metal dichalcogenides (TMDs) have attracted considerable attention as atomically thin semiconductors for the ultimate transistor scaling. For practical applications in integrated electronics, large monolayer single crystals are essential for ensuring consistent electronic properties and high device yield. The TMDs available today are generally obtained by mechanical exfoliation or chemical vapor deposition (CVD) growth, but are often of mixed layer thickness, limited single crystal domain size or have very slow growth rate. Scalable and rapid growth of large single crystals of monolayer TMDs requires maximization of lateral growth rate while completely suppressing the vertical growth, which represents a fundamental synthetic challenge and has motivated considerable efforts. Herein we report a modified CVD approach with controllable reverse flow for rapid growth of large domain single crystals of monolayer TMDs. With the use of reverse flow to precisely control the chemical vapor supply in the thermal CVD process, we can effectively prevent undesired nucleation before reaching optimum growth temperature and enable rapid nucleation and growth of monolayer TMD single crystals at a high temperature that is difficult to attain with use of a typical thermal CVD process. We show that monolayer single crystals of 450 μm lateral size can be prepared in 10 s, with the highest lateral growth rate up to 45 μm/s. Electronic characterization shows that the resulting monolayer WSe2 material exhibits excellent electronic properties with carrier mobility up to 90 cm2 V−1 s−1, comparable to that of the best exfoliated monolayers. Our study provides a robust pathway for rapid growth of high-quality TMD single crystals.
Antibiotic Prescribing in New York State Medicare Part B Beneficiaries Diagnosed With Cystitis Between 2016 and 2017
Authors: Yu Joyce Y , McKenna Valerie A , Dumyati Ghinwa K , Lubowski Teresa J , Carreno Joseph J
Published: January 2020

Background

Statewide tracking and reporting is an outpatient antimicrobial stewardship tool that may be useful for many stakeholders. However, to date, these evaluations have been limited. This study aimed to track and report outpatient antibiotic prescribing in Medicare Part B enrollees diagnosed with cystitis in the outpatient setting.

Methods

This was a retrospective, cohort study of Medicare Part B enrollees in New York State. Inclusion criteria include outpatient visit in 2016 or 2017, cystitis diagnosis code, and oral antibiotic prescription ≤3 days after diagnosis of cystitis. Antibiotics were categorized as first-line, oral β-lactams, fluoroquinolones, or other per Infectious Diseases Society of America acute uncomplicated cystitis guidelines. Data were stratified by sex. Annual prescriptions proportions were compared using χ 2 test or Fisher’s exact test as appropriate.

Results

A total of 50 658 prescriptions were included. For females’ prescriptions, first line increased (41.5% vs 43.8%, P < .0001), oral β-lactams increased (17.8% vs 20.5%, P < .0001), fluoroquinolones decreased (34.1% vs 29.1%, P < .0001), and other increased (6.5% vs 6.6%, P = .76) in 2017. For males’ prescriptions, first line increased (25.2% vs 26.7%, P = .11), oral β-lactams increased (23.1% vs 26.2%, P = .0003), fluoroquinolones decreased (44.0% vs 39.3%, P < .0001), and other remained unchanged (7.8% vs 7.8%, P = .92) in 2017.

Conclusions

Guideline concordant therapy prescribing for cystitis increased among Medicare Part B beneficiaries in New York State between 2016 and 2017. However, there was still a high prevalence of fluoroquinolone prescribing. These data highlight the need for additional outpatient antimicrobial stewardship efforts in New York State.
In Vitro Pharmacodynamic Analyses Help Guide the Treatment of Multidrug-Resistant Enterococcus faecium and Carbapenem-Resistant Enterobacter cloacae Bacteremia in a Liver Transplant Patient
Authors: Wenzler Eric , Santarossa Maressa , Meyer Kevin A , Harrington Amanda T , Reid Gail E , Clark Nina M , Albarillo Fritzie S , Bulman Zackery P
Published: January 2020

Background

Infections due to multidrug-resistant pathogens are particularly deadly and difficult to treat in immunocompromised patients, where few data exist to guide optimal antimicrobial therapy. In the absence of adequate clinical data, in vitro pharmacokinetic (PK)/pharmacodynamic (PD) analyses can help to design treatment regimens that are bactericidal and may be clinically effective.

Methods

We report a case in which in vitro pharmacodynamic analyses were utilized to guide the treatment of complex, recurrent bacteremias due to vancomycin-, daptomycin-, and linezolid-resistant Enterococcus faecium and carbapenem-resistant Enterobacter cloacae complex in a liver transplant patient.

Results

Whole-genome sequencing revealed unique underlying resistance mechanisms and explained the rapid evolution of phenotypic resistance and complicated intrahost genomic dynamics observed in vivo. Performing this comprehensive genotypic and phenotypic testing and time-kill analyses, along with knowledge of institution and patient-specific factors, allowed us to use precision medicine to design a treatment regimen that maximized PK/PD.

Conclusions

This work provides a motivating example of clinicians and scientists uniting to optimize care in the era of escalating antimicrobial resistance.
Genetic Determinants of Trehalose Utilization Are Not Associated With Severe Clostridium difficile Infection Outcome
Authors: Saund Katie , Rao Krishna , Young Vincent B , Snitkin Evan S
Published: January 2020

In a case–control study of patients with Clostridium difficile infection, we found no statistically significant association between the presence of trehalose utilization variants in infecting C. difficile strains and development of severe infection outcome. These results do not support trehalose utilization conferring enhanced virulence in the context of human C. difficile infections.
Fishing for a Diagnosis, the Impact of Delayed Diagnosis on the Course of Mycobacterium marinum Infection: 21 Years of Experience at a Tertiary Care Hospital
Authors: Castillo Natalia E , Gurram Pooja , Sohail M Rizwan , Fida Madiha , Abu Saleh Omar
Published: January 2020

Background

Mycobacterium marinum is a common but underreported mycobacterial infection. We conducted a large retrospective study to determine risk factors and describe the therapeutic interventions and outcomes in patients with uncomplicated and complicated M. marinum infection.

Methods

Culture-confirmed M. marinum infection cases were identified from the Mayo Clinic Clinical Mycology Laboratory from January 1998 to December 2018. Complicated M. marinum infection was defined as the presence of tenosynovitis, septic arthritis, or osteomyelitis. Differences in complicated vs uncomplicated M. marinum infections were analyzed using statistical comparisons.

Results

Twelve cases had a complicated M. marinum infection. Patients with a complicated infection were older (64.3 ± 11.1 vs 55.8 ± 14.5; P = .03), had longer duration of symptoms (5 vs 3 months; P = .011), and had more surgical debridements (1 vs 0; P < .001). Length of treatment and number of drugs used were not statistically significant. Complicated M. marinum cases received more medications (2 vs 1; P = .263) and were treated longer (5.7 vs 3.5 months; P = .067). Antibiotic susceptibilities were performed in 59% of the patients. All isolates were susceptible to clarithromycin. From the tetracyclines, doxycycline had a better susceptibility pattern.

Conclusions

M. marinum infection is an important cause of skin and soft tissue infection. Poor water exposure documentation, unusual clinical presentation, and empiric antibiotic treatment before definitive M. marinum diagnosis often contribute to a delayed diagnosis. Complicated M. marinum cases had longer duration of symptoms and more surgical debridements. No difference in the number of drugs used or clinical outcome was observed.
Eosinopenia and Binary Toxin Increase Mortality in Hospitalized Patients With Clostridioides difficile Infection
Authors: Carlson Travis J , Endres Bradley T , Le Pham Julie , Gonzales-Luna Anne J , Alnezary Faris S , Nebo Kimberly , Miranda Julie , Lancaster Chris , Bassères Eugénie , Begum Khurshida , Alam M Jahangir , Reveles Kelly R , Garey Kevin W
Published: January 2020

Background

Patients with Clostridioides difficile infection (CDI) with either eosinopenia or infected with a binary toxin strain have increased likelihood of mortality. However, the relationship between binary toxin and eosinopenia to synergistically increase mortality has not been studied in humans. We hypothesized that patients with CDI due to binary toxin strains and concomitant peripheral eosinopenia would have a higher likelihood of inpatient mortality.

Methods

This multicenter, retrospective cohort study included adult patients with CDI of known ribotypes stratified by eosinopenia, defined as an absence of eosinophils in the peripheral blood (Houston cohort). The primary outcome was inpatient mortality. Results were supported by a separate national cohort of veterans with CDI (Veterans’ cohort).

Results

In the Houston cohort, a total of 688 patients from 13 institutions in 6 cities were included. Of these, 132 (19%) had an eosinophil count of 0.0 cells/µL (0.0 cells*109/L) and 109 (16%) were infected with a binary toxin strain. After adjusting for covariates, the combination of eosinopenia and infection with a binary toxin strain was an independent predictor of inpatient mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 1.9–33.2; P = .005). In the separate Veterans’ cohort (n = 790), this combination was also a significant predictor of inpatient mortality (OR, 6.1; 95% CI, 1.5–23.9; P = .009).

Conclusions

In conclusion, the combination of eosinopenia and CDI due to a binary toxin strain was correlated with increased mortality in hospitalized patients from 2 independent cohorts. Prospective studies should further study this important subset of patients at the time of CDI diagnosis.
A Randomized Controlled Trial Assessing the Evolution of the Weight-Bearing Ankle Dorsiflexion Range of Motion Over 6 Sessions of Talus Mobilizations in Older Adults
Authors: Hernández-Guillén David , Blasco José-María
Published: January 2020

Background

Ankle range of motion declines with age, affecting mobility and postural control.

Objective

The objective of this study was to investigate the effects of a talus mobilization-based intervention among healthy community-dwelling older adults presenting with limited weight-bearing ankle dorsiflexion range of motion and determine how ankle mobility evolved over the treatment.

Design

This was a randomized clinical trial.

Setting

This study was conducted in an outpatient clinic.

Participants

Community-dwelling, older adults over 60 years of age who had limited ankle mobility participated in this study.

Interventions

The experimental intervention consisted of 6 sessions of manual therapy applied in the ankle joint. The control group received the same volume of sham treatment.

Measurements

The primary outcome was the weight-bearing ankle dorsiflexion range of motion as measured using the lunge test. Data were collected at 9 time points: baseline, after each session, and follow-up.

Results

A total of 36 participants were analyzed. A single session of mobilization increased ankle range of motion by 8 degrees (95% confidence interval = 6 to 11). At the end of the sixth session, this effect had increased slightly to 11 degrees (95% confidence interval = 9 to 13). Significant between-group differences were found throughout the intervention.

Limitations

Optimal dose and effects from follow-up evaluations for treatment volumes of fewer than 6 sessions remain unknown.

Conclusions

Six sessions of a talus mobilization-based intervention in healthy community-dwelling older adults found that the greatest mobility gain in terms of the weight-bearing ankle dorsiflexion range of motion is produced after the first session. Additional sessions produce smaller improvements with a slight upward trend. Importantly, the restoration of joint mobility is enhanced over time after the end of the intervention.
What Really Works in Intervention? Using Fidelity Measures to Support Optimal Outcomes
Authors: An Mihee , Dusing Stacey C , Harbourne Regina T , Sheridan Susan M ,   START-Play Consortium
Published: January 2020

A critical factor to move the field of physical therapy forward is the measurement of fidelity during comparisons of interventions. Fidelity translates as “faithfulness”; thus, fidelity of intervention means faithful and correct implementation of the key components of a defined intervention. Fidelity measurement guards against deviations from, or drift in, the delivery of a targeted intervention, a process necessary for evaluating the efficacy of rehabilitation approaches. Importantly, attention to fidelity measurement differentiates rehabilitation approaches from each other. However, earlier research comparing physical therapist interventions often reported findings without careful attention to fidelity measurement. The purpose of this paper is 2-fold: (1) to support the development of intervention-specific fidelity measures in physical therapy research as the gold standard for translating research findings to clinical practice, and (2) to describe the process of creating a multi-dimensional fidelity measurement instrument in rehabilitation intervention. Improved attention to fidelity measurement will allow the rehabilitation field to communicate interventions clearly with a direct link to outcomes and target the implementation of our improved intervention for the right patient problem with the right dose and the right ingredients at the right time.
A gift for gratitude and cooperative behavior: brain and cognitive effects
Authors: Balconi Michela , Fronda Giulia , Vanutelli Maria Elide
Published: January 2020

Recently, different psychological studies have been interested in identifying the factors that regulate the development and maintenance of long-lasting interpersonal and social relationships. Specifically, the present research explored the link between gift exchange, gratitude and cognitive effects. The behavioral performance and neural activity of 32 participants were recorded during a cooperative game to be played before and after gift exchange. Specifically, participants had to perform the task coupled with a dear friend. Half of the couples were asked to exchange a gift before the task performance; the other half was asked to exchange a gift halfway through the task performance. For hemodynamic brain responses, functional near-infrared spectroscopy was used. Results showed that an increase in cognitive performance occurred after the exchange of gifts, with improved accuracy and lower response times in task performance. Regarding hemodynamic responses, an increase in oxygenated hemoglobin was detected, especially in the dorsolateral prefrontal cortex following the gift exchange. Furthermore, it was observed that gift exchange before the beginning of the task increased the performance level. The present study provides a significant contribution to the identification of those factors that enable the increased cognitive performance based on cooperative relationships.