bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Kidney Injury After Radiocontrast-Enhanced Computerized Tomography in Hospitalized Patients With Advanced Renal Failure
Authors: Gorelik Yuri , Bloch-Isenberg Natalie , Yaseen Hiba , Heyman Samuel N. , Khamaisi Mogher
Published: February 2020

Background

The overall risk of postcontrast acute kidney injury (PC-AKI) after computerized tomography (CT) is negligible, likely because of the small volume of injected iodinated contrast media required. However, the safety of contrast media–enhanced CT in patients with advanced renal functional impairment, an established major risk factor for PC-AKI, is unknown.

Materials and Methods

This is a retrospective study using large data analysis of hospitalized patients at a single center. Adults undergoing CT or magnetic resonance imaging were included in the study and were stratified by estimated glomerular filtration rate (eGFR) (≤30 or >30 mL/min/1.73 m2) and by either contrast-enhanced or nonenhanced imaging. Only patients with serial determination of creatinine before and after imaging were included. Demographic, clinical, and laboratory data between groups were analyzed and compared using univariate analysis, propensity score matching, and multivariate logistic regression analysis.

Results

A total of 22,319 imaging studies were included. Patients with an eGFR of 30 mL/min/1.73 m2 or lower undergoing contrast-enhanced CT (n = 403) had an increased risk to develop PC-AKI than did similar patients undergoing enhanced or nonenhanced magnetic resonance imaging (n = 96) or nonenhanced CT (n = 1576) or patients undergoing contrast-enhanced CT with a preprocedural eGFR higher than 30 mL/min/1.73 m2 (n = 9173). These findings remained robust after propensity matching for demographic, procedural, and clinical parameters. Multivariate regression analysis of all patients undergoing CT with preimaging eGFR of 30 mL/min or lower (n = 1979) revealed that iodine-based contrast enhancement increased the likelihood of post-CT AKI by 51% (confidence interval, 1.23–2.05).

Conclusion

Although radiocontrast-enhanced CT is considered safe in most hospitalized patients and in ambulatory settings, the risk of PC-AKI remains significant among inpatients with substantial preimaging renal functional impairment. Caution is warranted using iodine-based enhanced CT in hospitalized patients with an eGFR of 30 mL/min/1.73 m2 or lower.
Negative-Pressure Pulmonary Edema After Septoplasty
Authors: Erden Burak , AK Semih , Çiftçi Fatih
Published: February 2020

Negative-pressure pulmonary edema is a rare but life-threatening complication of septoplasty seen in the early-postoperative period. The main cause is laryngospasm; often with hypoxia and hemoptysis. In our case, a 36-year-old septoplasty recipient developed symptoms of hypotension, tachycardia and low oxygen saturation 3 hours after extubation. The patient was diagnosed with negative-pressure pulmonary edema. Treatment was applied with noninvasive positive pressure ventilation and diuretics. It should be noted that negative pressure pulmonary edema may vary in terms of presentation and may not be accompanied by laryngospasm.
Analysis of Severe Fever With Thrombocytopenia Syndrome in Critical Ill Patients in Central China
Authors: Nie Qi , Wang Dawei , Ning Zhijie , Li Tianmin , Tian Xinghan , Bian Pengfei , Ding Kun , Hu Chang , Peng Zhi-Yong
Published: February 2020

Introduction:

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis infected by virus (SFTSV) in central and eastern China, which is associated with high mortality. However, limited clinical data have been reported about this critical illness.

Patients and Methods:

Retrospective cohort study in intensive care unit (ICU) patients with SFTSV infection admitted in 2014 to 2019. Diagnosis was confirmed using reverse transcription polymerase chain reaction on serum samples.

Results:

One hundred sixteen patients with SFTSV infection were included (mean age 63 ± 9 years, 59 [51.3%] males). Non-survivors (43.1%) were older, and had lower Glasgow Coma Score, higher Acute Physiology and Chronic Health Evaluation II, and sequential organ failure assessment score at ICU admission. In addition, non-survivors had more severe respiratory failure (PaO2/FiO2: 208 ± 14 mm Hg vs. 297 ± 15 mm Hg), more frequent shock (25[50%] vs. 7[10.6%]), and required more frequently mechanical ventilation (78% vs. 19.7%; P < 0.001) and vasopressor support (56% vs. 9.1%; P < 0.001). Non-survivors experienced more obvious monocyte loss. After adjustment for potential confounding factors, older age, elevated lactate level, and elevated creatinine level were the independent risk factors for death.

Conclusion:

We provided knowledge about the clinical characteristics of SFTS admitted in ICU. Older age, elevated lactate level, and elevated creatinine level may be useful for identifying patients with poor outcome and intensive medical intervention can be provided for patients as soon as possible to reduce mortality.
Surgical Choice for Different Types of Gallbladder Adenomyomatosis: An Initial Experience of 20 Years Laparoscopic Cholecystectomy
Authors: Pang Liwei , Wu Shuodong , Kong Jing
Published: February 2020

Objectives:

The objective of this study was to compare the difference of clinical biochemical statistics in different types of gallbladder adenomyomatosis (GA). To investigate the different effects of patients between the 3 different types of GA.

Materials and Methods:

Retrospective analysis of the clinical data of the adenomyomatosis patients that come from our hospital between 2010 to 2018. According to the preoperative image (all cases are performed as elective surgery), it could be divided into 3 groups: group A: fundal (localized) type; group B: segmental type; group C: diffuse type. The number of each group is 136, 27, 17. We analyze the biochemical statistics (total bilirubin, direct bilirubin, serum bile acid, alanine aminotransferase, aspartate aminotransferase, cholinesterase, etc.) of the 3 groups to explore the difference in operative mode, operative time and prognosis between these 3 groups.

Results:

(1) In the liver function statistics, aspartate aminotransferase has the statistical significance (F=4.974, P=0.012); (2) And the diffuse adenomyomatosis might have a higher bile acid (F=6.048, P=0.005); (3) The segmental and diffuse adenomyomatosis is easier to be combined with stones (F=19.226, P<0.001); (4) The fundal adenomyomatosis seems to have a better prognosis: fewer hospital stay (F=4.519, P=0.018), fewer drainage time (F=6.575, P=0.004) and fewer complications (χ2=29.429, P<0.001).

Conclusions:

GA is a disease characterized by epithelial proliferation and hypertrophy of the muscles of the gallbladder wall with an outpouching of the mucosa into or through the thickened muscular layer and cannot be regarded as a precancerous lesion based on available evidence. As for asymptomatic GA, conservative treatment is recommended with ultrasound examinations twice a year. The fundal type GA can be treated by partial laparoscopic cholecystectomy. The segmental and diffuse-type should undergo a total laparoscopic cholecystectomy.
Optimization of sample preparation for culture-independent sequencing of Bordetella pertussis
Authors: Fong Winkie , Rockett Rebecca , Timms Verlaine , Sintchenko Vitali
Published: February 2020

Bordetella pertussis

, the aetiological agent of whooping cough, is re-emerging globally despite widespread vaccination.

B. pertussis

is highly infectious and, prior to vaccination programmes, was the leading cause of infant mortality. The WHO estimated that over 600 000 deaths are prevented annually by pertussis vaccination, but

B. pertussis

infection was still responsible for over 63 000 deaths globally in 2013. The re-emergence of

B. pertussis

has been linked to strains with inactive or absent major virulence factors included in vaccines such as pertactin, pertussis toxin and filamentous haemagglutinin. Thus, the molecular surveillance of currently circulating strains is critical in understanding and controlling

B. pertussis

. Such information provides data on strains to inform control measures and the identification of future vaccine antigens. Current surveillance and typing methods for

B. pertussis

rely on the availability of clinical isolates. However, since the 1990s, the majority of pertussis cases have been diagnosed by PCR, where an isolate is not needed. The rapid decline in the availability of

B. pertussis

isolates impacts our ability to monitor this infection. The growing uptake of next-generation sequencing (NGS) has offered the opportunity for culture-independent genome sequencing and typing of this fastidious pathogen. Therefore, the objective of the study was to optimize respiratory sample preparation, independent of culture, in order to type

B. pertussis

using NGS. The study compared commercial depletion kits and specimen-processing methods using selective lysis detergents. The goal was to deplete human DNA, the major obstacle for sequencing a pathogen directly from a clinical sample. Samples spiked with a clinically relevant amount of

B. pertussis

were used to provide comparison between the different methods. Commercial depletion kits including the MolYsis, Qiagen Microbiome and NEBNext Kits were tested. Previously published methods, for Saponin and TritonX-100, were also trialled as a depletion. The ratio of

B. pertussis

to human DNA was determined by real-time PCR for ERV3 and IS481 (as markers of human and

B. pertussis

DNA, respectively), then samples were sequenced using the Illumina NextSeq 500 platform. The number of human and

B. pertussis

sequenced reads were then compared between treatments. The results showed that commercial kits reduced the human DNA present, but also reduced the concentration of target

B. pertussis

. However, selective lysis with Saponin treatment resulted in almost undetectable levels of human DNA, with minimal loss of target

B. pertussis

DNA. Sequencing read depth improved five-fold in reads to

B. pertussis

. Our investigation delivered a potential protocol that will enable the public health laboratory surveillance of

B. pertussis

in the era of culture-independent testing.
Private-public mappings in human prefrontal cortex
Authors: Bang Dan , Ershadmanesh Sara , Nili Hamed , Fleming Stephen M.
Published: February 2020

A core feature of human cognition is an ability to separate private states of mind – what we think or believe – from public actions – what we say or do. This ability is central to navigating social interactions in which different contexts often require different mappings between private states and public actions in order to minimise conflict and facilitate communication. Here we investigated how the human brain supports private-public mappings, using an interactive task which required subjects to adapt how they communicated their confidence about a perceptual decision to the social context. Univariate and multivariate analysis of fMRI data revealed that a private-public distinction is reflected in a medial-lateral division of prefrontal cortex – with lateral frontal pole (FPl) supporting the context-dependent mapping from a private sense of confidence to a public report. The concept of private-public mappings provides a promising framework for understanding flexible social behaviour.
Early reduction in PD-L1 expression predicts faster treatment response in human cutaneous leishmaniasis
Authors: Dey Nidhi S. , Senarathna Sujai , Somaratne Vijani , Madarasinghe Nayani , Seneviratne Bimalka , Forrester Sarah , Oca Marcela Montes De , Reis Luiza Campos , Moulik Srija , Walrad Pegine , Chatterjee Mitali , Goto Hiro , Wickremasinghe Renu , Lagos Dimitris , Kaye Paul M. , Ranasinghe Shalindra
Published: February 2020

Cutaneous leishmaniasis (CL) is a chronic skin disease caused byLeishmaniaparasites and in Sri Lanka, CL is caused byL. donovani.Pentavalent antimonials (e.g. sodium stibogluconate; SSG) are first line drugs for CL, despite protracted and painful treatment regimens. Data from animal models indicate that the effectiveness of SSG requires drug-immune synergy, but mechanistic insight from patients is lacking. We studied whole blood and lesion transcriptomes from CL patients in Sri Lanka at presentation and during SSG treatment. In lesions, we identified differential expression of immune-related genes, including immune checkpoint molecules, after the onset of treatment whereas no differentially expressed genes were identified in whole blood. We confirmed reduced lesional PD-L1 and IDO1 protein expression on treatment in a second validation cohort, using digital spatial profiling and quantitative immunohistochemistry. Dual IHC-FISH revealed significantly higher expression of these immune checkpoint molecules on parasite-infected compared to non-infected lesional CD68+monocytes / macrophages. Crucially, early reduction in PD-L1 but not IDO1 expression was predictive of rate of clinical cure and occurred in parallel with a reduction in parasite load. A multivariate cox proportional hazard model showed that patients with lower PD-L1 expression on treatment were more likely to cure earlier (HR= 4.88). Our data support a model whereby the initial anti-leishmanial activity of antimonial drugs alleviates checkpoint inhibition of T cell immunity, facilitating immune-drug synergism and clinical cure. Our findings demonstrate that PD-L1 expression can be used as an early predictor of clinical response to SSG treatment and support the use of PD-L1 inhibition as adjunct host directed therapy in Sri Lankan CL.
New insights intoTrypanosoma cruzievolution and genotyping based on system-wide protein expression profiles (PhyloQuant)
Authors: Mule Simon Ngao , da Costa Martins Andrè Guillherme , Rosa-Fernandes Livia , de Oliveira Gilberto Santos , Rodrigues Carla Monadeli , Quina Daniel , Rosein Graziella E. , Teixeira Marta Maria Geraldes , Palmisano Giuseppe
Published: February 2020

The etiological agent of Chagas disease,Trypanosoma cruzi, is subdivided into seven genetic subdivisions termed discrete typing units (DTUs), TcI-TcVI and Tcbat. The relevance ofT. cruzigenetic diversity to the variable clinical course of the disease, virulence, pathogenicity, drug resistance, transmission cycles and ecological distribution justifies the concerted efforts towards understanding the population structure ofT. cruzistrains. In this study, we introduce a novel approach termed ‘phyloquant’ to infer the evolutionary relationships and assignment ofT. cruzistrains to their DTUs based on differential protein expression profiles evidenced by bottom up large scale mass spectrometry-based quantitative proteomic features. Mass spectrometry features analyzed using parsimony (MS1, iBAQ and LFQ) showed a close correlation between protein expression andT. cruziDTUs and closely related trypanosome species. Although alternative topologies with minor differences between the three MS features analyzed were demonstrated, we show congruence to well accepted evolutionary relationships ofT. cruziDTUs; in all analyses TcI and Tcbat were sister groups, and the parental nature of genotype TcII and the hybrid genotypes TcV/TcVI were corroborated. Character mapping of genetic distance matrices based on phylogenetics and phyloquant clustering showed statistically significant correlations. We propose the first quantitative shotgun proteomics approach as a complement strategy to the genetic-based assignment ofT. cruzistrains to DTUs and evolutionary inferences. Moreover, this approach allows for the identification of differentially regulated and strain/DTU/species-specific proteins, with potential application in the identification of strain/DTU specific biomarkers and candidate therapeutic targets. In addition, the correlation between multi-gene protein expression and divergence of trypanosome species was evaluated, adding another level to understand the genetic subdivisions amongT. cruziDTUs.
A quantitative framework reveals the ecological drivers of grassland soil microbial community assembly in response to warming
Authors: Ning Daliang , Yuan Mengting , Wu Linwei , Zhang Ya , Guo Xue , Zhou Xishu , Yang Yunfeng , Arkin Adam P. , Firestone Mary K. , Zhou Jizhong
Published: February 2020

Unraveling the drivers controlling community assembly is a central issue in ecology. Selection, dispersal, diversification and drift are conceptually accepted as major community assembly processes. Defining their relative importance in governing biodiversity is compellingly needed, but very challenging. Here, we present a novel framework to quantitativelyinfercommunityassemblymechanisms byphylogenetic bin-based null model analysis (iCAMP). Our results with simulated microbial communities showed that iCAMP had high accuracy (0.93 - 0.99), precision (0.80 - 0.94), sensitivity (0.82 - 0.94), and specificity (0.95 - 0.98), which were 10-160% higher than those from the entire community-based approach. Applying it to grassland microbial communities in response to experimental warming, our analysis showed that homogeneous selection (38%) and “drift” (59%) played dominant roles in controlling grassland soil microbial community assembly. Interestingly, warming enhanced homogeneous selection, but decreased “drift” over time. Warming-enhanced selection was primarily imposed on Bacillales in Firmicutes, which were strengthened by increased drought and reduced plant productivity. This general framework should also be useful for plant and animal ecology.
Mitochondrial Proteostasis Requires Genes Encoded in a Neurodevelopmental Syndrome Locus that are Necessary for Synapse Function
Authors: Gokhale Avanti , Lee Chelsea E. , Zlatic Stephanie A. , Freeman Amanda A. H. , Shearing Nicole , Hartwig Cortnie , Ogunbona Oluwaseun , Bassell Julia L. , Wynne Meghan E. , Werner Erica , Xu Chongchong , Wen Zhexing , Seyfried Nicholas , Bearden Carrie E. , Glausier Jill , Lewis David A. , Faundez Victor
Published: February 2020

Eukaryotic cells maintain proteostasis through mechanisms that require cytoplasmic and mitochondrial translation. Genetic defects affecting cytoplasmic translation perturb synapse development, neurotransmission, and are causative of neurodevelopmental disorders such as Fragile X syndrome. In contrast, there is little indication that mitochondrial proteostasis, either in the form of mitochondrial protein translation and/or degradation, is required for synapse development and function. Here we focus on two genes deleted in a recurrent copy number variation causing neurodevelopmental disorders, the 22q11.2 microdeletion syndrome. We demonstrate that SLC25A1 and MRPL40, two genes present in this microdeleted segment and whose products localize to mitochondria, interact and are necessary for mitochondrial protein translation and proteostasis. OurDrosophilastudies show that mitochondrial ribosome function is necessary for synapse neurodevelopment, function, and behavior. We propose that mitochondrial proteostasis perturbations, either by genetic or environmental factors, are a novel pathogenic mechanism for neurodevelopmental disorders.
Intrinsic growth rules of patients infected, dead and recovered with 2019 novel coronavirus in mainland China
Authors: Han Chuanliang , Liu Yimeng , Yang Saini
Published: February 2020

An outbreak of a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) was first diagnosed in Wuhan, China, in December 2019 and then spread rapidly to other regions. We collected the time series data of the cumulative number of confirmed infected, dead, and cured cases from the health commissions in 31 provinces in mainland China. A descriptive model in a logistic form was formulated to infer the intrinsic epidemic rules of COVID-19, which illustrates robustness spatially and temporally. Our model is robust (R2>0.95) to depict the intrinsic growth rule for the cumulative number of confirmed infected, dead, and cured cases in 31 provinces in mainland China. Furthermore, we compared the intrinsic epidemic rules of COVID-19 in Hubei with that of severe acute respiratory syndrome (SARS) in Beijing, which was obtained from the Ministry of Public Health of China in 2003. We found that the infected case is the earliest to be saturated and has the lowest semi-saturation period compared with deaths and cured cases for both COVID-19 and SARS. All the three types of SARS cases are later to saturate and have longer semi-saturation period than that of COVID-19. Despite the virus caused SARS (SARS-CoV) and the virus caused COVID-19 (SARS-CoV-2) are homologous, the duration of the outbreak would be shorter for COVID-19.
Community-wide seed dispersal distances peak at low levels of specialisation in size-structured networks
Authors: Sorensen Marjorie C. , Schleuning Matthias , Donoso Isabel , Neuschulz Eike Lena , Mueller Thomas
Published: February 2020

Network approaches provide insight into the complex web of interspecific interactions that structure ecological communities. However, because data on the functional outcomes of ecological networks are very rarely available, the effect of network structure on ecosystem functions, such as seed dispersal, is largely unknown. Here, we develop a new approach that is able to link interaction networks to a trait-based seed-dispersal model to estimate community-wide seed dispersal distances. We simulated networks, using a niche model based on size-matching between plants and birds, that varied in the degree of niche partitioning. We found that community-wide dispersal distances were longest when networks had low degrees of niche partitioning. We further found that dispersal distances of plant species with small fruits peaked in models without niche partitioning, whereas dispersal distances of medium and large-fruited plants peaked at low degrees of niche partitioning. Our simulations demonstrate that the degree of niche partitioning between species is an important determinant of the ecological functions derived from ecological networks and that simulation approaches can provide new insights into the relationship between the structural and functional components of ecological networks.
Testing the adaptive value of sporulation in budding yeast using experimental evolution
Authors: Thomasson Kelly M. , Franks Alexander , Teotónio Henrique , Proulx Stephen R.
Published: February 2020

Saccharomycesyeast can grow through mitotic vegetative cell division while they convert resources in their environment into biomass. When cells encounter specific low nutrient environments, sporulation may be initiated and meiotic division produces 4 haploid cells contained inside a protective ascus. The protected spore state does not acquire new resources but is partially protected from desiccation, heat, and caustic chemicals. Because cells cannot both be protected and acquire resources simultaneously, committing to sporulation represents a trade-off between current and future reproduction. Recent work has suggested that one of the major environmental factors that select for the formation of spores is passaging through insect guts, as this also represents a major way that yeasts are vectored to new food sources. We subjected replicate populations of a panel of 5 yeast strains to repeated, predictable passaging through insects by feeding them to fruit flies (Drosopila melanogaster) and then allowing surviving yeast cell growth in defined media for a fixed period of time. We also evolved control populations using the same predictable growth environments but without being exposed to flies. We assayed populations for their sporulation rate, as measured by the percentage of cells that had sporulated after resource depletion. We found that the strains varied in their ancestral sporulation rate such that domesticated strains had lower sporulation. During evolution, all strains evolved increased sporulation in response to passaging through flies, but domesticated strains evolved to lower final levels of sporulation. We also found that exposure to flies led to an evolved change in the timing of the sporulation response relative to controls, with a more rapid shift to sporulation, and that wild-derived strains showed a more extreme response. We conclude that strains that have lost the ability to access genetic variation for total sporulation rate and the ability to respond to cues in the environment that favor sporulation due to genetic canalization during domestication.
Convergent losses of TLR5 suggest altered extracellular flagellin detection in four mammalian lineages
Authors: Sharma Virag , Walther Felix , Hecker Nikolai , Stuckas Heiko , Hiller Michael
Published: February 2020

Toll-like receptors (TLRs) play an important role for the innate immune system by detecting pathogen-associated molecular patterns. TLR5 encodes the major extracellular receptor for bacterial flagellin and frequently evolves under positive selection, consistent with coevolutionary arms races between the host and pathogens. Furthermore, TLR5 is inactivated in several vertebrates and a TLR5 stop codon polymorphism is widespread in human populations. Here, we analyzed the genomes of 120 mammals and discovered that TLR5 is convergently lost in four independent lineages, comprising guinea pigs, Yangtze river dolphin, pinnipeds, and pangolins. Validated inactivating mutations, absence of protein-coding transcript expression, and relaxed selection on the TLR5 remnants confirm these losses. PCR analysis further confirmed the loss of TLR5 in the pinniped stem lineage. Finally, we show that TLR11, encoding a second extracellular flagellin receptor, is also absent in these four lineages. Independent losses of TLR5 and TLR11 suggests that a major pathway for detecting flagellated bacteria is not essential for different mammals and predicts an impaired capacity to sense extracellular flagellin
Estimation of risk factors for COVID-19 mortality - preliminary results
Authors: Caramelo F , Ferreira N , Oliveiros B
Published: February 2020

Since late December 2019 a new epidemic outbreak has emerged from Whuhan, China. Rapidly the new coronavirus has spread worldwide. China CDC has reported results of a descriptive exploratory analysis of all cases diagnosed until the 11th February 2020, presenting the epidemiologic curves and geo-temporal spread of COVID-19 along with case fatality rate according to some baseline characteristics, such as age, gender and several well-established high prevalence comorbidities. Despite this, we intend to increase even further the predictive value of that manuscript by presenting the odds ratio for mortality due to COVID-19 adjusted for the presence of those comorbidities and baseline characteristics such as age and gender. Besides, we present a way to determine the risk of each particular patient, given his characteristics.

We found that age is the variable that presents higher risk of COVID-19 mortality, where 60 or older patients have an OR = 18.8161 (CI95%[7.1997; 41.5517]). Regarding comorbidities, cardiovascular disease appears to be the riskiest (OR= 12.8328 CI95%[10.2736; 15.8643], along with chronic respiratory disease (OR=7.7925 CI95%[5.5446; 10.4319]). Males are more likely to die from COVID-19 (OR=1.8518 (CI95%[1.5996; 2.1270]). Some limitations such as the lack of information about the correct prevalence of gender per age or about comorbidities per age and gender or the assumption of independence between risk factors are expected to have a small impact on results. A final point of paramount importance is that the equation presented here can be used to determine the probability of dying from COVID-19 for a particular patient, given its age interval, gender and comorbidities associated.
Non-existent ClinicalTrials.gov identifiers in abstracts indexed by PubMed
Authors: Carlisle Benjamin Gregory
Published: February 2020

Prospective registration plays an important role in ensuring the transparency and reliability of clinical trials. Preregistration of clinical trials has been required by the ICMJE since 2005 and mandated by law for most clinical trial types since 2007. It is one of the roles of peer reviewers of a clinical trial publication to confirm that there is concordance between the registry entry and the submitted publication. On October 22, 2019, abstracts for all articles indexed by PubMed with publication type “Clinical Trial” and a publication date after January 1, 2003 were downloaded. Clinical trial registry identifiers were automatically extracted and tested for the existence of a corresponding entry on ClinicalTrials.gov. Among 38,001 published clinical trial registry numbers, 215 (0.6%) do not correspond to a legitimate clinical trial registry entry. While there is a small proportion of non-existent NCT numbers in our sample, even a single non-existent NCT number in a publication represents a failure on the part of journals who publish clinical trials to systematically ensure that reviewers always check clinical trial registry entries for concordance with the text submitted for publication. These results cast doubt on how frequently editors and reviewers evaluate clinical trial reports in light of their corresponding registry entries.
Multidimensional Analysis of Bronchoalveolar Lavage Cytokines and Mast Cell Proteases Reveals Interferon-γ as a Key Biomarker in Equine Asthma Syndrome
Authors: Woodrow Jane S. , Hines Melissa , Sommardahl Carla , Flatland Bente , Davis Kaori U. , Lo Yancy , Wang Zhiping , Sheats Mary Katherine , Lennon Elizabeth M.
Published: February 2020

Naturally-occurring equine asthma is an inflammatory lung disease characterized by chronic, partially reversible airway obstruction, pulmonary remodeling and lower airway inflammation. The cytokine profiles that distinguish asthma groups or subtypes in horses have not been systematically classified, and mast cell phenotypes, which, in human asthma, correlate with asthma type, lung function, and response to therapy, have not been well-described in horses. The purpose of this study was to: (1) compare mast cell protease mRNA expression between healthy and asthmatic horses, (2) analyze the cytokine profile present in BALF of currently defined equine asthma groups, and (3) use these data to evaluate potential biomarkers of defined asthma groups. Mast cell protease gene expression and select cytokine gene expression in cells isolated from BALF, and BALF multiplex cytokine assays were performed. Multidimensional analysis demonstrated that IFNγ differentiates severe from moderate asthma, and that TNFα and CXCL8 are key biomarkers of equine asthma subtype. Expression of chymase mRNA, a mast cell-specific protease, was significantly decreased in horses with mastocytic asthma. These results will help further define EAS immunopathology, which could improve understanding and definitions of asthma groups, while also potentially identify novel therapeutic strategies.
A Rad51-Independent Pathway Promotes Single-Strand Template Repair in Gene Editing
Authors: Gallagher Danielle N. , Pham Nhung , Tsai Annie M. , Janto Abigail N. , Choi Jihyun , Ira Grzegorz , Haber James E.
Published: February 2020

The Rad51/RecA family of recombinases perform a critical function in typical repair of double-strand breaks (DSBs): strand invasion of a resected DSB end into a homologous double-stranded DNA (dsDNA) template sequence to facilitate repair. However, repair of a DSB using single stranded DNA (ssDNA) as a template, a common method of CRISPR/Cas9-mediated gene editing, is Rad51-independent. We have analyzed the genetic requirements for these Rad51-independent events inSaccharomyces cerevisiaein two different assays. Gene editing events were carried out either by creating a DSB with the site-specific HO endonuclease and repairing the DSB with 80-nt single-stranded oligonucleotides (ssODNs) or by using a bacterial retron system that produces ssDNA templatesin vivoin combination with DSBs created by Cas9. We show that single strand template repair (SSTR), is dependent on Rad52, Rad59, Srs2 and the Mre11-Rad50-Xrs2 (MRX) complex, but not Rad51, Rad54 or Rad55. Srs2 acts to prevent overloading of Rad51 on the ssDNA filament, whereas Rad59 appears to alleviate the inhibition of Rad51 on Rad52’s strand annealing activity; thus, deletion ofRAD51suppresses both thesrs2Δ andrad59Δ phenotypes. This same suppression byrad51Δ ofrad59Δ is found in another DSB repair pathway, single strand annealing (SSA). In contrast, gene targeting using an 80-bp dsDNA template of the same sequence is Rad51-dependent. We also examined SSTR events in which the ssODN carried several mismatches. In the absence of the mismatch repair protein, Msh2, we found that the fate of mismatches carried on the ssDNA template are very different at the 3’ end, which can anneal directly to the resected DSB end, compared to the 5’ end. We also find that DNA polymerase Polδ’s 3’ to 5’ proofreading activity frequently excises a mismatch close to the 3’ end of the template, similar to its removal of heterologies close to the 3’ invading end of the DSB. We further report that SSTR is accompanied by a 600-fold increase in mutations in a region adjacent to the sequences directly undergoing repair. These DNA polymerase ζ-dependent mutations may compromise the accuracy of gene editing.
Transcriptome analysis of somatic cell populations in theDrosophilatestis links metabolism and stemness
Authors: Hof-Michel Silvana , Bökel Christian
Published: February 2020

Due to its simple cellular architecture and genetic tractability the fly testis was one of the first model systems in which stem cell - niche interactions were studied at the molecular level. However, to date there is no comprehensive information on the endogenous, cell type specific transcription profiles associated with either stem cell or differentiated states. Focusing on the somatic lineage we have therefore isolated CySCs, differentiated CyCs, hub cells, and stem cell-like tumour cells overexpressing Zfh1, and have mapped their transcriptomes by RNAseq.

Here we report i) that the different somatic cell populations show extensive, genome wide differences in transcription levels, in particular associated with energy metabolism and innate immune signalling, ii) that differential activation of multiple signalling pathways renders Zfh1 overexpressing tumour cells unsuitable for use as a stem cell model, and iii) that the transcriptome data could be successfully used for identifying genes with stem cell specific expression patterns and for predicting aspects of stem cell physiology whose relevance for stem cell function could be validated in preliminary experiments.

The present data set should therefore facilitate future research on the interaction of stem cells with their niche using the highly successful fly testis model system.
A disulfide constrains the ToxR periplasmic domain structure, altering its interactions with ToxS and bile-salts
Authors: Midgett Charles R , Swindell Rachel A , Pellegrini Maria , Kull F Jon
Published: February 2020

ToxR is a transmembrane transcription factor that, together with its integral membrane periplasmic binding partner ToxS, is conserved across theVibriofamily. In some pathogenicVibrios, includingV. parahaemolyticusandV. cholerae, ToxR is required for bile resistance and virulence, and ToxR is fully activated and protected from degradation by ToxS. ToxS achieves this in part by ensuring formation of an intra-chain disulfide bond in the C-terminal periplasmic domain of ToxR (dbToxRp). In this study, biochemical analysis showed dbToxRp to have a higher affinity for the ToxS periplasmic domain than the non-disulfide bonded conformation. Analysis of our dbToxRp crystal structure showed this is due to disulfide bond stabilization. Furthermore, dbToxRp is structurally homologous to theV. parahaemolyticusVtrA periplasmic domain. These results highlight the critical structural role of disulfide bond in ToxR and along with VtrA define a domain fold involved in environmental sensing conserved across theVibriofamily.
Dynamics as a cause for the nanoscale organization of the genome
Authors: Barth R. , Fourel G. , Shaban H. A.
Published: February 2020

Chromatin ‘blobs’ were recently identified by live super-resolution imaging as pervasive, but transient and dynamic structural entities consisting of a few associating nucleosomes. The origin and functional implications of these blobs are, however, unknown. Following these findings, we explore whether causal relationships exist between parameters characterizing the chromatin blob dynamics and structure, by adapting a framework for spatio-temporal Granger-causality inference. Our analysis reveals that chromatin dynamics is a key determinant of both blob area and local density. However, such causality can only be demonstrated in small areas (10 – 20%) of the nucleus, highlighting that chromatin dynamics and structure at the nanoscale is dominated by stochasticity. Pixels for which the inter-blob distance can be effectively demonstrated to depend on chromatin dynamics appears as clump in the nucleus, and display both a higher blob density and higher local dynamics as compared with the rest of the nucleus. Furthermore, we show that the theory of active semiflexible polymers can be invoked to provide potential mechanisms leading to the organization of chromatin into blobs. Based on active motion-inducing effectors, this framework qualitatively recapitulates experimental observations and predicts that chromatin blobs might be formed stochastically by a collapse of local polymer segments consisting of a few nucleosomes. Our results represent a first step towards elucidating the mechanisms that govern the dynamic and stochastic organization of chromatin in a cell nucleus.
Data-driven polymer model for mechanistic exploration of diploid genome organization
Authors: Qi Yifeng , Reyes Alejandro , Johnstone Sarah E. , Aryee Martin J. , Bernstein Bradley E. , Zhang Bin
Published: February 2020

Chromosomes are positioned non-randomly inside the nucleus to coordinate with their transcriptional activity. The molecular mechanisms that dictate the global genome organization and the nuclear localization of individual chromosomes are not fully understood. We introduce a polymer model to study the organization of the diploid human genome: it is data-driven as all parameters can be derived from Hi-C data; it is also a mechanistic model since the energy function is explicitly written out based on a few biologically motivated hypotheses. These two features distinguish the model from existing approaches and make it useful both for reconstructing genome structures and for exploring the principles of genome organization. We carried out extensive validations to show that simulated genome structures reproduce a wide variety of experimental measurements, including chromosome radial positions and spatial distances between homologous pairs. Detailed mechanistic investigations support the importance of both specific inter-chromosomal interactions and centromere clustering for chromosome positioning. We anticipate the polymer model, when combined with Hi-C experiments, to be a powerful tool for investigating large scale rearrangements in genome structure upon cell differentiation and tumor progression.
Serendipity: Werner's argument that the `two-only forms' (green and violet) of [CoCl2(en)2]+salts demanded his octahedral model was correct. True?
Authors: Bernal Ivan , Lalancette Roger A.
Published: February 2020

Chemists of the late 19th century, including Alfred Werner, prepared salts containing either green or violet cations of composition [CoCl2(en)2]+(en is ethylenediamine, C2H8N2); we now refer to these astrans-dichloro andcis-dichloro species. We have discovered a third salt,purplein color, containing cations of the same elemental composition and whose asymmetric unit composition is [CoCl2(en)2]2Cl2·3H2O, in which the cobalt cations are acis:transdichloro pair. Such a discovery would undermine Werner's argument thatif only two forms can be prepared, his octahedral theory was proven. Probably because his students never examined their crystals under a microscope, they failed to observe the `third' species, thereby ruining Werner's argument since he relied strictly on color to identify them. That was fortunate since our purple salt would have led him to abandon, or certainly delay, his momentous discovery. Our crystals consist of a 1:1 mixture of thecisandtranscations, thereby sharing the same elemental analysis and conductivity as the single salts, but not their crystal structure, inasmuch as X-ray diffraction had not even been discovered then. Serendipitously, our discovery would have been a great boon to his theoretical acumen, while his `two-color' argument may have doomed him.
Novel K/Mn phosphate hydrates, K2Mn3(H2O)2[P2O7]2 and KMn(H2O)2[Al2(PO4)3]: hydrothermal synthesis and crystal chemistry
Authors: Kiriukhina Galina V. , Yakubovich Olga V. , Shvanskaya Larisa V. , Kochetkova Ekaterina M. , Dimitrova Olga V. , Volkov Anatoliy S. , Simonov Sergey V.
Published: February 2020

Two novel K/Mn phosphate hydrates, namely, dipotassium trimanganese dipyrophosphate dihydrate, K2Mn3(H2O)2[P2O7]2, (I), and potassium manganese dialuminium triphosphate dihydrate, KMn(H2O)2[Al2(PO4)3], (II), were obtained in the form of single crystals during a single hydrothermal synthesis experiment. Their crystal structures were studied by X-ray diffraction. Both new compounds are members of the morphotropic series of phosphates with the following formulae: A
2
M
3(H2O)2[P2O7]2, where A = K, NH4, Rb or Na and M = Mn, Fe, Co or Ni, and AM
2+(H2O)2[M
3+
2(PO4)3], where A = Cs, Rb, K, NH4 or (H3O); M
2+ = Mn, Fe, Co or Ni; and M
3+ = Al, Ga or Fe. A detailed crystal chemical analysis revealed correlations between the unit-cell parameters of the members of the series, their structural features and the sizes of the cations. It has been shown that a mixed type anionic framework is formed in (II) by aluminophosphate [(AlO2)2(PO4)2]∞ layers, with a cationic topology similar to the Si/Al-topology of the crystal structures of feldspars. A study of the magnetic susceptibility of (II) demonstrates a paramagnetic behaviour of the compound.
Borates or phosphates? That is the question
Authors: Contreras-García J. , Izquierdo-Ruiz F. , Marqués M. , Manjón F. J.
Published: February 2020

Chemical nomenclature is perceived to be a closed topic. However, this work shows that the identification of polyanionic groups is still ambiguous and so is the nomenclature for some ternary compounds. Two examples, boron phosphate (BPO4) and boron arsenate (BAsO4), which were assigned to the large phosphate and arsenate families, respectively, nearly a century ago, are explored. The analyses show that these two compounds should be renamed phosphorus borate (PBO4) and arsenic borate (AsBO4). Beyond epistemology, this has pleasing consequences at several levels for the predictive character of chemistry. It paves the way for future work on the possible syntheses of SbBO4and BiBO4, and it also renders previous structure field maps completely predictive, allowing us to foresee the structure and phase transitions of NbBO4and TaBO4. Overall, this work demonstrates that quantum mechanics calculations can contribute to the improvement of current chemical nomenclature. Such revisitation is necessary to classify compounds and understand their properties, leading to the main final aim of a chemist: predicting new compounds, their structures and their transformations.
Crystal structure analysis of ethyl 3-(4-chlorophenyl)-1,6-dimethyl-4-methylsulfanyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
Authors: Rao H. Surya Prakash , Gunasundari Ramalingam , Muthukumaran Jayaraman
Published: February 2020

In the title compound, C18H18ClN3O2S, the dihedral angle between the fused pyrazole and pyridine rings is 3.81 (9)°. The benzene ring forms dihedral angles of 35.08 (10) and 36.26 (9)° with the pyrazole and pyridine rings, respectively. In the crystal, weak C—H...O hydrogen bonds connect molecules along [100].
What drives consumer demand for rice fragrance? Evidence from South and Southeast Asia
Authors: Bairagi Subir , Demont Matty , Custodio Marie Claire , Ynion Jhoanne
Published: February 2020

Purpose

The purpose of this paper is to analyze geographic heterogeneity of consumer preferences for intrinsic quality attributes of rice in South and Southeast Asia and the drivers of demand for these attributes, with a particular focus on rice fragrance and the role of gender.

Design/methodology/approach

Stated-preference surveys were conducted with 4,231 urban and rural consumers in 37 cities across seven countries (Bangladesh, India, Cambodia, Indonesia, the Philippines, Thailand, and Vietnam) during 2013–2014 and analyzed through a rank-ordered logistic regression with incomplete ranking choice data.

Findings

Preferences for rice attributes are found to be significantly heterogeneous among consumers in South and Southeast Asia. Urban Thai consumers tend to prioritize appearance and cooking characteristics over taste and nutritional benefits, relative to all other surveyed consumers. In contrast with South Asian consumers, Southeast Asian consumers have largely adopted Thai preferences for rice texture and fragrance, a trend that was earlier coined “Jasminization.” We find that demand for rice fragrance is mainly driven by women, educated consumers, large families, families spending a lower share of their food expenditures on rice, and consumers in Southeast Asia (particularly the Philippines and Cambodia).

Originality/value

Little is known about geographic heterogeneity, drivers, and the role of gender in demand for rice fragrance. This paper fills these knowledge gaps. Our findings suggest that the more women are empowered in grocery decision-making, the more demand for aromatic rice is expected to rise. These insights can assist market-driven and gender-responsive rice breeding programs in simultaneously enhancing rice farmers' livelihoods and gender equity.
The challenge of integrating operational knowledge in building and ship design
Authors: Rasmussen Helle Lohmann
Published: February 2020

Purpose

For optimising long-term building operations, building clients need to enable integration of operational knowledge in the design process of new buildings. This study aims to investigate and compare how operational knowledge is integrated into the design of buildings and large ships, focussing on the roles affiliation and the competences of the client’s project manager play.

Design/methodology/approach

A cross-sectional qualitative methodology with multiple case studies (five cases) was used. In addition, ten expert interviews and two validation focus group interviews were conducted. Case studies included in-depth interviews, document analysis and observations.

Findings

The study showed that organisational affiliation, focus and competences of the client’s project management play an important role in how much effort and resources go into ensuring integration of operational knowledge in the design process. In the ship cases, projects managers’ highest concerns were operations. Yet, the fewest procedures and tools to integrate operational knowledge in design were found implemented in these cases. Contrastingly, in the building cases, where operations were not the main matter of concern of project management, a large number of procedures and tools to integrate operational knowledge in design were implemented.

Originality/value

To the best of the author’s knowledge, this research is the first to compare how integration of operational knowledge is taking place in the design process of buildings and large ships and identifying what these industries can learn from each other. Furthermore, it adds to the limited research on operations in large ship design.