bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Size, Histology, and Survival After Stereotactic Ablative Radiotherapy and Sublobar Resection in Node-negative Non-small Cell Lung Cancer
Authors: Raman Vignesh , Jawitz Oliver K. , Cerullo Marcelo , Voigt Soraya L. , Rhodin Kristen E. , Yang Chi-Fu Jeffrey , D’Amico Thomas A. , Harpole David H. , Kelsey Christopher R. , Tong Betty C. 
Published: January 2021

Background:
Although SABR is increasingly emerging as an alternative to surgery for node-negative non-small cell lung cancer, there is poor understanding of patients who may most benefit SABR compared to surgery.

Objective:
This study examined the relationship between tumor size and the comparative outcomes of SABR and sublobar resection in patients with node-negative non-small cell lung cancer.

Results:
A total of 59,949 patients met study criteria: 19,888 (33%) underwent SABR, 33,052 (55%) wedge resection, and 7009 (12%) segmental resection. In multivariable regression, a significant 3-way interaction was found between histology, tumor size, and type of treatment. After stratification by histology, a significant interaction between tumor size and treatment was preserved for patients with adenocarcinoma and squamous cell carcinoma. Sublobar resection was associated with greater survival compared to SABR for tumor sizes greater than 6 and 8 mm for patients with adenocarcinoma and squamous cell carcinoma, respectively. SABR was associated with similar survival compared to sublobar resection for patients with papillary and large cell histology.

Conclusions:
In this National Cancer Database analysis, sublobar resection was associated with greater survival compared to SABR for lesions >6or 8 mm in patients with adenocarcinoma or squamous cell carcinoma; however, SABR was associated with similar survival compared to sublobar resection in patients with aggressive tumors including papillary and large cell histology. Histologic diagnosis in patients with even small tumors may enable better treatment selection in those who cannot tolerate lobectomy.
A Case of Transient Monocular Vision Loss and Paracentral Acute Middle Maculopathy
Authors: Betsch Devin M. , Mishra Amit V. , Freund Paul R. 
Published: January 2021

Abstract:
A 77-year-old man with multiple cerebrovascular risk factors presented with a history of transient monocular vision loss and residual paracentral visual disturbance in the right eye. Carotid ultrasounds, erythrocyte sedimentation rate, and C-reactive protein were all within normal limits. He was found to have retinal whitening within the macula in the right eye, corresponding to an area of decreased retinal perfusion on optical coherence topography (OCT)-angiography and a hyperreflective middle retina band on spectral domain-OCT. This was consistent with a diagnosis of paracentral acute middle maculopathy (PAMM). PAMM should be considered a part of the differential diagnosis in patients with focal visual disturbances, and OCT studies are recommended as part of the work up as subtle fundus findings may be missed.
Postinfectious Optic Neuritis After Hand–Foot–Mouth Disease
Authors: Barrett Spencer C. , Bhat Nita N. , Bindiganavile Shruthi H. , Lee Andrew G. 
Published: January 2021

Abstract:
A 33-year-old man presented with acute painless loss of vision in his right eye after hand–foot–mouth disease (HFMD). Examination confirmed a right optic neuropathy. Neuroimaging and routine evaluations for alternative causes for an optic neuropathy were negative. He was treated with high dose corticosteroids and made an almost complete visual recovery. Postinfectious optic neuritis has been reported after a vast array of infections including: varicella zoster virus, influenza virus, herpes simplex virus, Epstein–Barr Virus, Lyme disease, and many others. Although Coxsackie virus infections are a known cause of HFMD and have been reported to cause maculopathy, to the best of our knowledge, this is the first reported case of optic neuritis after HFMD in the English language ophthalmic literature.
A Multiple Linear Regression Analysis of Rural-Urban COVID-19 Risk Disparities in Texas
Authors: Luo Amber K. , Zhong Sophia , Sun Charles , Wang Jasmine , White Alexander 
Published: January 2021

AbstractAs the number of COVID-19 cases in the U.S. rises, the differential impact of the pandemic in urban and rural regions becomes more pronounced, and the major factors relating to this difference remain unclear. Using the 254 counties of Texas as units of analysis, we utilized multiple linear regression to investigate the influence of 83 county-level predictor variables including race demographics, age demographics, healthcare and financial status, and prevalence of and mortality rate from COVID-19 risk factors on the incidence rate and case fatality rate from COVID-19 in Texas on September 15, 2020. Here, we report that urban counties experience, on average, 41.1% higher incidence rates from COVID-19 than rural counties and 34.7% lower case fatality rates. Through comparisons between our models, we found that this difference was largely attributable to four major predictor variables: namely, the proportion of elderly residents, African American residents, and Hispanic residents, and the presence of large nursing homes. According to our models, counties with high incidence rates of COVID-19 are predicted to have high proportions of African American residents and Hispanic residents coupled with low proportions of elderly residents. Furthermore, we found that counties with the highest case fatality rates are predicted to have high proportions of elderly residents, obese residents, and Hispanic residents, coupled with low proportions of residents ages 20-39 and residents who report smoking cigarettes. In our study, major variables and their effects on COVID-19 risk are quantified, highlighting the most vulnerable populations and regions of Texas.
Cohesin-mediated loop anchors confine the location of human replication origins
Authors: Emerson Daniel , Zhao Peiyao A , Klein Kyle , Ge Chunmin , Zhou Linda , Sasaki Takayo , Yang Liyan , Venvev Sergey V. , Gibcus Johan H. , Dekker Job , Gilbert David M. , Phillips-Cremins Jennifer E. 
Published: January 2021

AbstractDNA replication occurs through an intricately regulated series of molecular events and is fundamental for genome stability across dividing cells in metazoans. It is currently unknown how the location of replication origins and the timing of their activation is determined in the human genome. Here, we dissect the role for G1 phase topologically associating domains (TADs), subTADs, and loops in the activation of replication initiation zones (IZs). We identify twelve subtypes of self-interacting chromatin domains distinguished by their degree of nesting, the presence of corner dot structures indicative of loops, and their co-localization with A/B compartments. Early replicating IZs localize to boundaries of nested corner-dot TAD/subTADs anchored by high density arrays of co-occupied CTCF+cohesin binding sites with divergently oriented motifs. By contrast, late replicating IZs localize to weak TADs/subTAD boundaries devoid of corner dots and most often anchored by singlet CTCF+cohesin sites. Upon global knock-down of cohesin-mediated loops in G1, early wave focal IZs replicate later in S phase and convert to diffuse placement along the genome. Moreover, IZs in mid-late S phase are delayed to the final minutes before entry into G2 when cohesin-mediated dot-less boundaries are ablated. We also delete a specific loop anchor and observe a sharp local delay of an early wave IZ to replication in late S phase. Our data demonstrate that cohesin-mediated loops at genetically-encoded TAD/subTAD boundaries in G1 phase are an essential determinant of the precise genomic placement of human replication origins in S phase.
Brain connectivity at rest predicts individual differences in normative activity during movie watching
Authors: Gruskin David C. , Patel Gaurav H. 
Published: January 2021

ABSTRACTWhen multiple individuals are exposed to the same sensory event, some are bound to have less typical experiences than others. These atypical experiences are underpinned by atypical stimulus-evoked brain activity, the extent of which is often indexed by intersubject correlation (ISC). Previous research has attributed individual differences in ISC to variation in trait-like behavioral phenotypes. Here, we extend this line of work by showing that an individual’s degree and spatial distribution of ISC are closely related to their brain’s intrinsic functional architecture. Using resting state and movie watching fMRI data from 176 Human Connectome Project participants, we reveal that resting state functional connectivity (RSFC) profiles can be used to predict cortex-wide ISC with considerable accuracy. Similar region-level analyses demonstrate that the amount of ISC a brain region exhibits during movie watching is associated with its connectivity to others at rest, and that the nature of these connectivity-activity relationships varies as a function of the region’s role in sensory information processing. Finally, we show that an individual’s unique spatial distribution of ISC, independent of its magnitude, is also related to their RSFC profile. These findings suggest that the brain’s ability to process complex sensory information is tightly linked to its baseline functional organization and motivate a more comprehensive understanding of individual responses to naturalistic stimuli.
Utilizing Multimodal Imaging to Visualize Potential Mechanism for Sudden Death in Epilepsy
Authors: Mandal Ranajay , Budde Ryan , Lawlor Georgia L. , Irazoqui Pedro 
Published: January 2021

AbstractSudden death in epilepsy, or SUDEP, is a fatal condition that accounts for more than 4000 deaths each year. Limited clinical and preclinical data on sudden death suggests critical contributions from autonomic, cardiac, and respiratory pathways. Recent animal (rat) studies on kainic acid induced seizure models explored a potential mechanism for such sudden and severe cardiorespiratory dysregulation being linked to acid reflux induced laryngospasm. Here, we expand on those previous investigations and utilize a multimodal approach to provide visual evidence of acid reflux-initiated laryngospasm and subsequent fatal cardiorespiratory distress in seizing rats.We used systemic kainic acid to acutely induce seizure activity in Long Evans rats, under urethane anesthesia. We recorded electroencephalography (EEG), electrocardiography (ECG), chest plethysmography and esophageal pH signals during simultaneous fast MRI scans of the rat stomach and esophagus. MRI images, in conjunction with electrophysiology data were used to identify seizure progression, stomach acid movement up the esophagus, cardiorespiratory changes, and sudden death.In all cases of sudden death, esophageal pH recordings alongside MRI images visualized stomach acid movement up the esophagus. Severe cardiac (ST segment elevation), respiratory (intermittent apnea) and brain activity (EEG narrowing due to hypoxia) changes were observed only after acid reached the larynx, which strongly suggests onset of laryngospasm following acid reflux. Additionally, absence of stomach acid in the esophagus of animals that survived acute seizure, provided evidence of a causal relationship between acid reflux and sudden death. The complimentary information coming from electrophysiology and fast MRI scans provided insight into the mechanism of esophageal reflux, laryngospasm, obstructive apnea, and subsequent sudden death in seizing animals. The results carry clinical significance as they outline a potential mechanism that may be relevant to SUDEP in humans.
Using genomic prediction to detect microevolutionary change of a quantitative trait
Authors: Hunter DC , Ashraf B , Bérénos C , Ellis PA , Johnston SE , Wilson AJ , Pilkington JG , Pemberton JM , Slate J 
Published: January 2021

AbstractDetecting microevolutionary responses to natural selection by observing temporal changes in individual breeding values is challenging. The collection of suitable datasets can take many years and disentangling the contributions of the environment and genetics to phenotypic change is not trivial. Furthermore, pedigree-based methods of obtaining individual breeding values have known biases. Here, we apply a genomic prediction approach to estimate breeding values of adult weight in a 35-year dataset of Soay sheep (Ovis aries). During the study period adult body weight decreased, but the underlying genetic component of body weight increased, at a rate that is unlikely to be attributable to genetic drift. Thus cryptic microevolution of greater adult body weight has probably occurred. Using genomic prediction to study microevolution in wild populations can remove the requirement for pedigree data, potentially opening up new study systems for similar research.
Fibronectin-mediated inflammatory signaling through integrin α5 in vascular remodeling
Authors: Budatha Madhusudhan , Zhang Jiasheng , Schwartz Martin A. 
Published: January 2021

AbstractAdhesion of vascular endothelial cells (ECs) to the underlying basement membrane potently modulates EC inflammatory activation. The normal basement membrane proteins laminin and collagen IV attenuate inflammatory signaling in part through integrin α2β1. In contrast, fibronectin, the provisional matrix protein found in injured, remodeling or inflamed vessels, sensitizes ECs to inflammatory stimuli through integrins α5β1and and αvβ3. A chimeric integrin in which the cytoplasmic domain of α5 is replaced with that of α2 pairs with β1 and binds fibronectin but signals like α2β1. Here, we examined mice in which integrin α5 is replaced with the α5/2 chimera, using the transverse aortic constriction (TAC) and partial carotid ligation (PCL) models of vessel remodeling. Following TAC and PCL surgery, WT mice showed increased fibronectin deposition and expression of inflammatory markers, which were strongly attenuated in a5/2 mice. α5/2 mice also showed reduced artery wall hypertrophy in the TAC model and diminished inward remodeling in the PCL model. Acute atherosclerosis after PCL in hyperlipidemic ApoE−/− mice on a high fat diet was dramatically decreased in α5/2 mice. These results underscore the key role for integrin α5 signaling in pathological vascular remodeling and support its potential as a therapeutic target.
Immature olfactory sensory neurons provide behaviourally relevant sensory input to the olfactory bulb
Authors: Huang Jane S. , Kunkhyen Tenzin , Rangel Alexander N. , Brechbill Taryn R. , Gregory Jordan D. , Winson-Bushby Emily D. , Liu Beichen , Avon Jonathan T. , Muggleton Ryan J. , Cheetham Claire E.J. 
Published: January 2021

AbstractPostnatal neurogenesis provides an opportunity to understand how newborn neurons integrate into circuits to restore function. Newborn olfactory sensory neurons (OSNs) wire into highly organized olfactory bulb (OB) circuits throughout life, enabling lifelong plasticity and regeneration. Immature OSNs form functional synapses capable of evoking firing in OB projection neurons but what contribution, if any, they make to odor processing is unknown. Here, we show that immature OSNs provide odor input to the OB, where they form monosynaptic connections with excitatory neurons. Importantly, immature OSNs respond as selectively to odorants as mature OSNs and provide information about high odorant concentrations at which mature OSN responses are already maximal, suggesting that immature and mature OSNs provide distinct odor input streams. Furthermore, mice can successfully perform odor detection and discrimination tasks using sensory input from immature OSNs alone. Together, our findings suggest that immature OSNs play a previously unappreciated role in olfactory-guided behavior.
Evaluating the efficacy of Optoα1AR activation in astrocytes in modulating basal hippocampal synaptic excitation and inhibition
Authors: Courtney Connor D. , Sobieski Courtney , Ramakrishnan Charu , Ingram Robbie J. , Wojnowski Natalia M. , DeFazio R. Anthony , Deisseroth Karl , Christian-Hinman Catherine A. 
Published: January 2021

AbstractAstrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. To investigate this relationship, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we tested AAV8-GFAP-Optoα1AR-eYFP (Optoα1AR), a viral vector to enable activation of Gqsignaling in astrocytes via light-sensitive α1-adrenergic receptors. To determine if stimulating astrocytic Optoα1AR modulates hippocampal synaptic transmission, recordings were made in CA1 pyramidal cells with surrounding astrocytes expressing Optoα1AR, channelrhodopsin (ChR2), or GFP. Both high-frequency (20 Hz, 45-ms light pulses, 5 mW, 5 min) and low-frequency (0.5 Hz, 1-s pulses at increasing 1, 5, and 10 mW intensities, 90 s per intensity) blue light stimulation were tested. 20 Hz Optoα1AR stimulation increased both inhibitory and excitatory postsynaptic current (IPSC and EPSC) frequency, and the mIPSC effect was largely reversible within 20 min. By contrast, low-frequency stimulation of Optoα1AR did not modulate either IPSCs or EPSCs, whereas the same stimulation of astrocytic ChR2 was effective. These data demonstrate that Optoα1AR activation in astrocytes changes synaptic excitation and inhibition in a stimulation-sensitive manner, demonstrating the efficacy and utility of GFAP-Optoα1AR as a tool in studying astrocyte-neuron interactions.
Dissociating the effect of reward uncertainty and timing uncertainty on neural indices of reward prediction errors: A reward positivity (RewP) event-related potential (ERP) study
Authors: Muir Alexandra M. , Eberhard Addison C. , Walker Megan S. , Bennion Angus , South Mikle , Larson Michael J. 
Published: January 2021

AbstractAccurate reward predictions include forecasting bothwhata reward will be andwhena reward will occur. We tested how variations in the certainty of reward outcome and certainty in timing of feedback presentation modulate neural indices of reward prediction errors using the reward positivity (RewP) component of the scalp-recorded brain event-related potential (ERP). In a within-subjects design, seventy-three healthy individuals completed two versions of a cued doors task; one cued the probability of a reward outcome while the other cued the probability of a delay before feedback. Replicating previous results, RewP amplitude was larger for uncertain feedback compared to certain feedback. Additionally, RewP amplitude was differentially associated with uncertainty of presence/absence of reward, but not uncertainty of feedback timing. Findings suggest a dissociation in that RewP amplitude is modulated by reward prediction certainty but is less affected by certainty surrounding timing of feedback.
The female pheromone (Z)-4-undecenal mediates flight attraction and courtship in Drosophila melanogaster
Authors: Borrero-Echeverry Felipe , Solum Marit , Trona Federica , Wallin Erika A. , Bengtsson Marie , Witzgall Peter , Lebreton Sebastien 
Published: January 2021

AbstractSpecific mate communication and recognition underlies reproduction and hence speciation. Mate communication evolves during adaptation to ecological niches and makes use of social signals and habitat cues.Our study provides new insights in Drosophila melanogaster premating olfactory communication, showing that female pheromone (Z)-4-undecenal (Z4-11Al) and male pheromone cVA interact with food odour in a sex-specific manner. Furthermore, Z4-11Al, which mediates upwind flight attraction in both sexes, also elicits courtship in experienced males.Twin variants of the olfactory receptor Or69a are co-expressed in the same olfactory sensory neurons, and feed into the same glomerulus in the antennal lobe. Z4-11Al is perceived via Or69aB, while the food odorant (R)-linalool is a main ligand for the other variant, Or69aA. That Z4-11Al mediates courtship in experienced males, not (R)- linalool, is probably due to courtship learning. Behavioural discrimination is reflected by calcium imaging of the antennal lobe, showing distinct glomerular activation patterns by these two compounds.Male sex pheromone cVA is known to affect male and female courtship at close range, but does not elicit upwind flight attraction as a single compound, in to contrast to Z4-11Al. A blend of cVA and the food odour vinegar attracted females, while a blend of female pheromone Z4-11Al and vinegar attracted males instead.Sex-specific upwind flight attraction to blends of food volatiles and male and female pheromone, respectively, adds a new element to Drosophila olfactory premating communication and is an unambiguous paradigm for identifying the behaviourally active components, towards a more complete concept of food-pheromone odour objects.SummaryThe female-produced, species-specific volatile pheromone of D. melanogaster attracts both sexes from a distance, alone and in concert with food odorants, and elicits courtship in experienced males.
Enhanced detection of nucleotide repeat mRNA with hybridization chain reaction
Authors: Glineburg M. Rebecca , Zhang Yuan , Tank Elizabeth , Barmada Sami , Todd Peter K 
Published: January 2021

ABSTRACTRNAs derived from expanded nucleotide repeats form detectable foci in patient cells and these foci are thought to contribute to disease pathogenesis. The most widely used method for detecting RNA foci is fluorescence in situ hybridization (FISH). However, FISH is prone to low sensitivity and photo-bleaching that can complicate data interpretation. Here we applied hybridization chain reaction (HCR) as an alternative approach to repeat RNA foci detection of GC-rich repeats in two neurodegenerative disorders: GGGGCC (G4C2) hexanucleotide repeat expansions inC9orf72that cause amyotrophic lateral sclerosis and frontotemporal dementia (C9 ALS/FTD) and CGG repeat expansions inFMR1that cause Fragile X-associated tremor/ataxia syndrome. We found that HCR of both G4C2and CGG repeats has comparable specificity to traditional FISH, but is >40x more sensitive and shows repeat-length dependence in its intensity. HCR is better than FISH at detecting both nuclear and cytoplasmic foci in human C9 ALS/FTD fibroblasts, patient iPSC derived neurons, and patient brain samples. We used HCR to determine the impact of integrated stress response (ISR) activation on RNA foci number and distribution. G4C2repeat RNA did not readily co-localize with the stress granule marker G3BP1, but ISR induction increased both the number of detectible nuclear RNA foci and the nuclear/cytoplasmic foci ratio in patient fibroblasts and patient derived neurons. Taken together, these data suggest that HCR can be a useful tool for detecting repeat expansion mRNA in C9 ALS/FTD and other repeat expansion disorders.
Optimized antibody humanization by intra and inter VH-VL binding energy sorting
Authors: Zhong Qiang 
Published: January 2021

ABSTRACTHumanization of non-human derived antibody is necessary to reduce the immunogenicity of antibody drug. In recent years, computer aided antibody humanization became an efficient and rapid routine process. We report here a new computational humanization pipeline which includes CDR grafting onto the crystal structures of homologous antibody and CDR grafted humanized antibody structures. Then, the intra and inter VH-VL binding energies are calculated and sorted for optimized humanized antibody. The resulted humanized antibodies are ranked and compared to experimental dataset, which confirms the validity of humanized antibody design by intra and inter VH-VL binding energy.