bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of COVID-19 on Neuro-Ophthalmology Office Visits and Adoption of Telemedicine Services
Authors: Moss Heather E. , Ko Melissa W. , Mackay Devin D. , Chauhan Divya , Gutierrez Karen G. , Villegas Natacha C. , Lai Kevin E. 
Published: August 2021

Background:
The COVID-19 public health emergency (PHE) has significantly changed medical practice in the United States, including an increase in the utilization of telemedicine. Here, we characterize change in neuro-ophthalmic care delivery during the early COVID-19 PHE, including a comparison of care delivered via telemedicine and in office.

Methods:
Neuro-ophthalmology outpatient encounters from 3 practices in the United States (4 providers) were studied during the early COVID-19 PHE (March 15, 2020–June 15, 2020) and during the same dates 1 year prior. For unique patient visits, patient demographics, visit types, visit format, and diagnosis were compared between years and between synchronous telehealth and in-office formats for 2020.

Results:
There were 1,276 encounters for 1,167 patients. There were 30% fewer unique patient visits in 2020 vs 2019 (477 vs 670) and 55% fewer in-office visits (299 vs 670). Compared with 2019, encounters in 2020 were more likely to be established, to occur via telemedicine and to relate to an efferent diagnosis. In 2020, synchronous telehealth visits were more likely to be established compared with in-office encounters.

Conclusions:
In the practices studied, a lower volume of neuro-ophthalmic care was delivered during the early COVID-19 public health emergency than in the same period in 2019. The type of care shifted toward established patients with efferent diagnoses and the modality of care shifted toward telemedicine.
Detection of Optic Disc Abnormalities in Color Fundus Photographs Using Deep Learning
Authors: Liu T. Y. Alvin , Wei Jinchi , Zhu Hongxi , Subramanian Prem S. , Myung David , Yi Paul H. , Hui Ferdinand K. , Unberath Mathias , Ting Daniel S. W. , Miller Neil R. 
Published: August 2021

Background:
To date, deep learning–based detection of optic disc abnormalities in color fundus photographs has mostly been limited to the field of glaucoma. However, many life-threatening systemic and neurological conditions can manifest as optic disc abnormalities. In this study, we aimed to extend the application of deep learning (DL) in optic disc analyses to detect a spectrum of nonglaucomatous optic neuropathies.

Methods:
Using transfer learning, we trained a ResNet-152 deep convolutional neural network (DCNN) to distinguish between normal and abnormal optic discs in color fundus photographs (CFPs). Our training data set included 944 deidentified CFPs (abnormal 364; normal 580). Our testing data set included 151 deidentified CFPs (abnormal 71; normal 80). Both the training and testing data sets contained a wide range of optic disc abnormalities, including but not limited to ischemic optic neuropathy, atrophy, compressive optic neuropathy, hereditary optic neuropathy, hypoplasia, papilledema, and toxic optic neuropathy. The standard measures of performance (sensitivity, specificity, and area under the curve of the receiver operating characteristic curve (AUC-ROC)) were used for evaluation.

Results:
During the 10-fold cross-validation test, our DCNN for distinguishing between normal and abnormal optic discs achieved the following mean performance: AUC-ROC 0.99 (95 CI: 0.98–0.99), sensitivity 94% (95 CI: 91%–97%), and specificity 96% (95 CI: 93%–99%). When evaluated against the external testing data set, our model achieved the following mean performance: AUC-ROC 0.87, sensitivity 90%, and specificity 69%.

Conclusion:
In summary, we have developed a deep learning algorithm that is capable of detecting a spectrum of optic disc abnormalities in color fundus photographs, with a focus on neuro-ophthalmological etiologies. As the next step, we plan to validate our algorithm prospectively as a focused screening tool in the emergency department, which if successful could be beneficial because current practice pattern and training predict a shortage of neuro-ophthalmologists and ophthalmologists in general in the near future.
Telemedicine Evaluations in Neuro-Ophthalmology During the COVID-19 Pandemic: Patient and Physician Surveys
Authors: Conway Jenna , Krieger Penina , Hasanaj Lisena , Sun Linus , Scharf Jackson M. , Odel Jeffrey G. , Dinkin Marc J. , Oliveira Cristiano , Mackay Devin D. , Rasool Nailyn , Ko Melissa , Rucker Janet C. , Galetta Steven L. , Balcer Laura J. 
Published: August 2021

Background:
The novel coronavirus 2019 (COVID-19) pandemic has transformed health care. With the need to limit COVID-19 exposures, telemedicine has become an increasingly important format for clinical care. Compared with other fields, neuro-ophthalmology faces unique challenges, given its dependence on physical examination signs that are difficult to elicit outside the office setting. As such, it is imperative to understand both patient and provider experiences to continue to adapt the technology and tailor its application. The purpose of this study is to analyze both neuro-ophthalmology physician and patient satisfaction with virtual health visits during the time of the COVID-19 pandemic.

Methods:
Across three institutions (NYU Langone Health, Indiana University Health, and Columbia University Medical Center), telemedicine surveys were administered to 159 patients. Neuro-ophthalmologists completed 157 surveys; each of these were linked to a single patient visit. Patient surveys consisted of 5 questions regarding visit preparation, satisfaction, challenges, and comfort. The physician survey included 4 questions that focused on ability to gather specific clinical information by history and examination.

Results:
Among 159 patients, 104 (65.4%) reported that they were satisfied with the visit, and 149 (93.7%) indicated that they were comfortable asking questions. Sixty-eight (73.9%) patients found the instructions provided before the visit easy to understand. Potential areas for improvement noted by patients included more detailed preparation instructions and better technology (phone positioning, Internet connection, and software). More than 87% (137/157) of neuro-ophthalmologists surveyed reported having performed an examination that provided enough information for medical decision-making. Some areas of the neuro-ophthalmologic examination were reported to be easy to conduct (range of eye movements, visual acuity, Amsler grids, Ishihara color plates, and pupillary examination). Other components were more difficult (saccades, red desaturation, visual fields, convergence, oscillations, ocular alignment, and smooth pursuit); some were especially challenging (vestibulo-ocular reflex [VOR], VOR suppression, and optokinetic nystagmus). Clinicians noted that virtual health visits were limited by patient preparation, inability to perform certain parts of the examination (funduscopy and pupils), and technological issues.

Conclusions:
Among virtual neuro-ophthalmology visits evaluated, most offer patients with appointments that satisfy their needs. Most physicians in this cohort obtained adequate clinical information for decision-making. Even better technology and instructions may help improve aspects of virtual health visits.
Rare copy number variants in ASTN2 gene in patients with neurodevelopmental disorders
Authors: Bauleo Alessia , Montesanto Alberto , Pace Vincenza , Brando Rossella , De Stefano Laura , Puntorieri Domenica , Cento Luca , Loddo Sara , Calacci Chiara , Novelli Antonio , Falcone Elena 
Published: August 2021

Introduction
In humans the normal development of cortical regions depends on the complex interactions between a number of proteins that promote the migrations of neuronal precursors from germinal zones and assembly into neuronal laminae. ASTN2 is one of the proteins implicated in such a complex process. Recently it has been observed that ASTN2 also regulates the surface expression of multiple synaptic proteins resulting in a modulation of synaptic activity. Several rare copy number variants (CNVs) in ASTN2 gene were identified in patients with neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASD), attention deficit–hyperactivity disorders and intellectual disability.

Methods
By using comparative genomic hybridization array technology, we analyzed the genomic profiles of five patients of three unrelated families with NDDs. Clinical diagnosis of ASD was established according to the Statistical Manual of Mental Disorders, Fifth Edition (APA 2013) criteria.

Results
We identified new rare CNVs encompassing ASTN2 gene in three unrelated families with different clinical phenotypes of NDDs. In particular, we identified a deletion of about 70 Kb encompassing intron 19, a 186 Kb duplication encompassing the sequence between the 5′-end and the first intron of the gene and a 205 Kb deletion encompassing exons 6–11.

Conclusion
The CNVs reported here involve regions not usually disrupted in patients with NDDs with two of them affecting only the expression of the long isoforms. Further studies will be needed to analyze the impact of these CNVs on gene expression regulation and to better understand their impact on the protein function.
Diminishing immune responses against variants of concern in dialysis patients four months after SARS-CoV-2 mRNA vaccination
Authors: Dulovic Alex , Strengert Monika , Ramos Gema Morillas , Becker Matthias , Griesbaum Johanna , Junker Daniel , Lürken Karsten , Beigel Andrea , Wrenger Eike , Lonnemann Gerhard , Cossmann Anne , Stankov Metodi V. , Dopfer-Jablonka Alexandra , Kaiser Philipp D. , Traenkle Bjoern , Rothbauer Ulrich , Krause Gérard , Schneiderhan-Marra Nicole , Behrens Georg M.N. 
Published: August 2021

AbstractPatients undergoing chronic hemodialysis were among the first to receive SARS-CoV-2 vaccinations due to their increased risk for severe COVID-19 disease and high case fatality rates. To date, there have been minimal longitudinal studies in hemodialysis patients to ascertain whether protection offered by vaccination is long-lasting. To assess how surrogates for protection changed over time, we examined both the humoral and cellular response in a previously reported cohort of at-risk hemodialysis patients and healthy donors, four months after their second dose of Pfizer BNT162b2. Compared to three weeks post-second vaccination, both cellular and humoral responses against the original SARS-CoV-2 isolate as well as variants of concern were significantly reduced, with some dialyzed individuals having no B- or T-cell response. Our data strongly support the need for a third booster in hemodialysis patients and potentially other at-risk individuals.
Targeted screening for lung cancer with autoantibodies
Authors: Sullivan Frank M. , Mair Frances S. , Anderson William , Armory Pauline , Briggs Andrew , Chew Cindy , Dorward Alistair , Haughney John , Hogarth Fiona , Kendrick Denise , Littleford Roberta , McConnachie Alex , McCowan Colin , McMeekin Nicola , Patel Manish , Rauchhaus Petra , Ritchie Lewis , Robertson Chris , Robertson John , Robles-Zurita Jose , Sarvesvaran Joseph , Sewell Herbert , Sproule Michael , Taylor Thomas , Treweek Shaun , Vedhara Kavita , Schembri Stuart 
Published: August 2021

AbstractEarlier detection of lung cancer is possible, but difficult and costly to achieve. Screening with Low Dose Computed Tomography (LDCT)scanning has been shown to reduce mortality by 20-25% over the past decade but uptake amongst those most likely to suffer the disease has been slow. Resource constraints and a high false positive rate have also limited adoption of LDCT in many health systems. Targeted screening of people most likely to benefit using a range of biomarkers may be one way to improve the yield and reduce the resource requirements of LDCT. Autoantibodies, which amplify the signal produced by cancer derived proteins, are present in the blood of people mounting an immune response to cancer are a potential way to select those at highest risk. We have followed up 12 208 people enrolled in the ECLS trial for three years and shown that the specificity for early stage (I &II) disease is 90.3% throughout that period. More cancers were detected in the control than the intervention arm of the trial (101V 83). Sensitivity was 77.8% after 6 months and dropped to 46.4% after 3 years. At the end of three years the hazard ratios (95%CI) for All Cause, Cancer Specific and Lung Cancer Mortality was 0.82(0.67-1.01), 0.72(0.54-0.97) and 0.70(0.46-1.08) respectively for those randomised to Early CDT testing. As a range of treatment modalities become increasingly more effective it is even more important to target LDCT on those most likely to have early stage disease. Autoantibody testing may be one method of targeting early detection on those most likely to benefit.
Different adjuvanted pediatric HIV envelope vaccines induced distinct plasma antibody responses despite similar B cell receptor repertoires in infant rhesus macaques
Authors: Berendam Stella J. , Morgan-Asiedu Papa K , Mangan Riley J. , Li Shukhang , Heimsath Holly , Luo Kan , Curtis Alan D. , Eudailey Joshua A. , Fox Christopher B. , Tomai Mark A. , Phillips Bonnie , Itell Hannah L. , Kunz Erika , Hudgens Michael , Cronin Kenneth , Wiehe Kevin , Alam S.Munir , Van Rompay Koen K.A. , De Paris Kristina , Permar Sallie R. , Moody M. Anthony , Fouda Genevieve G. 
Published: August 2021

AbstractDifferent HIV vaccine regimens elicit distinct plasma antibody responses in both human and nonhuman primate models. Previous studies in human and non-human primate infants showed that adjuvants influenced the quality of plasma antibody responses induced by pediatric HIV envelope vaccine regimens. We recently reported that use of the 3M052-SE adjuvant and longer intervals between vaccinations are associated with higher magnitude of antibody responses in infant rhesus macaques. However, the impact of different adjuvants in HIV vaccine regimens on the developing infant B cell receptor (BCR) repertoire has not been studied. This study evaluated whether pediatric HIV envelope vaccine regimens with different adjuvants induced distinct antigen-specific memory B cell repertoires and whether specific immunoglobulin (Ig) immunogenetic characteristics are associated with higher magnitude of plasma antibody responses in vaccinated infant rhesus macaques. We utilized archived preclinical pediatric HIV vaccine studies PBMCs and tissue samples from 19 infant rhesus macaques immunized either with (i) HIV Env protein with a squalene adjuvant, (ii) MVA-HIV and Env protein coadministered using a 3-week interval, (iii) MVA-HIV prime/ protein boost with an extended 6-week interval between immunizations, or (iv) with HIV Env administered with 3M-052-SE adjuvant. Frequencies of vaccine-elicited HIV Env-specific memory B cells from PBMCs and tissues were similar across vaccination groups (frequency range of 0.06-1.72%). There was no association between vaccine-elicited antigen-specific memory B cell frequencies and plasma antibody titer or avidity. Moreover, the epitope specificity and Ig immunogenetic features of vaccine-elicited monoclonal antibodies did not differ between the different vaccine regimens. These data suggest that pediatric HIV envelope vaccine candidates with different adjuvants that previously induced higher magnitude and quality of plasma antibody responses in infant rhesus macaques were not driven by distinct antigen-specific memory BCR repertoires.
Microbial communities in retail draft beers and the biofilms they produce
Authors: Bose Nikhil , Auvil Daniel P. , Moore Erica L. , Moore Sean D. 
Published: August 2021

AbstractIn the beer brewing industry, microbial spoilage presents a consistent threat that must be monitored and controlled to ensure the palatability of a finished product. Many of the predominant beer spoilage microbes have been identified and characterized, but the mechanisms of contamination and persistence remain an open area of study. Post-production, many beers are distributed as kegs that are attached to draft delivery systems in retail settings where ample opportunities for microbial spoilage are present. As such, restaurants and bars can experience substantial costs and downtime for cleaning when beer draft lines become heavily contaminated. Spoilage monitoring on the retail side of the beer industry is often overlooked, yet this arena may represent one of the largest threats to the profitability of a beer if its flavor profile becomes substantially distorted. In this study, we sampled and cultured microbial communities found in beers dispensed from a retail draft system to identify the contaminating bacteria and yeasts. We also evaluated their capability to establish new biofilms in a controlled setting. Among four tested beer types, we identified over a hundred different contaminant bacteria and nearly twenty wild yeasts. The culturing experiments demonstrated that most of these microbes were viable and capable of joining new biofilm communities. From these data, we provide an important starting point for the efficient monitoring of beer spoilage in draft systems and provide suggestions for cleaning protocol improvements that can benefit the retail community.ImportanceBeer production, packaging, and service are each vulnerable to contamination by microbes that metabolize beer chemicals and impart undesirable flavors, which can result in the disposal of entire batches. Therefore, great effort is taken by brewmasters to reduce and monitor contamination during production and packaging. A commonly overlooked quality control stage of a beer supply chain is at the retail service end, where beer kegs supply draft lines in bars and restaurants under non-sterile conditions. We found that retail draft line contamination is rampant and that routine line cleaning methods are insufficient to efficiently suppress beer spoilage. Thus, many customers unknowingly experience spoiled versions of the beers they consume. This study identified the bacteria and yeast that were resident in draft beer samples and also assessed their abilities to colonize tubing material as members of stable biofilm communities.
Lifelong single-cell profiling of cranial neural crest diversification
Authors: Fabian Peter , Tseng Kuo-Chang , Thiruppathy Mathi , Arata Claire , Chen Hung-Jhen , Smeeton Joanna , Nelson Nellie , Crump J. Gage 
Published: August 2021

AbstractThe cranial neural crest generates a huge diversity of derivatives, including the bulk of connective and skeletal tissues of the vertebrate head. How neural crest cells acquire such extraordinary lineage potential remains unresolved. By integrating single-cell transcriptome and chromatin accessibility profiles of cranial neural crest-derived cells across the zebrafish lifetime, we observe region-specific establishment of enhancer accessibility for distinct fates. Neural crest-derived cells rapidly diversify into specialized progenitors, including multipotent skeletal progenitors, stromal cells with a regenerative signature, fibroblasts with a unique metabolic signature linked to skeletal integrity, and gill-specific progenitors generating cell types for respiration. By retrogradely mapping the emergence of lineage-specific chromatin accessibility, we identify a wealth of candidate lineage-priming factors, including a Gata3 regulatory circuit for respiratory cell fates. Rather than multilineage potential being an intrinsic property of cranial neural crest, our findings support progressive and region-specific chromatin remodeling underlying acquisition of diverse neural crest lineage potential.HighlightsSingle-cell transcriptome and chromatin atlas of cranial neural crestProgressive emergence of region-specific cell fate competencyChromatin accessibility mapping identifies candidate lineage regulatorsGata3 function linked to gill-specific respiratory programGraphical Abstract
epiRomics: a multi-omics R package to identify and visualize enhancers
Authors: Mawla Alex M. , Huising Mark O. 
Published: August 2021

AbstractSummaryepiRomics is an R package designed to integrate multi-omics data in order to identify and visualize enhancer regions alongside gene expression and other epigenomic modifications. Regulatory network analysis can be done using combinatory approaches to infer regions of significance such as enhancers, when combining ChIP and histone data. Downstream analysis can identify co-occurrence of these regions of interest with other user-supplied data, such as chromatin availability or gene expression. Finally, this package allows for results to be visualized at high resolution in a stand-alone browser.Availability and ImplementationepiRomics is released under Artistic-2.0 License. The source code and documents are freely available through Github (https://github.com/Huising-Lab/epiRomics).Contactammawla@ucdavis.edu or mhuising@ucdavis.eduSupplementary informationSupplementary data, and methods are available online on biorxiv or Github.
Stromal-cell deletion of STAT3 protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration
Authors: Ajay Amrendra K. , Zhao Li , Vig Shruti , Fujikawa Mai , Thakurela Sudhir , Jadhav Shreyas , Chiu I-Jen , Ding Yan , Ramachandran Krithika , Mithal Arushi , Bhatt Aanal , Chaluvadi Pratyusha , Gupta Manoj K. , Sabbisetti Venkata S. , Waaga-Gasser Ana Maria , Murugaiyan Gopal , Frank David A. , Bonventre Joseph V. , Hsiao Li-Li 
Published: August 2021

SUMMARYSignal transducer and activator of transcription 3 (STAT3) is a key transcription factor implicated in the pathogenesis of kidney fibrosis. Although tubular Stat3 deletion in tubular epithelial cells is known to protect mice from kidney fibrosis, the exact function of STAT3 in stromal cells remains unknown. We utilized stromal-cell Stat3 knock-out (KO) mice, CRISPR and pharmacologic activators and inhibitors of STAT3 to investigate its function in pericyte-like cells. STAT3 is phosphorylated in tubular epithelial cells in acute kidney injury whereas its activation expanded to interstitial cells in chronic kidney disease in mice and humans. Stromal cell-specific deletion of Stat3 protects mice from folic acid- and aristolochic acid-induced kidney fibrosis. Mechanistically, STAT3 directly regulates the inflammatory pathway, differentiation of pericytes into myofibroblasts. Specifically, STAT3 activation leads to an increase in migration and profibrotic signaling in genome-edited pericyte-like cells, 10T1/2. Conversely, Stat3 KO or blocking STAT3 function inhibits detachment, spreading, migration, and profibrotic signaling. Furthermore, STAT3 binds to Collagen1a1 promoter of fibrotic mouse kidneys and in pericyte-like cells. Together, our study identifies a previously unknown function of STAT3 in stromal cells that promotes kidney fibrosis and may have therapeutic value in fibrotic kidney disease.Graphical Abstract