bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraoperative Fluorescence With Second Window Indocyanine Green Enhances Visualization During Vestibular Schwannoma Surgery
Authors: Peng Kevin A. , Lekovic Gregory P. 
Published: November 2021

Objective:
To investigate the utility of the so-called “second window” of indocyanine green (ICG) as a near-infrared fluorescent dye for intraoperative visualization.

Patients:
Three patients who underwent surgical resection of vestibular schwannoma (two retrosigmoid and one middle fossa approach).

Intervention(s):
Patients underwent intravenous infusion of ICG at a mean dose of 4.8 mg/kg at a mean of 15.3 hours before surgical incision. Once tumor dissection began, near-infrared fluorescence was used alongside conventional operative microscopy to visualize tumor tissue.

Main Outcome Measure(s):
Ability to distinguish tumor tissue from adjacent nerves.

Results:
Intraoperative fluorescence allowed for enhanced visualization of the tumor-nerve plane in all patients. However, the effect varied among patients, and the effect faded with increasing surgical time.

Conclusions:
ICG, a well-tolerated cyanine dye, demonstrates late fluorescence hours after administration secondary to diffusion into tumor as well as normal tissues (the so-called “second window” of fluorescence). Its fluorescence in the near-infrared spectrum is a promising adjunct for enhancing visualization of tumor planes during vestibular schwannoma surgery.
Brief Report: Rebound HIV Viremia With Meningoencephalitis After Antiretroviral Therapy Interruption After Allogeneic Bone Marrow Transplant
Authors: Capoferri Adam A. , Redd Andrew D. , Gocke Christopher D. , Clark Laura R. , Quinn Thomas C. , Ambinder Richard F. , Durand Christine M. 
Published: November 2021

Background:
Allogeneic bone marrow transplant (alloBMT) in people living with HIV can lead to the undetectable levels of HIV reservoirs in blood, even using highly sensitive assays. However, with antiretroviral therapy (ART) interruption, rebound of HIV viremia occurs. The source of this rebound viremia is of interest in HIV cure strategies.

Methods:
Within a trial of alloBMT in individuals with hematologic malignancies and HIV (ClinicalTrials.gov, NCT01836068), one recipient self-interrupted ART after achieving >99.5% host cell replacement in peripheral blood by day 147 and developed severe acute retroviral syndrome with meningoencephalitis at 156 days post alloBMT. We isolated replication-competent HIV using a quantitative viral outgrowth assay at 100 and 25 days before alloBMT and from the same time points before alloBMT for HIV DNA and cell-associated RNA from peripheral blood mononuclear cells and resting memory CD4+ T cells. We isolated HIV RNA in plasma and cerebrospinal fluid (CSF) at viral rebound. We sequenced the RT-region of pol and performed neighbor-joining phylogenetic reconstruction.

Results:
Phylogenetic analysis revealed an identical viral sequence at both pre-alloBMT time points accounting for 9 of 34 sequences (26%) of the sampled HIV reservoir. This sequence population grouped with viral rebound sequences from plasma and CSF with high sequence homology.

Discussion:
Despite >99.5% replacement of host cells in peripheral blood, ART interruption led to HIV viral rebound in plasma and CSF. Furthermore, the rebound virus matched replication-competent virus from resting memory CD4+ T cells before alloBMT. This case underscores that HIV-infected recipient cells can persist after alloBMT and that latent replication-competent virus can reestablish infection.
Transcriptome analysis of SARS-CoV-2 naïve and recovered individuals vaccinated with inactivated vaccine
Authors: Zhang Yuwei , Guo Xingyu , Li Cunbao , Kou Zengqiang , Lin Lanfang , Yao Mingxiao , Pang Bo , Zhang Xiaomei , Duan Qing , Tian Xueying , Xing Yufang , Jiang Xiaolin 
Published: November 2021

AbstractThe urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited. Herein, we performed serum IgG antibody detection and transcriptomics analysis on 20 SARS-CoV-2 naïve individuals who received multiple doses of inactivated vaccine and 5 SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine. Our research revealed the important role of many innate immune pathways after vaccination, identified a significant correlation with the third dose of booster vaccine and proteasome-related genes, and found that SARS-CoV-2 recovered individuals can produces a strong immune response to a single dose of inactivated vaccine. These results help us understand the reaction mechanism of the host’s molecular immune system to the inactivated vaccine, and provide a basis for the choice of vaccination strategy.
Monaural and binaural masking release with speech-like stimuli
Authors: Kim Hyojin , Ratkute Viktorija , Epp Bastian 
Published: November 2021

ABSTRACTThe relevance of masking release by comodulation and interaural phase difference (IPD) for speech perception is still unclear. We used speech-like stimuli to link spectro-temporal properties of formants with masking release. The stimuli comprised a tone and three masker bands centered at formant frequencies F1, F2, and F3 derived from a consonant-vowel (/gu/, /fu/, and /pu/). The target was a diotic or dichotic frequency-modulated tone following F2 trajectories. Results showed no statistically significant comodulation masking release (CMR), while the binaural masking level difference (BMLD) was comparable to previous findings. The data suggest that factors other than comodulation may play a dominant role in grouping frequency components in speech.
Cellular and Synaptic Diversity of Layer 2-3 Pyramidal Neurons in Human Individuals
Authors: Planert Henrike , Mittermaier Franz Xaver , Grosser Sabine , Fidzinski Pawel , Schneider Ulf Christoph , Radbruch Helena , Onken Julia , Holtkamp Martin , Schmitz Dietmar , Alle Henrik , Vida Imre , Geiger Jörg Rolf Paul , Peng Yangfan 
Published: November 2021

SummaryUnderstanding the functional principles of the human brain requires deep insight into the neuronal and network physiology. To what extent such principles of cellular physiology and synaptic interactions are common across different human individuals is unknown. We characterized the physiology of ~1200 pyramidal neurons and ~1400 monosynaptic connections using advanced multineuron patch-clamp recordings in slices from human temporal cortex. To disentangle within and between individual sources of heterogeneity, we recorded up to 100 neurons per single subject. We found that neuronal, but not synaptic physiology varied with laminar depth. Connection probability was ~15% throughout layer 2-3. Synaptic amplitudes exhibited heavy-tailed distributions with an inverse power law relationship to short term plasticity. Neurons could be classified into four functional subtypes. These general principles of microcircuit physiology were common across individuals. Our study advances the understanding of human neuron and synaptic diversity from an individual and phenotypic perspective.
Posterior integration and thalamo-frontotemporal broadcasting are impaired in disorders of consciousness
Authors: Panda Rajanikant , López-González Ane , Gilson Matthieu , Gosseries Olivia , Thibaut Aurore , Frasso Gianluca , Cecconi Benedetta , Escrichs Anira , Deco Gustavo , Laureys Steven , Zamora-López Gorka , Annen Jitka 
Published: November 2021

AbstractThe study of the brain’s static and dynamical activity is opening a valuable source of assistance for the clinical assessment of patients with disorders of consciousness. For example, glucose uptake and dysfunctional spread of naturalistic and synthetic stimuli has proven useful to characterize hampered consciousness. However, understanding of the mechanisms behind loss of consciousness following brain injury is still missing. Here, we study the propagation of endogenous and in-silico exogenous perturbations in patients with disorders of consciousness, based upon directed and causal interactions estimated from resting-state fMRI. We found that patients with disorders of consciousness suffer decreased capacity for neural propagation and responsiveness to events, and that this can be related to glucose metabolism as measured with [18F]FDG-PET. In particular, we show that loss of consciousness is related to the malfunctioning of two neural circuits: the posterior cortical regions failing to convey information, in conjunction with reduced broadcasting of information from subcortical, temporal, parietal and frontal regions. These results seed light on the mechanisms behind disorders of consciousness, triangulating network function with basic measures of brain integrity and behavior.HighlightsPropagation of neural events and network responses are disrupted in patients with DoC.Loss of consciousness is related to the malfunctioning of two neural circuits.Posterior cortical regions lack to integrate information in altered consciousness.Breakdown of information broadcasting of subcortical cortical areas in DoC.Loss of network responses in DoC patients is related to glucose metabolism.
Screening and selection of 21 novel microhaplotype markers for ancestry inference in ten Chinese Subpopulations
Authors: Zou Xing , He Guanglin , Liu Jing , Jiang Lirong , Wang Mengge , Chen Pengyu , Hou Yiping , Wang Zheng 
Published: November 2021

AbstractGenetic findings suggested that ethnolinguistically diverse populations in China harbor differentiated genetic structure and complex evolutionary admixture history, which provide the genetic basis and theoretical foundation for forensic biogeographical ancestry inference (BGAI). Forensic assays for BGAI among intracontinental eastern Eurasians were previously conducted mainly based on the SNPs or InDels. Microhaplotypes, as a set of closely linked SNPs within 200 base pairs, possess the advantages of both STR and SNP and have great potential in forensic ancestry inference. However, the developed forensic assay based on the ancestry informative microhaplotypes in the BGAI remained to be comprehensively explored, especially in China with enriching genetic diversity. Here, we described a new BGAI panel based on 21 novel identified ancestry informative microhaplotypes that focused on dissected finer-scale ancestry composition of Chinese populations. We initially screened all possible microhaplotypes with high Fstvalues among five East Asian populations and finally employed 21 candidate microhaplotypes in two multiplex SNaPshot assays. Forensic amplification efficiency and statistically/physically phased haplotypes of the 21 microhaplotypes were validated using both SNaPshot and massively parallel sequencing (MPS) platforms. Followingly, we validated the efficiency of these microhaplotypes for BGAI in 764 individuals from ten Chinese populations. Fine-scale ancestry source and ancestry proportion estimated by the principal component analysis (PCA), multidimensional scaling (MDS), phylogenetic tree and model-based STRUCTURE among worldwide populations and East Asians showed that our customized panel could provide a higher discrimination resolution in both continental population stratification and East Asian regional substructure. East Asian populations could be further classified into linguistically/geographically different intracontinental subpopulations (Tibeto-Burman, Tai-Kadai and others). Finally, we obtained a higher estimated accuracy using training and tested datasets in the microhaplotype-based panel than traditional SNP-based panels. Generally, the above results demonstrated that this microhaplotype panel was robust and suitable for forensic BGAI in Chinese populations, which not only provided a high discriminatory power for continental populations but also discriminated East Asians into linguistically restricted subpopulations.
Prospects of telomere-to-telomere assembly in barley: analysis of sequence gaps in the MorexV3 reference genome
Authors: Navrátilová Pavla , Toegelová Helena , Tulpová Zuzana , Kuo Yi-Tzu , Stein Nils , Doležel Jaroslav , Houben Andreas , Šimková Hana , Mascher Martin 
Published: November 2021

AbstractThe first gapless, telomere-to-telomere (T2T) sequence assemblies of plant chromosomes were reported recently. However, sequence assemblies of most plant genomes remain fragmented. Only recent breakthroughs in accurate long-read sequencing have made it possible to achieve highly contiguous sequence assemblies with a few tens of contigs per chromosome, i.e. a number small enough to allow for a systematic inquiry into the causes of the remaining sequence gaps and the approaches and resources needed to close them. Here, we analyze sequence gaps in the current reference genome sequence of barley cv. Morex (MorexV3). Optical map and sequence raw data, complemented by ChIP-seq data for centromeric histone variant CENH3, were used to estimate the abundance of centromeric, ribosomal DNA and subtelomeric repeats in the barley genome. These estimates were compared with copy numbers in the MorexV3 pseudomolecule sequence. We found that almost all centromeric sequences and 45S ribosomal DNA repeat arrays were absent from the MorexV3 pseudomolecules and that the majority of sequence gaps can be attributed to assembly breakdown in long stretches of satellite repeats. However, missing sequences cannot fully account for the difference between assembly size and flow cytometric genome size estimates. We discuss the prospects of gap closure with ultra-long sequence reads.
Cerebral perfusion imaging: Hypoxia-induced deoxyhemoglobin or gadolinium?
Authors: Sayin E.S , Schulman J. , Poublanc J. , Levine H. , Venkatraghavan L. , Uludag K. , Duffin J. , Fisher J.A. , Mikulis D.J. , Sobczyk O. 
Published: November 2021

AbstractAssessment of resting cerebrovascular perfusion measures (mean transit time, cerebral blood flow and cerebral blood volume) with magnetic resonance imaging currently requires the intravascular injection of the dynamic susceptibility contrast agent gadolinium. An initial comparison between hypoxia-induced deoxyhemoglobin and gadolinium was made for these measures in six healthy participants. A bolus of deoxyhemoglobin is generated in the lung via transient hypoxia induced by an available computer-controlled gas blender technology employing sequential gas delivery (RespirAct™). We hypothesised and confirmed perfusion measures from both susceptibility contrast agents would yield similar spatial patterns of cerebrovascular perfusion measures. We conclude that hypoxia-induced deoxyhemoglobin, an endogenously, non-invasively generated, non-allergenic, non-toxic, recyclable, environmentally innocuous molecule, may be suitable to become the first new magnetic resonance imaging susceptibility contrast agent introduction since gadolinium.
ResPAN: a powerful batch correction model for scRNA-seq data through residual adversarial networks
Authors: Wang Yuge , Liu Tianyu , Zhao Hongyu 
Published: November 2021

AbstractMotivationWith the advancement of technology, we can generate and access large-scale, high dimensional and diverse genomics data, especially through single-cell RNA sequencing (scRNA-seq). However, integrative downstream analysis from multiple scRNA-seq datasets remains challenging due to batch effects.ResultsIn this paper, we propose a light-structured deep learning framework called ResPAN for scRNA-seq data integration. ResPAN is based on Wasserstein Generative Adversarial Network (WGAN) combined with random walk mutual nearest neighbor pairing and fully skip-connected autoencoders to reduce the differences among batches. We also discuss the limitations of existing methods and demonstrate the advantages of our model over seven other methods through extensive benchmarking studies on both simulated data under various scenarios and real datasets across different scales. Our model achieves leading performance on both batch correction and biological information conservation and maintains scalable to datasets with over half a million cells.AvailabilityAn open-source implementation of ResPAN and scripts to reproduce the results can be downloaded from:https://github.com/AprilYuge/ResPAN.Contacthongyu.zhao@yale.edu
A Computational Modeling Framework to Analyze Synovial-Tissue Based Drug Targets and Diagnostic Biomarkers in Rheumatoid Arthritis
Authors: Latawa Paridhi , Chrisman Brianna 
Published: November 2021

AbstractRheumatoid Arthritis (RA) is an inflammatory autoimmune disease that affects 23 million people worldwide. It is a clinically heterogeneous disorder characterized by the attack of inflammatory chemicals on the synovial tissue that lines joints. It is advantageous to develop effective, targeted treatments and identify specific diagnostic biomarkers for RA before extensive joint degradation, bone erosion, and cartilage destruction. Current modes of RA treatments have alleviated and notably halted the progression of RA. Despite this, not many patients reach low disease activity status after treatment, and a significant number of patients fail to respond to medication due to drug non-specificity. While the reasons for these rates remain unknown, the cellular and molecular signatures present in the synovial tissue for RA patients likely play a role in the varied treatment response. Thus, a drug that particularly targets specific genes and networks may have a significant effect in halting the progression of RA. This study evaluates and proposes potential drug targets through in silico mathematical modeling of various pathways of interest in RA. To understand how drugs interact with genes, we built a mathematical model with 30 two-gene and three-gene network interactions and analyzed the effect of 92 different perturbations to rate constants. We determined that inhibition of the LCK-CD4, VAV1-CD4, and MLT-ROR pathways could potentially serve as drug targets. We also found that increased activity of the DEC2-IL1β and the NF-kB-interleukin pathway and the decreased activity of the TNF-α-REV-ERB pathway could serve as diagnostic biomarkers.
hybpiper-rbgv and yang-and-smith-rbgv: Containerization and additional options for assembly and paralog detection in target enrichment data
Authors: Jackson Chris , McLay Todd , Schmidt-Lebuhn Alexander N. 
Published: November 2021

ABSTRACTPREMISEThe HybPiper pipeline has become one of the most widely used tools for the assembly of target enrichment (sequence capture) data for phylogenomic analysis. Between the production of locus sequences and phylogenetic analysis, the identification of paralogs is a critical step ensuring accurate inference of evolutionary relationships. Algorithmic approaches using gene tree topologies for the inference of ortholog groups are computationally efficient and broadly applicable to non-model organisms, especially in the absence of a known species tree. Unfortunately, software compatibility issues, unfamiliarity with relevant programming languages, and the complexity involved in running numerous subsequent analysis steps continue to limit the broad uptake of these approaches and constrain their application in practice.METHODS AND RESULTSWe updated the scripts constituting HybPiper and a pipeline for the inference of ortholog groups (“Yang and Smith”) to provide novel options for the treatment of supercontigs, remove bugs, and seamlessly use the outputs of the former as inputs for the latter. The pipelines were containerised using Singularity and implemented via two Nextflow pipelines for easier deployment and to vastly reduce the number of commands required for their use. We tested the pipelines with several datasets, one of which is presented for demonstration.CONCLUSIONShybpiper-rbgv and yang-and-smith-rbgv provide easy installation, user-friendly experience, and robust results to the phylogenetic community. They are presently used as the analysis pipeline of the Australian Angiosperm Tree of Life project. The pipelines are available at https://github.com/chrisjackson-pellicle.
Chromogranin A plays a crucial role in the age-related development of insulin resistance and hypertension
Authors: Liu Matthew A. , Jati Suborno , Tang Kechun , van den Bogaart Geert , Ghosh Gourisankar , Mahata Sushil K. 
Published: November 2021

ABSTRACTAging is associated with the development of metabolic disorders, including insulin resistance and hypertension. Young mice that are negative for the neuroendocrine prohormone Chromogranin A (CgA knockout, CgA-KO) display two opposite aging phenotypes: hypertension but heightened insulin sensitivity. We determined these phenotypes in aging CgA mice. In comparison, aging wild-type (WT) mice gradually lost glucose tolerance and insulin sensitivity. Moreover, while aging WT mice had increased inflammation with higher plasma TNF-α, IFN-γ and CCL2 and increased mitochondrial fission, these phenotypes were the opposite in aging CgA-KO mice. CgA-KO mice also showed increased expression of mitochondrial and nuclear-encoded complex I genes, implying that they were healthier than WT mice. Most intriguingly, the hypertension in CgA-KO mice was spontaneously reversed with aging. Supplementation of CgA-KO mice with pancreastatin, a hyperglycemic peptide produced from CgA by proteolysis, increased both blood glucose levels and blood pressure, implicating hyperglycemia, and hypertension. We conclude that age-related insulin resistance and hypertension are caused by CgA.
A virtual host model of Mycobacterium tuberculosis infection identifies early immune events as predictive of infection outcomes
Authors: Joslyn Louis R. , Linderman Jennifer J. , Kirschner Denise E. 
Published: November 2021

AbstractTuberculosis (TB), caused by infection with Mycobacterium tuberculosis (Mtb), is one of the world’s deadliest infectious diseases and remains a significant global health burden. TB disease and pathology can present clinically across a spectrum of outcomes, ranging from total sterilization of infection to active disease. Much remains unknown about the biology that drives an individual towards various clinical outcomes as it is challenging to experimentally address specific mechanisms driving clinical outcomes. Furthermore, it is unknown whether numbers of immune cells in the blood accurately reflect ongoing events during infection within human lungs. Herein, we utilize a systems biology approach by developing a whole-host model of the immune response to Mtb across multiple physiologic and time scales. This model, called HostSim, tracks events at the cellular, granuloma, organ, and host scale and represents the first whole-host, multi-scale model of the immune response following Mtb infection. We show that this model can capture various aspects of human and non-human primate TB disease and predict that biomarkers in the blood may only faithfully represent events in the lung at early time points after infection. We posit that HostSim, as a first step toward personalized digital twins in TB research, offers a powerful computational tool that can be used in concert with experimental approaches to understand and predict events about various aspects of TB disease and therapeutics.