bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can an Artificial Intelligence Decision Aid Decrease False-Positive Breast Biopsies?
Authors: Heller Samantha L. , Wegener Melanie , Babb James S. , Gao Yiming 
Published: December 2020

Abstract
This study aimed to evaluate the effect of an artificial intelligence (AI) support system on breast ultrasound diagnostic accuracy.
In this Health Insurance Portability and Accountability Act–compliant, institutional review board–approved retrospective study, 200 lesions (155 benign, 45 malignant) were randomly selected from consecutive ultrasound-guided biopsies (June 2017–January 2019). Two readers, blinded to clinical history and pathology, evaluated lesions with and without an Food and Drug Administration–approved AI software. Lesion features, Breast Imaging Reporting and Data System (BI-RADS) rating (1–5), reader confidence level (1–5), and AI BI-RADS equivalent (1–5) were recorded. Statistical analysis was performed for diagnostic accuracy, negative predictive value, positive predictive value (PPV), sensitivity, and specificity of reader versus AI BI-RADS. Generalized estimating equation analysis was used for reader versus AI accuracy regarding lesion features and AI impact on low-confidence score lesions. Artificial intelligence effect on false-positive biopsy rate was determined. Statistical tests were conducted at a 2-sided 5% significance level.
There was no significant difference in accuracy (73 vs 69.8%), negative predictive value (100% vs 98.5%), PPV (45.5 vs 42.4%), sensitivity (100% vs 96.7%), and specificity (65.2 vs 61.9; P = 0.118–0.409) for AI versus pooled reader assessment. Artificial intelligence was more accurate than readers for irregular shape (74.1% vs 57.4%, P = 0.002) and less accurate for round shape (26.5% vs 50.0%, P = 0.049). Artificial intelligence improved diagnostic accuracy for reader-rated low-confidence lesions with increased PPV (24.7% AI vs 19.3%, P = 0.004) and specificity (57.8% vs 44.6%, P = 0.008).
Artificial intelligence decision support aid may help improve sonographic diagnostic accuracy, particularly in cases with low reader confidence, thereby decreasing false-positives.
Is it Safe to Be Transplanted From Living Donors Who Recovered From COVID-19? Experience of 31 Kidney Transplants in a Multicenter Cohort Study From India
Authors: Kute Vivek B. , Godara Suraj , Guleria Sandeep , Ray Deepak S. , Aziz Feroz , Hegde Umapati , Sharma Ashish , Nayak K.S. , Siddini Vishwanath , Sarkar Piyali , Thukral Sharmila , Mondal Rabi Ranjan Sow , Goswami Jitendra , Patel Himanshu V. , Abraham M. Abi , Pathak Vivek , Anandh Urmila , Jha Pranaw Kumar , Bavikar Suhas , Bonu Ravi Shankar , Gulati Sanjeev , B.T. Anil Kumar , Yadav Dinesh Kumar 
Published: December 2020

Background.There is lack of data on feasibility and safety of kidney transplants from living donors who recovered from COVID-19.Methods.Here, we present a retrospective cohort study of 31 kidney transplant recipients (KTR) from living donors who recovered from polymerase chain reaction confirmed COVID-19 across 19 transplant centers in India from July 3, 2020, to December 5, 2020. We detailed demographics, clinical manifestations, immunosuppression regimen, treatment, and outcomes. Donors with a previous diagnosis of COVID-19 were accepted after documenting 2 negative polymerase chain reaction tests with complete symptom resolution for at least 28 days and significant social distancing for 14 days before surgery.Results.COVID-19 clinical severity in donors ranged from completely asymptomatic (71%, n = 22) to mild infection (29%, n = 9). None progressed to moderate or severe stages of the disease in the entire clinical course of home treatment. Patient and graft survival was 100%, respectively, with acute cellular rejection being reported in 6.4% (n = 2) recipient. All recipients and donors were asymptomatic with normal creatinine at median follow-up of 44 days after surgery without any complications relating to surgery and COVID-19.Conclusions.Our data support safety of proceeding with living donation for asymptomatic individuals with comprehensive donor, recipients screening before surgery, using a combination of clinical, radiologic, and laboratory criteria. It could provide new insights into the management of KTR from living donors who have recovered from COVID-19 in India. To the best of our knowledge, this remains the largest cohort of KTR from living donors who recovered from COVID-19.
Unilateral Isolated Paucisymptomatic Optic Disc Edema
Authors: Hawy Eman , Sharma Rahul A. , Peragallo Jason H. , Dattilo Michael , Newman Nancy J. , Biousse Valérie 
Published: December 2020

Background:
Unilateral isolated optic disc edema (UIODE) represents a challenging clinical presentation that frequently precipitates an extensive diagnostic work-up. Patients without an apparent diagnosis despite appropriate investigations are often categorized as having “papillophlebitis,” an entity that is poorly defined in the existing literature. Our aim was to describe the characteristics of a series of patients with paucisymptomatic UIODE, determine the optimal diagnostic approach to such cases, and clarify the clinical features of presumed papillophlebitis.

Methods:
We retrospectively identified 29 patients with UIODE who were seen by neuro-ophthalmologists at a single center between 2005 and 2019. Each patient presented with isolated, unilateral disc edema that was either entirely asymptomatic or associated with minimal visual symptoms. Patients underwent a comprehensive neuro-ophthalmic evaluation and several ophthalmic and systemic investigations. Data from the initial visit and all subsequent clinical visits were collected, including patient demographics, examination findings, and details of the diagnostic work-up.

Results:
Our 29 patients with UIODE were found to have a variety of underlying diagnoses including unilateral papilledema due to idiopathic intracranial hypertension (10 patients), optic nerve sheath meningioma (5), incipient nonarteritic anterior ischemic neuropathy (4), vitreopapillary traction (3), orbital masses (2), a peripapillary choroidal neovascular membrane (1), and presumed papillophlebitis (4). The duration of disc edema varied considerably based on the etiology, but most patients had favorable visual outcomes.

Conclusions:
A systematic approach to the evaluation of UIODE, combined with long-term follow-up, led to a definite diagnosis in a majority of patients, with only 4 patients presumed to have papillophlebitis, a diagnosis the actual existence of which remains controversial.
Making gene drive biodegradable
Authors: Zapletal Josef , Najmitabrizi Neda , Erraguntla Madhav , Lawley Mark A. , Myles Kevin M. , Adelman Zach N. 
Published: December 2020

Gene drive systems have long been sought to modify mosquito populations and thus combat malaria and dengue. Powerful gene drive systems have been developed in laboratory experiments, but may never be used in practice unless they can be shown to be acceptable through rigorous field-based testing. Such testing is complicated by the anticipated difficulty in removing gene drive transgenes from nature. Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation. Modelling also suggests that unlike gene drive transgenes themselves, self-eliminating transgene approaches are expected to tolerate substantial rates of failure. Thus, self-elimination technology may permit rigorous field-based testing of gene drives by establishing strict time limits on the existence of gene drive transgenes in nature, rendering them essentially biodegradable.
This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.
WolbachiastrainwAlbB maintains high density and dengue inhibition following introduction into a field population ofAedes aegypti
Authors: Ahmad Noor Afizah , Mancini Maria-Vittoria , Ant Thomas H. , Martinez Julien , Kamarul Ghazali M. R. , Nazni Wasi A. , Hoffmann Ary A. , Sinkins Steven P. 
Published: December 2020

Aedes aegyptimosquitoes carrying thewAlbBWolbachiastrain show a reduced capacity to transmit dengue virus.wAlbB has been introduced into wildAe. aegyptipopulations in several field sites in Kuala Lumpur, Malaysia, where it has persisted at high frequency for more than 2 years and significantly reduced dengue incidence. Although these encouraging results indicate thatwAlbB releases can be an effective dengue control strategy, the long-term success depends onwAlbB maintaining high population frequencies and virus transmission inhibition, and both could be compromised byWolbachia–host coevolution in the field. Here,wAlbB-carryingAe. aegypticollected from the field 20 months after the cessation of releases showed no reduction inWolbachiadensity or tissue distribution changes compared to awAlbB laboratory colony. ThewAlbB strain continued to induce complete unidirectional cytoplasmic incompatibility, showed perfect maternal transmission under laboratory conditions, and retained its capacity to inhibit dengue. Additionally, a field-collectedwAlbB line was challenged with Malaysian dengue patient blood, and showed significant blocking of virus dissemination to the salivary glands. These results indicate thatwAlbB continues to inhibit currently circulating strains of dengue in field populations ofAe. aegypti, and provides additional support for the continued scale-up ofWolbachiawAlbB releases for dengue control.This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.
Differential attraction in mosquito–human interactions and implications for disease control
Authors: Martinez Julien , Showering Alicia , Oke Catherine , Jones Robert T. , Logan James G. 
Published: December 2020

Mosquito-borne diseases are a major burden on human health worldwide and their eradication through vector control methods remains challenging. In particular, the success of vector control interventions for targeting diseases such as malaria is under threat, in part due to the evolution of insecticide resistance, while for other diseases effective control solutions are still lacking. The rate at which mosquitoes encounter and bite humans is a key determinant of their capacity for disease transmission. Future progress is strongly reliant on improving our understanding of the mechanisms leading to a mosquito bite. Here, we review the biological factors known to influence the attractiveness of mosquitoes to humans, such as body odour, the skin microbiome, genetics and infection by parasites. We identify the knowledge gaps around the relative contribution of each factor, and the potential links between them, as well as the role of natural selection in shaping vector–host–parasite interactions. Finally, we argue that addressing these questions will contribute to improving current tools and the development of novel interventions for the future.
This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.
The use of molecular xenomonitoring for surveillance of mosquito-borne diseases
Authors: Cameron Mary M. , Ramesh Anita 
Published: December 2020

The scientific community recognizes that molecular xenomonitoring (MX) can allow infected mosquitoes to serve as a proxy for human infection in vector-borne disease surveillance, but developing reliable MX systems for programmatic use has been challenging. The primary aim of this article is to examine the available evidence to recommend how MX can best be used for various purposes. Although much of the literature published within the last 20 years focuses on using MX for lymphatic filariasis elimination, a growing body of evidence supports its use in early warning systems for emerging infectious diseases (EIDs). An MX system design must consider the goal and target (e.g. diseases targeted for elimination versus EIDs), mosquito and pathogen characteristics, and context (e.g. setting and health system). MX is currently used as a ‘supplement’ to human surveillance and will not be considered as a ‘replacement’ until the correlation between pathogen-infection rates in human and mosquito populations is better understood. Establishing such relationships may not be feasible in elimination scenarios, due to increasingly dwindling human infection prevalence after successful control, but may still be possible for EIDs and in integrated disease surveillance systems.
This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.
Assessing the impact of low-technology emanators alongside long-lasting insecticidal nets to control malaria
Authors: Hellewell Joel , Sherrard-Smith Ellie , Ogoma Sheila , Churcher Thomas S. 
Published: December 2020

Malaria control in sub-Saharan Africa relies on the widespread use of long-lasting insecticidal nets (LLINs) or the indoor residual spraying of insecticide. Disease transmission may be maintained even when these indoor interventions are universally used as some mosquitoes will bite in the early morning and evening when people are outside. As countries seek to eliminate malaria, they can target outdoor biting using new vector control tools such as spatial repellent emanators, which emit airborne insecticide to form a protective area around the user. Field data are used to incorporate a low-technology emanator into a mathematical model of malaria transmission to predict its public health impact across a range of scenarios. Targeting outdoor biting by repeatedly distributing emanators alongside LLINs increases the chance of elimination, but the additional benefit depends on the level of anthropophagy in the local mosquito population, emanator effectiveness and the pre-intervention proportion of mosquitoes biting outdoors. High proportions of pyrethroid-resistant mosquitoes diminish LLIN impact because of reduced mosquito mortality. When mosquitoes are highly anthropophagic, this reduced mortality leads to more outdoor biting and a reduced additional benefit of emanators, even if emanators are assumed to retain their effectiveness in the presence of pyrethroid resistance. Different target product profiles are examined, which show the extra epidemiological benefits of spatial repellents that induce mosquito mortality.
This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.
When to retrieve and encode episodic memories: a neural network model of hippocampal-cortical interaction
Authors: Lu Qihong , Hasson Uri , Norman Kenneth A. 
Published: December 2020

AbstractRecent human behavioral and neuroimaging results suggest that people are selective in when they encode and retrieve episodic memories. To explain these findings, we trained a memory-augmented neural network to use its episodic memory to support prediction of upcoming states in an environment where past situations sometimes reoccur. We found that the network learned to retrieve selectively as a function of several factors, including its uncertainty about the upcoming state. Additionally, we found that selectively encoding episodic memories at the end of an event (but not mid-event) led to better subsequent prediction performance. In all of these cases, the benefits of selective retrieval and encoding can be explained in terms of reducing the risk of retrieving irrelevant memories. Overall, these modeling results provide a resource-rational account of why episodic retrieval and encoding should be selective and lead to several testable predictions.
Structural refinement of the auditory brainstem neurons in baboons during perinatal development
Authors: Kim Eun-Jung , Nip Kaila , Blanco Cynthia , Kim Jun Hee 
Published: December 2020

AbstractChildren born prematurely suffer from learning disabilities and exhibit reading, speech, and cognitive difficulties, which are associated with an auditory processing disorder. However, it is unknown whether gestational age at delivery and the unnatural auditory environment in neonatal intensive care units (NICU) collectively affect proper auditory development and neuronal circuitry in premature newborns. We morphologically characterized fetal development of the medial superior olivary nucleus (MSO), an area important for binaural hearing and sound localization, in the auditory brainstem of baboon neonates at different gestational ages. Axonal and synaptic structures and the tonotopic differentiation of ion channels in the MSO underwent profound refinements after hearing onset in the uterus. In preterm baboon neonates, these developmental refinements of the MSO were significantly altered by limited maternal sound inputs from the isolated and unnatural environment in the NICU. Thus, the maternal environment, including auditory stimuli in uterus, is essential for auditory nervous system development during the last trimester of pregnancy and critically affects the anatomic and functional formation of synapses and neural circuitry in the preterm newborn brain.
Bioinformatics Analysis of Key Genes and Pathways for Obesity Associated Type 2 Diabetes Mellitus as a Therapeutic Target
Authors: Vastrad Basavaraj , Tengli Anandkumar , Vastrad Chanabasayya , Kotturshetti Iranna 
Published: December 2020

AbstractObesity associated type 2 diabetes mellitus is one of the most common metabolic disorder worldwide. The prognosis of obesity associated type 2 diabetes mellitus patients has remained poor, though considerable efforts have been made to improve the treatment of this metabolic disorder. Therefore, identifying significant differentially expressed genes (DEGs) associated in metabolic disorder advancement and exploiting them as new biomarkers or potential therapeutic targets for metabolic disorder is highly valuable. Differentially expressed genes (DEGs) were screened out from gene expression omnibus (GEO) dataset (GSE132831) and subjected to GO and REACTOME pathway enrichment analyses. The protein - protein interactions network, module analysis, target gene - miRNA regulatory network and target gene - TF regulatory network were constructed, and the top ten hub genes were selected. The relative expression of hub genes was detected in RT-PCR. Furthermore, diagnostic value of hub genes in obesity associated type 2 diabetes mellitus patients was investigated using the receiver operating characteristic (ROC) analysis. Small molecules were predicted for obesity associated type 2 diabetes mellitus by using molecular docking studies. A total of 872 DEGs, including 439 up regulated genes and 432 down regulated genes were observed. Second, functional enrichment analysis showed that these DEGs are mainly involved in the axon guidance, neutrophil degranulation, plasma membrane bounded cell projection organization and cell activation. The top ten hub genes (MYH9, FLNA, DCTN1, CLTC, ERBB2, TCF4, VIM, LRRK2, IFI16 and CAV1) could be utilized as potential diagnostic indicators for obesity associated type 2 diabetes mellitus. The hub genes were validated in obesity associated type 2 diabetes mellitus. This investigation found effective and reliable molecular biomarkers for diagnosis and prognosis by integrated bioinformatics analysis, suggesting new and key therapeutic targets for obesity associated type 2 diabetes mellitus.
Single-cell characterization of subsolid and solid lesions in the lung adenocarcinoma spectrum
Authors: Yanagawa J. , Tran L.M. , Fung E. , Wallace W.D. , Prosper A.E. , Fishbein G.A. , Shea C. , Hong R. , Liu B. , Salehi-Rad R. , Deng J. , Gower A.C. , Campbell J.D. , Mazzilli S.A. , Beane-Ebel J. , Kadara H. , Lenburg M.E. , Spira A.E. , Aberle D.R. , Krysan K. , Dubinett S.M. 
Published: December 2020

SummaryDetermining the clinical significance of CT scan-detected subsolid pulmonary nodules requires an understanding of the molecular and cellular features that may foreshadow disease progression. We studied the alterations at the transcriptome level in both immune and non-immune cells, utilizing single-cell RNA sequencing, to compare the microenvironment of subsolid, solid, and non-involved lung tissues from surgical resection specimens. This evaluation of early spectrum lung adenocarcinoma reveals a significant decrease in the cytolytic activities of natural killer and natural killer T cells, accompanied by a reduction of effector T cells as well as an increase of CD4+regulatory T cells in subsolid lesions. Characterization of non-immune cells revealed that both cancer-associated alveolar type 2 cells and fibroblasts contribute to the deregulation of the extracellular matrix, potentially affecting immune infiltration in subsolid lesions through ligand-receptor interactions. These findings suggest a decrement of immune surveillance in subsolid lesions.
Deep Template-based Protein Structure Prediction
Authors: Wu Fandi , Xu Jinbo 
Published: December 2020

AbstractMotivationTBM (template-based modeling) is a popular method for protein structure prediction. When very good templates are not available, it is challenging to identify the best templates, build accurate sequence-template alignments and construct 3D models from alignments.ResultsThis paper presents a new method NDThreader (New Deep-learning Threader) to address the challenges of TBM. DNThreader first employs DRNF (deep convolutional residual neural fields), which is an integration of deep ResNet (convolutional residue neural networks) and CRF (conditional random fields), to align a query protein to templates without using any distance information. Then NDThreader uses ADMM (alternating direction method of multipliers) and DRNF to further improve sequence-template alignments by making use of predicted distance potential. Finally NDThreader builds 3D models from a sequence-template alignment by feeding it and sequence co-evolution information into a deep ResNet to predict inter-atom distance distribution, which is then fed into PyRosetta for 3D model construction. Our experimental results on the CASP13 and CAMEO data show that our methods outperform existing ones such as CNFpred, HHpred, DeepThreader and CEthreader. NDThreader was blindly tested in CASP14 as a part of RaptorX server, which obtained the best GDT score among all CASP14 servers on the 58 TBM targets.Availability and Implementationavailable as a part of web server athttp://raptorx.uchicago.eduContactjinboxu@gmail.comSupplementary InformationSupplementary data are available online.
Solubility product constant directs the formation of biomolecular condensates
Authors: Chattaraj Aniruddha , Blinov Michael L. , Loew Leslie M. 
Published: December 2020

AbstractBiomolecular condensates, formed by liquid-liquid phase separation (LLPS), are important cellular structures. Using stochastic network-free kinetic models, we establish a physical-chemical basis for the concentration threshold of heterotypic multivalent molecules required for LLPS. We associate phase separation with a bimodal partitioning of the cluster distribution into small oligomers vs. huge polymers. The simulations reveal that LLPS obeys the solubility product constant (Ksp): the product of monomer concentrations, accounting for ideal stoichiometries, does not exceed a threshold no matter how much additional monomer is added to the system – additional monomer is funneled into large clusters. The Ksp applies over a range of valencies and stoichiometries. However, consistent with the importance of disordered domains for LLPS, removing flexible linker domains funnels valency-matched monomers into a “dimer trap”, and Ksp no longer defines a threshold for large cluster formation. We propose Ksp as a new tool for elucidating biomolecular condensate biophysics.