bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arthrographis kalrae Keratitis Complicated by Endophthalmitis: A Case Report With Literature Review
Authors: Ting Darren Shu Jeng , Mckenna Michael , Sadiq Salman Naveed , Martin Jessica , Mudhar Hardeep S. , Meeney Adam , Patel Trushar 
Published: May 2020

Objectives:
To report the first case of Arthrographis kalrae keratitis complicated by endophthalmitis in the UK and to review the current literature.

Methods:
A case report with literature review.

Results:
A 65-year-old male patient, with a background of treated B-cell lymphoma and herpes simplex virus-related neurotrophic keratopathy, presented with a large infiltrative corneal ulcer in the right eye. The patient was immediately commenced on empirical antifungal treatment in view of the clinical suspicion of fungal keratitis (FK). The initial corneal scrape identified the organism as nonspecific “mold,” and the identity of A. kalrae was subsequently confirmed using matrix-assisted laser/desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS). During the clinical course, the patient received topical, intrastromal, intracameral, and systemic antifungal treatment, repeat therapeutic corneal cross-linking treatment, and three penetrating keratoplasties. Although a temporary improvement was achieved with therapeutic corneal cross-linking treatment, the FK progressed relentlessly and was ultimately complicated by an endophthalmitis despite maximum medical and surgical treatment, eventuating in an enucleation.

Conclusions:

A. kalrae keratitis is an exceptionally rare clinical entity that poses significant therapeutic challenges. MALDI-TOF-MS serves as a useful diagnostic technique in identifying this rare organism. Although the literature suggested that A. kalrae keratitis may sometimes be controlled with antifungal medical treatment alone, this approach was proven to be futile in our immunocompromised patient with pre-existing neurotrophic keratopathy, suggesting that early surgical intervention such as therapeutic keratoplasty may be required in these cases.
Establishing a Geriatric Hip Fracture Program at a Level 1 Community Trauma Center
Authors: O'Mara-Gardner Kristin , Redfern Roberta E. , Bair Jeffrey M. 
Published: May 2020

BACKGROUND:
Traditional care of patients with geriatric hip fracture has been fragmented with patients admitted under various specialty services and to different units within a hospital. This produces inconsistent care and leads to varying outcomes that can be associated with increased length of stay, delays in time from admission to surgery, and higher readmission rates.

PURPOSE:
The purpose of this article is to describe the process taken to establish a successful geriatric hip fracture program (GFP) and the initial results observed in a single institution after its implementation.

METHODS:
All patients 60 years or older, with an osteoporotic hip fracture sustained from a low energy mechanism (defined as a fall from 3-ft height or less), were included in our program. Fracture patterns include femoral neck, intertrochanteric, pertrochanteric, and subtrochanteric femur fractures including displaced, nondisplaced, and periprosthetic fractures. Preprogram data included all patients admitted from January 1, 2012, through December 31, 2014; postprogram data were collected on patients admitted between May 1, 2016, and May 1, 2018.

RESULTS:
Demographic characteristics of the populations were similar. After the GFP was implemented, the proportion of patients who were treated surgically within 24 and 48 hours increased. The average number of hours between admission and surgery significantly reduced from 35.2 to 23.2 hours. Overall length of stay was decreased by 1.8 days and readmission within 30 days of discharge was lower. Reasons for readmission were similar in both timeframes. The rate of inpatient death was similar in the two groups. Mortality within 30 days of surgery appeared somewhat higher in the post-GFP period.

CONCLUSION:
Our program found that, with the utilization of a multidisciplinary approach, we could positively influence the care of patients with geriatric hip fracture through the implementation of evidence-based practice guidelines. In the first 2 years after initiation of the GFP, our institution saw a decrease in time from admission to surgery, length of stay, and blood transfusion requirements.
The correspondence between the structure of the terrestrial mobility network and the emergence of COVID-19 in Brazil
Authors: Freitas Vander L. S. , Konstantyner Thais C. R. O. , Feitosa Jeferson , Sepetauskas Catia S. N. , Santos Leonardo B. L. 
Published: May 2020

BACKGROUNDthe inter-cities mobility network serves as a proxy for the SARS-CoV-2 spreading network in a country.OBJECTIVEto investigate the correspondences between the structure of the mobility network and the emergence of COVID-19 cases in Brazilian cities.METHODSwe adopt the data from the Brazilian Health Ministry and the terrestrial flow of people between cities from the IBGE database in two scales: Brazilian cities without the North region and cities from the Sao Paulo state. Grounded on the complex networks approach, cities are represented as nodes and the flows as edges. Network centrality measures such as strength and degree are ranked and compared to the list of Brazilian cities, ordered according to the day that they confirmed the first case of COVID-19.FINDINGSThe strength presents the best correspondences and the interiorization process of SARS-CoV-2 is captured in the Sao Paulo state when different thresholds are applied to the network flows.MAIN CONCLUSIONSthe strength captures the cities with a higher vulnerability of receiving new cases of COVID-19. Some countryside cities such as Feira de Santana (Bahia state), Ribeirao Preto (Sao Paulo state), and Caruaru (Pernambuco state) have strength comparable to states’ capitals, making them potential super spreaders.Financial supportSão Paulo Research Foundation (FAPESP) Grant Numbers 2015/50122-0, 2018/06205-7 and 2020/06837-3; DFG-IRTG Grant Number 1740/2; CNPq Grant Numbers 420338/2018-7 and 101720/2020-3.
Requirement and functional redundancy of two large ribonucleotide reductase subunit genes for cell cycle, chloroplast biogenesis in tomato
Authors: Gu Mengjun , Liu Yi , Cui Man , Wu Huilan , Ling Hong-Qing 
Published: May 2020

AbstractRibonucleotide reductase (RNR), functioning in thede novosynthesis of dNTPs, is crucial for DNA replication and cell cycle progression. However, the knowledge about the RNR in plants is still limited. In this study, we isolatedylc1(youngleafchlorosis1) mutant, which exhibited many development defects such as dwarf stature, chlorotic young leaf, and smaller fruits. Map-based cloning, complementation, and knocking-out experiments confirmed thatYLC1encodes a large subunit of RNR (SlRNRL1), an enzyme involved in thede novobiosynthesis of dNTPs. Physiological and transcriptomic analyses indicate that SlRNRL1 plays a crucial role in the regulation of cell cycle, chloroplast biogenesis, and photosynthesis in tomato. In addition, we knocked outSlRNRL2(aSlRNRL1homolog) using CRISPR-Cas9 technology in the tomato genome, and found that SlRNRL2, possessing a redundant function with SlRNRL1, played a weak role in the formation of RNR complex due to its low expression intensity. Genetic analysis reveals that SlRNRL1 and SlRNRL2 are essential for tomato growth and development as the double mutantslrnrl1slrnrl2is lethal. This also implies that thede novosynthesis of dNTPs is required for seed development in tomato. Overall, our results provide a new insight for understanding the SlRNRL1 and SlRNRL2 functions and the mechanism ofde novobiosynthesis of dNTPs in plants.
Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
Authors: Ahmad Imtiaz , Alam Mohammud , Saadi Ryan , Mahmud Saborny , Saadi Emily 
Published: May 2020

AbstractImportancePatients in long-term care facilities (LTCF) are at a high-risk of contracting COVID-19 due to advanced age and multiple comorbidities. Without effective treatments, outbreaks in such facilities will become commonplace and will result in severe morbidity and mortality. The effectiveness of doxycycline (DOXY) and hydroxychloroquine (HCQ) combination therapy in high risk COVID-19 patients in longterm care facilities is not yet understood.ObjectiveThe goal of this analysis is to describe outcomes after use of DOXY-HCQ combination in high-risk COVID-19 patients in LTCF.DesignCase-series analysis.SettingThree (3) LTCFs in New York.ParticipantsFrom March 19 to March 30, 2020, fifty-four (54) patients, residents of three (3) LTCFs in New York and diagnosed (confirmed or presumed) with COVID-19, were included in this analysis.ExposureAll patients who were diagnosed (confirmed or presumed) with COVID-19 received DOXY-HCQ combination therapy along with standard of care.Main Outcomes and MeasuresPatients characteristics, clinical recovery, radiological improvements, medication side-effects, hospital transfer, and death were assessed as outcome measures.ResultsA series of fifty-four (54) high-risk patients, who developed a sudden onset of fever, cough, and shortness of breath (SOB) and were diagnosed or presumed to have COVID-19, were started with a combination of DOXY-HCQ and 85% (n=46) patients showed clinical recovery defined as: resolution of fever and SOB, or a return to baseline setting if patients are ventilator-dependent. A total of 11% (n=6) patients were transferred to acute care hospitals due to clinical deterioration and 6% (n=3) patients died in the facilities. Naive Indirect Comparison suggests these data were significantly better outcomes than the data reported in MMWR (reported on March 26, 2020) from a long-term care facility in King County, Washington where 57% patients were hospitalized, and 22% patients died.ConclusionThe clinical experience of this case series indicates DOXY-HCQ treatment in high-risk COVID-19 patients is associated with a reduction in clinical recovery, decreased transfer to hospital and decreased mortality were observed after treatment with DOXY-HCQ.
GWAS of Depression Phenotypes in the Million Veteran Program and Meta-analysis in More than 1.2 Million Participants Yields 178 Independent Risk Loci
Authors: Levey Daniel F. , Stein Murray B. , Wendt Frank R. , Pathak Gita A. , Zhou Hang , Aslan Mihaela , Quaden Rachel , Harrington Kelly M. , Sanacora Gerard , McIntosh Andrew M. , Concato John , Polimanti Renato , Gelernter Joel 
Published: May 2020

ABSTRACTWe report a large meta-analysis of depression using data from the Million Veteran Program (MVP), 23andMe Inc., UK Biobank, and FinnGen; including individuals of European ancestry (n=1,154,267; 340,591 cases) and African ancestry (n=59,600; 25,843 cases). We identified 223 and 233 independent SNPs associated with depression in European ancestry and transancestral analysis, respectively. Genetic correlations within the MVP cohort across electronic health records diagnosis, survey self-report of diagnosis, and a 2-item depression screen exceeded 0.81. Using transcriptome-wide association study (TWAS) we found significant associations for gene expression in several brain regions, including hypothalamus (NEGR1, p=3.19×10−25) and nucleus accumbens (DRD2, p=1.87×10−20). 178 genomic risk loci were fine-mapped to find likely causal variants. We identified likely pathogenicity in these variants and overlapping gene expression for 17 genes from our TWAS, including TRAF3. This study sheds light on the genetic architecture of depression and provides new insight into the interrelatedness of complex psychiatric traits.
Field evaluation of biocontrol agents against black-foot and Petri diseases of grapevine
Authors: del Pilar Martínez-Diz María , Díaz-Losada Emilia , Andrés-Sodupe Marcos , Bujanda Rebeca , Maldonado-González María Mercedes , Ojeda Sonia , Yacoub Amira , Rey Patrice , Gramaje David 
Published: May 2020

ABSTRACTBACKGROUNDBlack-foot and Petri diseases are the main fungal diseases associated with young grapevine decline. Two field experiments were established to evaluate the preventive effect of two potential biocontrol agents (BCAs), i.e.Streptomycessp. E1 + R4 andPythium oligandrumPo37, and three BCA-commercial products containingTrichoderma atrovirideSC1,Trichoderma koningiiTK7 andPseudomonas fluorescens+Bacillus atrophaeuson fungal infection in grafted plants and plant growth parameters.RESULTSThe effectiveness of some BCA in reducing the incidence and severity of both diseases was dependent on the plant part analyzed and the plant age. No single BCA application was able to control both diseases.Streptomycessp. E1+R4 were able to reduce significantly black-foot disease infection whileP. oligandrumPo37 andTrichodermaspp. were able to reduce significantly Petri disease infection. BCA treatments had no effect on the shoot weight, and root weight was significantly lower in all BCA treatments with respect to the control.CONCLUSIONSThe combination of the disease-suppressive activity of two or more beneficial microbes in a biocontrol preparation is required to prevent infection by black-foot and Petri disease fungi in vineyards.
Network reconstruction for trans acting genetic loci using multi-omics data and prior information
Authors: Hawe Johann S. , Saha Ashis , Waldenberger Melanie , Kunze Sonja , Wahl Simone , Müller-Nurasyid Martina , Prokisch Holger , Grallert Harald , Herder Christian , Peters Annette , Strauch Konstantin , Theis Fabian J. , Gieger Christian , Chambers John , Battle Alexis , Heinig Matthias 
Published: May 2020

AbstractBackgroundMolecular multi-omics data provide an in-depth view on biological systems, and their integration is crucial to gain insights in complex regulatory processes. These data can be used to explain disease related genetic variants by linking them to intermediate molecular traits (quantitative trait loci, QTL). Molecular networks regulating cellular processes leave footprints in QTL results as so-calledtrans-QTL hotspots. Reconstructing these networks is a complex endeavor and use of biological prior information has been proposed to alleviate network inference. However, previous efforts were limited in the types of priors used or have only been applied to model systems. In this study, we reconstruct the regulatory networks underlyingtrans-QTL hotspots using human cohort data and data-driven prior information.ResultsWe devised a strategy to integrate QTL with human population scale multi-omics data and comprehensively curated prior information from large-scale biological databases. State-of-the art network inference methods applied to these data and priors were used to recover the regulatory networks underlyingtrans-QTL hotspots. We benchmarked inference methods and showed, that Bayesian strategies using biologically-informed priors outperform methods without prior data in simulated data and show better replication across datasets. Application of our approach to human cohort data highlighted two novel regulatory networks related to schizophrenia and lean body mass for which we generated novel functional hypotheses.ConclusionWe demonstrate, that existing biological knowledge can be leveraged for the integrative analysis of networks underlyingtransassociations to deduce novel hypotheses on cell regulatory mechanisms.
To pool or not to pool: Can we ignore cross-trial variability in FMRI?
Authors: Chen Gang , Padmala Srikanth , Chen Yi , Taylor Paul A , Cox Robert W , Pessoa Luiz 
Published: May 2020

AbstractIn this work, we investigate the importance of explicitly accounting for cross-trial variability in neuroimaging data analysis. To attempt to obtain reliable estimates in a task-based experiment, each condition is usually repeated across many trials. The investigator may be interested in (a) condition-level effects, (b) trial-level effects, or (c) the association of trial-level effects with the corresponding behavior data. The typical strategy for condition-level modeling is to create one regressor per condition at the subject level with the underlying assumption that responses do not change across trials. In this methodology ofcomplete pooling, all cross-trial variability is ignored and dismissed as random noise that is swept under the rug of model residuals. Unfortunately, this framework invalidates the generalizability from the confine of specific trials (e.g., particular faces) to the associated stimulus category (“face”), and may inflate the statistical evidence when the trial sample size is not large enough. Here we propose an adaptive and computationally tractable framework that meshes well with the current two-level pipeline and explicitly accounts for trial-by-trial variability. The trial-level effects are first estimated per subject throughno pooling. To allow generalizing beyond the particular stimulus set employed, the cross-trial variability is modeled at the population level throughpartial poolingin a multilevel model, which permits accurate effect estimation and characterization. Alternatively, trial-level estimates can be used to investigate, for example, brain-behavior associations or correlations between brain regions. Furthermore, our approach allows appropriate accounting for serial correlation, handling outliers, adapting to data skew, and capturing nonlinear brain-behavior relationships. By applying a Bayesian multilevel model framework at the level of regions of interest to an experimental dataset, we show how multiple testing can be addressed and full results reported without arbitrary dichotomization. Our approach revealed important differences compared to the conventional method at the condition level, including how the latter can distort effect magnitude and precision. Notably, in some cases our approach led to increased statistical sensitivity. In summary, our proposed framework provides an effective strategy to capture trial-by-trial responses that should be of interest to a wide community of experimentalists.
Mismatch Negativity Predicts Pattern Separation
Authors: Herman Deena , Baker Stevenson , Cazes Jaime , Alain Claude , Rosenbaum R. Shayna 
Published: May 2020

AbstractWe are so tuned to sensory changes that we can detect novelty within hundreds of milliseconds. To what extent does our capacity to automatically discriminate auditory inputs influence encoding of long-term memories? We recorded mismatch negativity (MMN), an event-related potential (ERP) indexing perceptual discrimination, as participants were presented with sound patterns while watching a muted movie. MMN strength predicted how well naïve listeners separated the previously heard from new micropatterns on a subsequent recognition test, providing evidence that the MMN translates into mnemonic pattern separation. Our investigation is the first to show that our capacity to discriminate auditory inputs, as measured by MMN, gives rise to unique memories.
When do opposites attract? A model uncovering the evolution of disassortative mating
Authors: Maisonneuve Ludovic Claude , Beneteau Thomas , Joron Mathieu , Smadi Charline , Llaurens Violaine 
Published: May 2020

AbstractDisassortative mating is a rare form of mate preference that promotes the persistence of polymorphism. While the evolution of assortative mating, and its consequences on trait variation and speciation have been extensively studied, the conditions enabling the evolution of disassortative mating are still poorly understood. Mate preferences increase the risk of missing mating opportunities, a cost that can be compensated by a greater fitness of offspring. Heterozygote advantage should therefore promote the evolution of disassortative mating, which maximizes the number of heterozygous offspring. From the analysis of a two-locus diploid model, with one locus controlling the mating cue under viability selection and the other locus coding for the level of disassortative preference, we show that heterozygote advantage and negative frequency-dependent viability selection acting at the cue locus promote the fixation of disassortative preferences. The conditions predicted to enable the evolution of disassortative mating in our model match the selection regimes acting on traits subject to disassortative mating behavior in the wild. In sharp contrast with the evolution of assortative preferences, we also show that disassortative mating generates a negative frequency-dependent sexual selection, which in turn disadvantages heterozygotes at the cue locus, limiting the evolution of disassortative preferences. This negative feedback loop could explain why this behavior is rare in natural populations.
Resolving the heterogeneity of diaphragmatic mesenchyme: a novel mouse model of congenital diaphragmatic hernia
Authors: Cleal Louise , Martinez-Estrada Ofelia , Chau You-Ying 
Published: May 2020

AbstractCongenital diaphragmatic hernia (CDH) is a relatively common developmental defect with considerable mortality and morbidity. Diaphragm formation is a complex process, involving several cell types, each with different developmental origins. Due to this complexity, the aetiology of CDH is not well understood. The pleuroperitoneal folds (PPFs) and the post hepatic mesenchymal plate (PHMP) are transient structures that are essential during diaphragm development. Using several mouse models including lineage tracing, we demonstrate the heterogeneous nature of the cells that make up the PPFs. The conditional deletion ofWt1(Wilms’ Tumour gene) in the non-muscle mesenchyme of the PPFs results in CDH. We show that the fusion of the PPFs and the PHMP to form a continuous band of tissue involves migration of cells from both sources. The PPFs of mutant mice fail to fuse with the PHMP and exhibit increased RALDH2 expression. However, no changes in the expression of genes implicated in epithelial-to-mesenchymal transition (EMT) are observed. Additionally, the mutant PPFs lack migrating myoblasts and muscle connective tissue fibroblasts (TCF4+/GATA4+), suggesting possible interactions between these cell types. Our study demonstrates the importance of the non-muscle mesenchyme in diaphragm development.Author SummaryCongenital diaphragmatic hernia (CDH) is a frequent developmental defect and it remains one of the most difficult problems of perinatology. The defect can be repaired by surgery but it is often associated with complications and total mortalities are still high (50-60%). The causes of CDH are largely unknown. Body cavity formation is a carefully regulated process, and diaphragm formation defines the thoracic and abdominal cavities. Connective tissue and muscle fibres are the known major players involved in diaphragm formation. Our current study emphasises another player, the mesenchymal cells. We manipulate the expression of an important developmental regulator,Wt1(Wilms’ tumour gene), in mesenchymal cells in a tissue specific manner using transgenic mouse models. We found that mutant mice can survive till birth, develop diaphragmatic hernia, and die shortly after birth. AblatingWt1in the mesenchymal cells leads to ceased movement, and the failure to form a continuous band of tissue. In our model, disruption of mesenchymal cell movement leads to the attenuation of migration of connective tissue fibroblasts and myoblasts, suggesting possible interactions between these cell types.