bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discriminative Subtyping of Lung Cancers from Histopathology Images via Contextual Deep Learning
Authors: Lengerich Benjamin J. , Al-Shedivat Maruan , Alavi Amir , Williams Jennifer , Labbaki Sami , Xing Eric P. 
Published: June 2020

AbstractSummarizing multiple data modalities into a parsimonious cancer “subtype” is difficult because the most informative representation of each patient’s disease is not observed. We propose to model these latent summaries asdiscriminative subtypes: sample representations which induce accurate and interpretable sample-specific models for downstream predictions. In this way, discriminative subtypes, which are shared between data modalities, can be estimated from one data modality and optimized according to the predictions induced in another modality. We apply this approach to lung cancer by training a deep neural network to predict discriminative subtypes from histopathology images, and use these predicted subtypes to generate models which classify adenocarcinoma, squamous cell carcinoma, and healthy tissue based on transcriptomic signatures. In this way, we optimize the latent discriminative subtypes through induced prediction loss, and the discriminative subtypes are interpreted with standard interpretation of transcriptomic predictive models. Our framework achieves state-of-the-art classification accuracy (F1-score of 0.97) and identifies discriminative subtypes which link histopathology images to transcriptomic explanations without requiring pre-specification of morphological patterns or transcriptomic processes.
Meningoencephalitis associated with COVID-19: A systematic review
Authors: Mondal Ritwick , Ganguly Upasana , Deb Shramana , Shome Gourav , Pramanik Subhasish , Bandyopadhyay Deebya , Lahiri Durjoy 
Published: June 2020

AbstractBackground and aimsWith the growing number of COVID-19 cases in recent times, the varied range of presentations is progressively becoming an addressing issue among clinicians. A significant set of patients with extra pulmonary symptoms has been reported worldwide. Neurological involvement in the form of altered mental status, loss of consciousness in considerable amounts has drawn attention of physicians all across the globe. Here we venture out to summarise the clinical profile, investigations and radiological findings among patients with SARS-CoV-2 associated meningoencephalitis in the form of a systematic review, which may aid clinicians in early diagnosis and prognostic evaluation of the disease.MethodologyThis review was carried out based on the existing PRISMA (Preferred Report for Systemic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase and Cochrane library and Preprint servers up till 10th June, 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes “SARS-COV-2”, “COVID-19”, “meningoencephalitis” etc. All peer reviewed, case control, case report, pre print articles satisfying our inclusion criteria were involved in the study. The inclusion prerequisites comprised of confirmed SARS-CoV-2 cases with neurological manifestations, previous cases of SARS-CoV, MERS-CoV with neurological involvement provided all the studies were published in English language. Quantitative data was expressed in mean+/-SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p value of <0.05 considered to be statistically significant.ResultsA total of 43 cases were involved from 24 studies after screening from databases and preprint servers, out of which 29 of them had completed investigation profile and were included in the final analysis. Clincial and Laboratory findings as well as neuroimaging findings (CT, MRI and MRS) revealed consistent presentations towards association of COVID-19 with meningoencephalitis. Epileptogenic pictures were also evident on EEG (electroencephalogram) findings.ConclusionSARS-CoV-2 has been isolated from CSF as well as cerebrum of cases with meningoencephalitis depicting the natural tendency of the virus to invade the central nervous system. Speculations about retrograde olfactory transport or alternative haematogenous spread seem to be correlating with above findings. This review may raise the index of suspicion about COVID-19 among clinicians while attending patients with neurological manifestations.
Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: a systematic review
Authors: Hedermann Gitte , Hedley Paula L , Thagaard Ida N , Krebs Lone , Ekelund Charlotte Kvist , Sørensen Thorkild IA , Christiansen Michael 
Published: June 2020

SummaryCongenital heart defects (CHDs) are the most common congenital malformations and affect neonatal mortality and morbidity. The aetiology of CHDs is complex. Large cohort studies have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia and possibly metabolic syndrome (MetS). The aim of this review is to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia, and MetS, or combinations thereof and CHDs overall as well as by subtype in the offspring. A literature search of PubMed and Embase databases identified 2,076 studies, 30 qualified for inclusion. All but one study investigated the individual metabolic disorders and their association with CHDs. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association with CHDs as well as subtypes of CHDs are needed.
Assessment of respiratory droplet transmission during the ophthalmic slit lamp exam: a particle tracking analysis
Authors: Shah Sahil H. , Garg Anupam K. , Patel Shiv , Yim Wonjun , Jokerst Jesse , Chao Daniel L. 
Published: June 2020

AbstractImportanceThe global COVID-19 pandemic, which began in late 2019, has resulted in a renewed focus on the importance of personal protective equipment (PPE) and other interventions to decrease the spread of infectious diseases. While several ophthalmology organizations have recently released guidance on appropriate PPE for surgical procedures and ophthalmology clinics, there is limited experimental evidence demonstrating the efficacy of the various interventions that have been suggested. In this study, we evaluate high-risk aspects of the slit-lamp exam and the effect of various PPE interventions.ObjectiveTo determine the effectiveness of surgical masks, slit lamp shields, and gloves in decreasing the spread of large droplets in an ophthalmology clinical setting and evaluating high-risk sources of contamination.DesignExperimental cough simulation using a fluorescent surrogate of respiratory droplets during an ophthalmic slit lamp examination.SettingSingle-centerParticipantsPatient SimulationMain outcomes and measure(s)Presence of fluorescent particles in the air near or on slit lamp and simulated slit lamp examiner.ResultsSimulated coughing without a mask or slit lamp shield resulted in widespread dispersion of fluorescent droplets on the model slit lamp examination. Coughing with a mask resulted in the most significant decrease in fluorescent droplets, however, particles were still seen to escape from the top of the mask. Coughing with the slit lamp shield alone blocked the majority of forward particle dispersion; however significant distributions of respiratory droplets were found on the slit lamp joystick as well as table. Coughing with both mask and slit lamp shield resulted in the least dispersion on to the simulated examiner. Scanning electron microscopy demonstrated particle sizes of 3-100μm.Conclusion and relevanceMasking has the greatest effect in limiting spread of respiratory droplets, while slit lamp shields, and gloves also contribute to limiting exposure to respiratory droplets from SARS-CoV-2 during slit lamp examination.Key PointsQuestionHow effective are certain personal protective equipment and interventions in the clinic in preventing respiratory droplet spread?FindingsSimulating patient coughing during the slit lamp exam demonstrated that masking appeared to be the most effective intervention to prevent spread of respiratory droplets. Slit lamp shields and gloves were also effective in decreasing exposure to respiratory droplets.MeaningThis study confirms the importance of masking, slit lamp shields, as well as gloves as important interventions to limit exposure to respiratory droplets from respiratory viruses such as SARS-CoV-2.
Therapeutic role of recurrent ESR1-CCDC170 gene fusions in breast cancer endocrine resistance
Authors: Li Li , Lin Ling , Veeraraghavan Jamunarani , Hu Yiheng , Wang Xian , Lee Sanghoon , Tan Ying , Schiff Rachel , Wang Xiao-Song 
Published: June 2020

AbstractBackgroundEndocrine therapy is the most common treatment for estrogen receptor (ER)-positive breast cancer, but its effectiveness is limited by high rates of primary and acquired resistance. There are likely many genetic causes and recent studies suggest the important role ofESR1mutations and fusions in endocrine resistance. Previously we reported a recurrentESR1fusion calledESR1-CCDC170in 6-8% of the luminal B breast cancers that has a worse clinical outcome after endocrine therapy. Despite being the most frequentESR1fusion, its functional role in endocrine resistance have not been studiedin vivo, and the engaged mechanism and therapeutic relevance remain uncharacterized.MethodsThe endocrine sensitivities of HCC1428 or T47D breast cancer cells following genetic perturbations of ESR1-CCDC170 were assessed using clonogenic assays and/or xenograft mouse models. The underlying mechanisms were investigated by reverse phase protein array, western blotting, immunoprecipitation, and bimolecular fluorescence complementation assays. The sensitivity of ESR1-CCDC170 expressing breast cancer cells to concomitant treatments of tamoxifen and HER/SRC inhibitors was assessed by clonogenic assays.ResultsOur results suggested that differentESR1-CCDC170fusions endow different levels of reduced endocrine sensitivityin vivo, resulting in significant survival disadvantages. Further investigation revealed a novel mechanism that ESR1-CCDC170 binds to HER2/HER3/SRC and activates SRC/PI3K/AKT signaling. Silencing of ESR1-CCDC170 in the fusion-positive cell line, HCC1428, downregulates HER2/HER3, represses pSRC/pAKT, and improves endocrine sensitivity. More important, breast cancer cells expressing ectopic or endogenous ESR1-CCDC170 are highly sensitive to treatment regimens combining endocrine agents with the HER2 inhibitor lapatinib and/or the SRC inhibitor dasatinib.ConclusionESR1-CCDC170 may endow breast cancer cell survival under endocrine therapy via maintaining/activating HER2/HER3/SRC/AKT signaling which implies a potential therapeutic strategy for managing these fusion positive tumors.
Novel reference transcriptomes for the sponges Carteriospongia foliascens and Cliona orientalis and associated algal symbiont Gerakladium endoclionum
Authors: Strehlow Brian W. , Pineda Mari-Carmen , Kenkel Carly D. , Laffy Patrick , Duckworth Alan , Renton Michael , Clode Peta L. , Webster Nicole S 
Published: June 2020

AbstractTranscriptomes from sponges are important resources for studying the stress responses of these ecologically important filter feeders, the interactions between sponges and their symbionts, and the evolutionary history of metazoans. Here, we generated reference transcriptomes for two common and cosmopolitan Indo-Pacific sponge species: Carteriospongia foliascens and Cliona orientalis. We also created a reference transcriptome for the primary symbiont of C. orientalis – Gerakladium endoclionum. To ensure a full repertoire of transcripts were included, clones of each sponge species were exposed to a range of individual stressors: decreased salinity, elevated temperature, elevated suspended sediment concentrations, sediment deposition and light attenuation. RNA extracted from all treatments was pooled for each species, using equal concentrations from each clone. Sequencing of pooled RNA yielded 409 and 418 million raw reads for C. foliascens and C. orientalis holobionts (host and symbionts), respectively. Reads underwent quality trimming before assembly with Trinity. Assemblies were filtered into sponge-specific or, for G. endoclionum, symbiont-specific assemblies. Assemblies for C. foliascens, C. orientalis, and G. endoclionum contained 67,304, 82,895, and 28,670 contigs, respectively. Contigs represented 15,248-37,344 isogroups (∼genes) per assembly, and N50s ranged 1,672-4,355 bp. Gene ortholog analysis verified a high level of completeness and quality for sponge-specific transcriptomes, with an average 93% of core EuKaryotic Orthologous Groups (KOGs) and 98% of single-copy metazoan core gene orthologs identified. The G. endoclionum assembly was partial with only 56% of core KOGs and 32% of single-copy eukaryotic core gene orthologs identified. These reference transcriptomes are a valuable resource for future molecular research aimed at assessing sponge stress responses.
Antibiotics effects on the fecal metabolome in preterm infants
Authors: Patton Laura , Li Nan , Garrett Timothy J. , Ruoss J. Lauren , Russell Jordan T. , de la Cruz Diomel , Bazacliu Catalina , Polin Richard A. , Triplett Eric W. , Neu Josef 
Published: June 2020

AbstractWithin a randomized prospective pilot study of preterm infants born less than 33 weeks gestation, fecal samples were collected weekly and metabolomic analysis was performed. The objective is to evaluate for differences in fecal metabolites in infants exposed to antibiotics vs not exposed to antibiotics in the first 48hours after birth. Significant differences were seen in the antibiotics vs no antibiotics group, including pathways related to vitamin biosynthesis, bile acids, amino acid metabolism and neurotransmitters. Early antibiotic exposure in preterm infants may alter metabolites in the intestinal tract of preterm infants. Broader multi-omic studies that address mechanisms will guide more prudent antibiotic use in this population.
Anin vitrohuman-based fracture gap model – Mimicking the crosstalk between bone and immune cells
Authors: Pfeiffenberger Moritz , Damerau Alexandra , Ponomarev Igor , Bucher Christian H. , Chen Yuling , Barnewitz Dirk , Thöne-Reineke Christa , Hoff Paula , Buttgereit Frank , Gaber Timo , Lang Annemarie 
Published: June 2020

AbstractThe interaction between the bone and immune cells plays a crucial role in bone pathologies such as disturbed fracture healing. After a trauma, the initially formed fracture hematoma in the fracture gap contains all important components (immune/stem cells, mediators) to directly induce bone regeneration and is therefore of great importance but most susceptible to negative influences. Thus, reliablein vitromodels are needed to study the underlying mechanisms and to predict the efficiency of novel therapeutic approaches. Since common bioengineering approaches exclude the immune component, we introduce anin vitro3D fracture gap model which combines scaffold-free bone-like constructs with a fracture hematoma model consisting of human peripheral blood (immune cells) and bone marrow-derived mesenchymal stromal cells. Ourin vitro3D fracture gap model provides all osteogenic cues to induce the initial bone healing processes, which were further promoted by applying the osteoinductive deferoxamine (DFO). Thus, we were able to distinctly mimic processes of the initial fracture phase and demonstrated the importance of including the crosstalk between bone and immune cells.
Dynamic configurations of meiotic hotspot determinants
Authors: Chuang Yu-Chien , Smith Gerald R. 
Published: June 2020

AbstractDuring meiosis, appropriate DNA double-strand break (DSB) and crossover distributions are required for proper homologous chromosome segregation in most species. Linear element proteins (LinEs) ofSchizosaccharomyces pombeare DSB hotspot determinants. Clusters of LinE-bound hotspots form within ∼200 kb chromosomal regions independent of DSB formation. Previous reports showed that LinEs form chromatin-bound, dot-like nuclear foci in nuclear spreads and in fixed cells. Here, we investigated the regulation of LinE configuration and distribution in live cells using super-resolution fluorescence microscopy. In live cells at optimal meiotic temperature (∼25°C), LinEs made long linear forms, not previously reported, in both zygotic and azygotic meiosis and shared other characteristics with the synaptonemal complex in other species. LinE structures appeared around the time of replication, underwent a dotty-to-linear-to-dotty configurational transition, and disassembled before the first meiotic division. DSB formation and repair did not detectably influence LinE structure formation, but failure of DSB formation delayed LinE structure disassembly. Several LinE missense mutations formed dotty but not linear LinE configurations. Our study reveals a second, important configuration of LinEs, which suggests that LinE complexes are involved in regulating meiotic events, such as DSB repair, in addition to their established role in DSB formation.
HLH-30 dependent rewiring of metabolism during starvation inC. elegans
Authors: Dall Kathrine B. , Havelund Jesper F. , Harvald Eva Bang , Witting Michael , Færgeman Nils J. 
Published: June 2020

SummaryOne of the most fundamental challenges for all living organisms is to sense and respond to alternating nutritional conditions in order to adapt their metabolism and physiology to promote survival and achieve balanced growth. Here, we applied metabolomics and lipidomics to examine temporal regulation of metabolism during starvation in wildtypeCaenorhabditis elegansand in animals lacking the transcription factor HLH-30. Our findings show for the first time that starvation alters the abundance of hundreds of metabolites and lipid species in a temporal- and HLH-30-dependent manner. We demonstrate that premature death ofhlh-30animals under starvation can be prevented by supplementation of exogenous fatty acids, and that HLH-30 is required for complete oxidation of long-chain fatty acids. We further show that RNAi-mediated knockdown of the gene encoding carnitine palmitoyl transferase I (cpt-1) only impairs survival of wildtype animals and not ofhlh-30animals. Strikingly, we also find that compromised generation of peroxisomes byprx-5knockdown rendershlh-30animals hypersensitive to starvation, which cannot be rescued by supplementation of exogenous fatty acids. Collectively, our observations show that mitochondrial functions are compromised inhlh-30animals and thathlh-30animals rewire their metabolism to largely depend on functional peroxisomes during starvation, underlining the importance of metabolic plasticity to maintain survival.Abstract Figure
Sustained neural rhythms reveal endogenous oscillations supporting speech perception
Authors: van Bree Sander , Sohoglu Ediz , Davis Matthew H , Zoefel Benedikt 
Published: June 2020

AbstractRhythmic sensory or electrical stimulation will produce rhythmic brain responses. These rhythmic responses are often interpreted as endogenous neural oscillations aligned (or “entrained”) to the stimulus rhythm. However, stimulus-aligned brain responses can also be explained as a sequence of evoked responses, which only appear regular due to the rhythmicity of the stimulus, without necessarily involving underlying neural oscillations. To distinguish evoked responses from true oscillatory activity, we tested whether rhythmic stimulation produces oscillatory responses which continue after the end of the stimulus. Such sustained effects provide evidence for true involvement of neural oscillations. In Experiment 1, we found that rhythmic intelligible, but not unintelligible speech produces oscillatory responses in magnetoencephalography (MEG) which outlast the stimulus at parietal sensors. In Experiment 2, we found that transcranial alternating current stimulation (tACS) leads to rhythmic fluctuations in speech perception outcomes after the end of electrical stimulation. We further report that the phase relation between electroencephalography (EEG) responses and rhythmic intelligible speech can predict the tACS phase that leads to most accurate speech perception. Together, we provide fundamental results for several lines of research – including neural entrainment and tACS – and reveal endogenous neural oscillations as a key underlying principle for speech perception.
Mutation Maker, An Open Source Oligo Design Platform for Protein Engineering
Authors: Hiraga Kaori , Mejzlik Petr , Marcisin Matej , Vostrosablin Nikita , Gromek Anna , Arnold Jakub , Wiewiora Sebastian , Svarba Rastislav , Prihoda David , Clarova Kamila , Klempir Ondrej , Navratil Josef , Tupa Ondrej , Vazquez-Otero Alejandro , Walas Marcin W. , Holy Lukas , Spale Martin , Kotowski Jakub , Dzamba David , Temesi Gergely , Russell Jay H. , Marshall Nicholas M. , Murphy Grant S. , Bitton Danny A. 
Published: June 2020

AbstractProtein engineering is the discipline of developing useful proteins for applications in research, therapeutic and industrial processes by modification of naturally occurring proteins or by invention ofde novoproteins. Modern protein engineering relies on the ability to rapidly generate and screen diverse libraries of mutant proteins. However, design of mutant libraries is typically hampered by scale and complexity, necessitating development of advanced automation and optimization tools that can improve efficiency and accuracy. At present, automated library design tools are functionally limited or not freely available. To address these issues, we developed Mutation Maker, an open source mutagenic oligo design software for large-scale protein engineering experiments. Mutation Maker is not only specifically tailored to multi-site random and directed mutagenesis protocols, but also pioneers bespoke mutagenic oligo design forde novogene synthesis workflows. Enabled by a novel bundle of orchestrated heuristics, optimization, constraint-satisfaction and backtracking algorithms, Mutation Maker offers a versatile toolbox for gene diversification design at industrial scale. Supported byin-silicosimulations and compelling experimental validation data, Mutation Maker oligos produce diverse gene libraries at high success rates irrespective of genes or vectors used. Finally, Mutation Maker was created as an extensible platform on the notion that directed evolution techniques will continue to evolve and revolutionize current and future-oriented applications.