bluuebunny/crossref_metadata_2025_split huggingface dataset:
The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis
Authors: Rosenthal Alex , Gabrielian Andrei , Engle Eric , Hurt Darrell E. , Alexandru Sofia , Crudu Valeriu , Sergueev Eugene , Kirichenko Valery , Lapitskii Vladzimir , Snezhko Eduard , Kovalev Vassili , Astrovko Andrei , Skrahina Alena , Taaffe Jessica , Harris Michael , Long Alyssa , Wollenberg Kurt , Akhundova Irada , Ismayilova Sharafat , Skrahin Aliaksandr , Mammadbayov Elcan , Gadirova Hagigat , Abuzarov Rafik , Seyfaddinova Mehriban , Avaliani Zaza , Strambu Irina , Zaharia Dragos , Muntean Alexandru , Ghita Eugenia , Bogdan Miron , Mindru Roxana , Spinu Victor , Sora Alexandra , Ene Catalina , Vashakidze Sergo , Shubladze Natalia , Nanava Ucha , Tuzikov Alexander , Tartakovsky Michael 
Published: September 2017

ABSTRACT

The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top
Mycobacterium tuberculosis
lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at
https://tbportals.niaid.nih.gov/
.
Genomic Characterization of Urethritis-Associated Neisseria meningitidis Shows that a Wide Range of N. meningitidis Strains Can Cause Urethritis
Authors: Ma Kevin C. , Unemo Magnus , Jeverica Samo , Kirkcaldy Robert D. , Takahashi Hideyuki , Ohnishi Makoto , Grad Yonatan H. 
Published: September 2017

ABSTRACT

Neisseria meningitidis
, typically a resident of the oro- or nasopharynx and the causative agent of meningococcal meningitis and meningococcemia, is capable of invading and colonizing the urogenital tract. This can result in urethritis, akin to the syndrome caused by its sister species,
N. gonorrhoeae
, the etiologic agent of gonorrhea. Recently, meningococcal strains associated with outbreaks of urethritis were reported to share genetic characteristics with the gonococcus, raising the question of the extent to which these strains contain features that promote adaptation to the genitourinary niche, making them gonococcus-like and distinguishing them from other
N. meningitidis
strains. Here, we analyzed the genomes of 39 diverse
N. meningitidis
isolates associated with urethritis, collected independently over a decade and across three continents. In particular, we characterized the diversity of the nitrite reductase gene (
aniA
), the factor H-binding protein gene (
fHbp
), and the capsule biosynthetic locus, all of which are loci previously suggested to be associated with urogenital colonization. We observed notable diversity, including frameshift variants, in
aniA
and
fHbp
and the presence of intact, disrupted, and absent capsule biosynthetic genes, indicating that urogenital colonization and urethritis caused by
N. meningitidis
are possible across a range of meningococcal genotypes. Previously identified allelic patterns in urethritis-associated
N. meningitidis
strains may reflect genetic diversity in the underlying meningococcal population rather than novel adaptation to the urogenital tract.
Three Conserved Regions in Baculovirus Sulfhydryl Oxidase P33 Are Critical for Enzymatic Activity and Function
Authors: Kuang Wenhua , Zhang Huanyu , Wang Manli , Zhou Ning-Yi , Deng Fei , Wang Hualin , Gong Peng , Hu Zhihong 
Published: September 2017

ABSTRACT

Baculoviruses encode a conserved sulfhydryl oxidase, P33, which is necessary for budded virus (BV) production and multinucleocapsid occlusion-derived virus (ODV) formation. Here, the structural and functional relationship of P33 was revealed by X-ray crystallography, site-directed mutagenesis, and functional analysis. Based on crystallographic characterization and structural analysis, a series of P33 mutants within three conserved regions, i.e., the active site, the dimer interface, and the R127-E183 salt bridge, were constructed.
In vitro
experiments showed that mutations within the active site and dimer interface severely impaired the sulfhydryl oxidase activity of P33, while the mutations in the salt bridge had a relatively minor influence. Recombinant viruses containing mutated P33 were constructed and assayed
in vivo
. Except for the active-site mutant AXXA, all other mutants produced infectious BVs, although certain mutants had a decreased BV production. The active-site mutant H114A, the dimer interface mutant H227D, and the salt bridge mutant R127A-E183A were further analyzed by electron microscopy and bioassays. The occlusion bodies (OBs) of mutants H114A and R127A-E183A had a ragged surface and contained mostly ODVs with a single nucleocapsid. The OBs of all three mutants contained lower numbers of ODVs and had a significantly reduced oral infectivity in comparison to control virus. Crystallographic analyses further revealed that all three regions may coordinate with one another to achieve optimal function of P33. Taken together, our data revealed that all the three conserved regions are involved in P33 activity and are crucial for virus morphogenesis and peroral infectivity.

IMPORTANCE
Sulfhydryl oxidase catalyzes disulfide bond formation of substrate proteins. P33, a baculovirus-encoded sulfhydryl oxidase, is different from other cellular and viral sulfhydryl oxidases, bearing unique features in tertiary and quaternary structure organizations. In this study, we found that three conserved regions, i.e., the active site, dimer interface, and the R127-E183 salt bridge, play important roles in the enzymatic activity and function of P33. Previous observations showed that deletion of
p33
results in a total loss of budded virus (BV) production and in morphological changes in occlusion-derived virus (ODV). Our study revealed that certain P33 mutants lead to occlusion bodies (OBs) with a ragged surface, decreased embedded ODVs, and reduced oral infectivity. Interestingly, some P33 mutants with impaired ODV/OB still retained BV productivity, indicating that the impacts on BV and on ODV/OB are two distinctly different functions of P33, which are likely to be performed via different substrate proteins.
Hearing the voices of children and young people to develop and test a patient-reported experience measure in a specialist paediatric setting
Authors: Wray Jo , Hobden Sylvie , Knibbs Sarah , Oldham Geralyn 
Published: September 2017

ObjectiveTo develop and test patient-reported experience measures (PREMs) for children and young people in a specialist paediatric hospital setting.DesignSix PREMs were developed and tested by children and young people for children and young people aged 8–11, 12–13 and 14–16 years in inpatient and outpatient settings. A week-long pilot was implemented across inpatient wards and outpatient clinics to identify facilitators and barriers to the routine use of PREMs in a real-time setting across our organisation.SettingTertiary paediatric hospital.Main outcome measuresFinal PREMs; identified facilitators and barriers to implementation.Participants543 children and young people aged 8–16 years attending outpatient clinics or inpatient wards across a range of specialties.ResultsThree key themes about hospital experience were identified during focus groups: facilities, treatment and tests and people working at the hospital, and these provided the structure for the questionnaires. During cognitive testing the questionnaires were generally understood but some revisions to language and length of the questionnaires were required. Two designs were selected for the final PREMs. During acceptability and feasibility testing it was evident that children and young people liked the PREMs and wanted to give feedback on their hospital experience. Particular challenges for routine use of the PREMs focused on sustainability and resources.ConclusionsThe new PREMs will provide children and young people receiving care in specialist paediatric hospitals with the opportunity to provide feedback on their experience. Sustainability and ensuring that feedback results in improvements need to be addressed in future work.
Health system effects of implementing integrated community case management (iCCM) intervention in private retail drug shops in South Western Uganda: a qualitative study
Authors: Kitutu Freddy Eric , Mayora Chrispus , Johansson Emily White , Peterson Stefan , Wamani Henry , Bigdeli Maryam , Shroff Zubin Cyrus 
Published: September 2017

BackgroundIntervening in private drug shops to improve quality of care and enhance regulatory oversight may have health system effects that need to be understood before scaling up any such interventions. We examine the processes through which a drug shop intervention culminated in positive unintended effects and other dynamic interactions within the underlying health system.MethodsA multifaceted intervention consisting of drug seller training, supply of diagnostics and subsidised medicines, use of treatment algorithms, monthly supervision and community sensitisation was implemented in drug shops in South Western Uganda, to improve paediatric fever management. Focus group discussions and in-depth interviews were conducted with stakeholders (drug sellers, government officials and community health workers) at baseline, midpoint and end-line between September 2013 and September 2015. Using a health market and systems lens, transcripts from the interviews were analysed to identify health system effects associated with the apparent success of the intervention.FindingsStakeholders initially expressed caution and fears about the intervention’s implications for quality, equity and interface with the regulatory framework. Over time, these stakeholders embraced the intervention. Most respondents noted that the intervention had improved drug shop standards, enabled drug shops to embrace patient record keeping, parasite-based treatment of malaria and appropriate medicine use. There was also improved supportive supervision, and better compliance to licensing and other regulatory requirements. Drug seller legitimacy was enhanced from the community and client perspective, leading to improved trust in drug shops.ConclusionThe study showed how effectively using health technologies and the perceived efficacy of medicines contributed to improved legitimacy and trust in drug shops among stakeholders. The study also demonstrated that using a combination of appropriate incentives and consumer empowerment strategies can help harmonise common practices with medicine regulations and safeguard public health, especially in mixed health market contexts.
Exact solutions for scalar field cosmology in f(R) gravity
Authors: Maharaj S. D. , Goswami R. , Chervon S. V. , Nikolaev A. V. 
Published: September 2017

We study scalar field FLRW cosmology in the content of f(R) gravity. Our consideration is restricted to the spatially flat Friedmann universe. We derived the general evolution equations of the model, and showed that the scalar field equation is automatically satisfied for any form of the f(R) function. We also derived representations for kinetic and potential energies, as well as for the acceleration in terms of the Hubble parameter and the form of the f(R) function. Next we found the exact cosmological solutions in modified gravity without specifying the f(R) function. With negligible acceleration of the scalar curvature, we found that the de Sitter inflationary solution is always attained. Also we obtained new solutions with special restrictions on the integration constants. These solutions contain oscillating, accelerating, decelerating and even contracting universes. For further investigation, we selected special cases which can be applied with early or late inflation. We also found exact solutions for the general case for the model with negligible acceleration of the scalar curvature in terms of special Airy functions. Using initial conditions which represent the universe at the present epoch, we determined the constants of integration. This allows for the comparison of the scale factor in the new solutions with that for current stage of the universe evolution in the [Formula: see text]CDM model.
The gas sensing properties of hafnium oxide thin films depending on the annealing environment
Authors: Karaduman Irmak , Acar Selim 
Published: September 2017

The main focus of this study is to investigate the NO2 gas-sensing properties of HfO2 thin films, taking into the account the importance of the annealing environment and temperature. HfO2 films were produced with 10 nm and 20 nm thicknesses by atomic layer deposition (ALD). They were annealed under N2 and O2 environment with rapid thermal annealing system at two different temperatures. It was found that the NO2 responses of annealed in N2 environment were higher than annealed in O2 environment. The response of 10 nm thickness HfO2 thin film was calculated 22% for N2 environment whereas, it was calculated 18% for O2 environment. The highest gas response is obtained for 10 nm thickness of HfO2 thin film annealed in N2 environment. The performance of the HfO2 thin films reveals that the gas responses rely on annealing temperature as well as annealing atmosphere. The linear dependences of the sensitivity were also observed as the NO2 gas concentrations varied from 10 ppm to 30 ppm in logarithmic forms, indicating that HfO2 thin films offer promising potential for future practical applications in monitoring the NO2 gas.
Role of MicroRNA-423-5p in posttranscriptional regulation of the intestinal riboflavin transporter-3
Authors: Lakhan Ram , Subramanian Veedamali S. , Said Hamid M. 
Published: September 2017

Riboflavin (RF) is essential for normal cellular functions and health. Humans obtain RF from exogenous sources via intestinal absorption that involves a highly specific carrier-mediated process. We have recently established that the riboflavin transporter-3 (RFVT3) is vital for the normal intestinal RF uptake process and have characterized certain aspects of its transcriptional regulation. Little is known, however, about how this transporter is regulated at the posttranscriptional level. We address this issue by focusing on the role of microRNAs. Using bioinformatics, we identified two potential interacting miRNAs with the human (h) RFVT3-3′-UTR, and showed (using pmirGLO-hRFVT3-3′-UTR) that the hRFVT3-3′-UTR is, indeed, a target for miRNA effect. Of the two putative miRNAs identified, miR-423-5p was found to be highly expressed in intestinal epithelial cells and that its mimic affected luciferase reporter activity of the pmirGLO-hRFVT3-3′-UTR construct, and also led to inhibition in RF uptake by intestinal epithelial Caco-2 and HuTu-80 cells. Furthermore, cells transfected with mutated seed sequences for miR-423-5p showed an abrogation in inhibitory effect of the miR-423-5p mimic on luciferase activity. While miR-423-5p did not affect the level of expression of the hRFVT3 mRNA, it did lead to a significant inhibition in the level of expression of its protein. Similarly, miR-423-5p was found to affect the level of expression of the mouse RFVT3 in cultured intestinal enteroids. These findings demonstrate, for the first time, that the RFVT3 is a target for posttranscriptional regulation by miRNAs in intestinal epithelial cells and that this regulation has functional consequences on intestinal RF uptake. NEW & NOTEWORTHY Our findings show for the first time that RFVT3 is a target for posttranscriptional regulation by miR-423-5p in intestinal epithelial cells, and this regulation has functional consequences on intestinal riboflavin (RF) uptake process.
Influence of past injurious exercise on fiber type-specific acute anabolic response to resistance exercise in skeletal muscle
Authors: Takagi Ryo , Ogasawara Riki , Takegaki Junya , Tsutaki Arata , Nakazato Koichi , Ishii Naokata 
Published: September 2017

We investigated the influence of past injurious exercise on anabolic response of skeletal muscle fibers to resistance exercise (RE). Wistar rats were divided into exercise (E) and exercise-after-injury (I-E) groups. At age 10 wk, the right gastrocnemius muscle in each rat in the I-E group was subjected to strenuous eccentric contractions. Subsequently, RE was imposed on the same muscle of each rat at 14 wk of age in both groups. Peak joint torque and total force generation per body mass during RE were similar between the groups. Muscle protein synthesis (MPS) in the I-E group was higher than that in the E group 6 h after RE. Furthermore, levels of phospho-p70S6 kinase (Thr389) and phospho-ribosomal protein S6 (phospho-rpS6) (Ser240/244), a downstream target of p70S6 kinase, were higher in the I-E group than in the E group. For the anabolic response in each fiber type, the I-E group showed a higher MPS response in type IIb, IIa, and I fibers and a higher phospho-rpS6 response in type IIx, IIa, and I fibers than the E group. In the I-E group, the relative content of myosin heavy chain (MHC) IIa was higher and that of MHC IIb was lower than those in the E group. In addition, type IIa fibers showed a lower MPS response to RE than type IIb fibers in the I-E group. In conclusion, the past injurious exercise enhanced the MPS and phospho-rpS6 responses in type IIb, IIa, and I fibers and type IIx, IIa, and I fibers, respectively. NEW & NOTEWORTHY Past injurious exercise increased the muscle protein synthesis (MPS) response and mammalian target of rapamycin complex 1 (mTORC1) signaling activation to resistance exercise. In the responses of each fiber type, the past injurious exercise increased the MPS and phosphorylation ribosomal protein (Ser240/244) responses in type IIb, IIa, and I fibers and type IIx, IIa, and I fibers, respectively.
PD-1 Status in CD8+ T Cells Associates with Survival and Anti-PD-1 Therapeutic Outcomes in Head and Neck Cancer
Authors: Kansy Benjamin A. , Concha-Benavente Fernando , Srivastava Raghvendra M. , Jie Hyun-Bae , Shayan Gulidanna , Lei Yu , Moskovitz Jessica , Moy Jennifer , Li Jing , Brandau Sven , Lang Stephan , Schmitt Nicole C. , Freeman Gordon J. , Gooding William E. , Clump David A. , Ferris Robert L. 
Published: September 2017

Abstract
Improved understanding of expression of immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency of PD-1+ TIL has been reported in human papillomavirus (HPV)+ HNC patients, despite the role of PD-1 in T-cell exhaustion. This discordance led us to hypothesize that the extent of PD-1 expression more accurately defines T-cell function and prognostic impact, because PD-1high T cells may be more exhausted than PD-1low T cells and may influence clinical outcome and response to anti-PD-1 immunotherapy. In this study, PD-1 expression was indeed upregulated on HNC patient TIL, and the frequency of these PD-1+ TIL was higher in HPV+ patients (P = 0.006), who nonetheless experienced significantly better clinical outcome. However, PD-1high CD8+ TILs were more frequent in HPV− patients and represented a more dysfunctional subset with compromised IFN-γ secretion. Moreover, HNC patients with higher frequencies of PD-1high CD8+ TIL showed significantly worse disease-free survival and higher hazard ratio for recurrence (P &lt; 0.001), while higher fractions of PD-1low T cells associated with HPV positivity and better outcome. In a murine HPV+ HNC model, anti-PD-1 mAb therapy differentially modulated PD-1high/low populations, and tumor rejection associated with loss of dysfunctional PD-1high CD8+ T cells and a significant increase in PD-1low TIL. Thus, the extent of PD-1 expression on CD8+ TIL provides a potential biomarker for anti-PD-1–based immunotherapy. Cancer Res; 77(22); 6353–64. ©2017 AACR.
Extracellular S100A9 Protein in Bone Marrow Supports Multiple Myeloma Survival by Stimulating Angiogenesis and Cytokine Secretion
Authors: De Veirman Kim , De Beule Nathan , Maes Ken , Menu Eline , De Bruyne Elke , De Raeve Hendrik , Fostier Karel , Moreaux Jérôme , Kassambara Alboukadel , Hose Dirk , Heusschen Roy , Eriksson Helena , Vanderkerken Karin , Van Valckenborgh Els 
Published: September 2017

Abstract
Dysregulated expression of S100 protein family members is associated with cancer proliferation, invasion, angiogenesis, and inflammation. S100A9 induces myeloid-derived suppressor cell (MDSC) accumulation and activity. MDSCs, immunosuppressive cells that contribute to tumor immune escape, are the main producers of S100A9. In this study, we evaluated the role of extracellular S100A9 and the therapeutic relevance of S100A9 inhibition in multiple myeloma (MM), using the immunocompetent murine 5T33MM model. We demonstrated the presence of S100A9 and its receptor TLR4 in both monocytic and granulocytic MDSCs in human and mouse samples. We showed that S100A9 acted as a chemoattractant for MM cells and induced MDSCs to express and secrete inflammatory and pro-myeloma cytokines, including TNFα, IL6, and IL10. Blocking S100A9 interactions in vivo with the small molecule ABR-238901 did not directly affect MDSC accumulation but did reduce IL6 and IL10 cytokine expression by MDSC. ABR-238901 treatment in vivo reduced angiogenesis but had only minor effects on tumor load as single agent (6% reduction). However, ABR-238901 treatment in combination with bortezomib resulted in an increased reduction in tumor load compared with single treatments (50% relative reduction compared with bortezomib alone). Our data suggest that extracellular S100A9 promotes MM and that inhibition of S100A9 may have therapeutic benefit. Cancer Immunol Res; 5(10); 839–46. ©2017 AACR.
Nueva especie de rana bromelícola del género Pristimantis (Amphibia: Craugastoridae), meseta de la Cordillera del Cóndor, Ecuador
Authors: Brito M. Jorge , Almendáriz C. Ana , Batallas R. Diego , Ron Santiago R. 
Published: September 2017

We describe a small frog of the genus Pristimantis inhabiting bromeliads (snout-vent length 20.3‑23.3 mm in females, 16.1‑17.4 mm in males), from a remote sandstone plateau of the Cordillera del Condor, in southeastern Ecuador, with an altitudinal range of 2,045‑2,860 m. A phylogeny based on sequences of DNA (mitochondrial and nuclear genes) supports inclusion in the P. orestes group and suggests an undescribed Pristimantis from the southern slope of eastern Ecuador as the closest taxon. The new species differs from its congeners in Ecuador by having predominantly black dorsal and ventral coloration; comprehensive and robust palmar surface with stubby fingers; presence of a deep and wide groove from the anterior base of finger I to the rear base of the palmar tubercle; subarticular divided tubers, enlarged supernumerary small granules and tubercles. All individuals were found in terrestrial bromeliads. The calls are short, frequency modulated, comprising of a note 5‑15 ms in duration. Insects represented 80% of the diet of the new species.