bluuebunny/crossref_metadata_2025 huggingface dataset:
GdClean: removal of Gadolinium contamination in mass cytometry data
Authors: Liu Junwei , Liu Lulu , Qu Saisi , Zhang Tongtong , Wang Danyang , Ji Qinghua , Wang Tian , Shi Hongyu , Song Kaichen , Fang Weijia , Chen Wei , Yin Weiwei
Published: July 2021

Motivation

Mass cytometry (Cytometry by Time-Of-Flight, CyTOF) is a single-cell technology that is able to quantify multiplex biomarker expressions and is commonly used in basic life science and translational research. However, the widely used Gadolinium (Gd)-based contrast agents (GBCAs) in magnetic resonance imaging (MRI) scanning in clinical practice can lead to signal contamination on the Gd channels in the CyTOF analysis. This Gd contamination greatly affects the characterization of the real signal from Gd-isotope-conjugated antibodies, severely impairing the CyTOF data quality and ruining downstream single-cell data interpretation.

Results

We first in-depth characterized the signals of Gd isotopes from a control sample that was not stained with Gd-labeled antibodies but was contaminated by Gd isotopes from GBCAs, and revealed the collinear intensity relationship across Gd contamination signals. We also found that the intensity ratios of detected Gd contamination signals to the reference Gd signal were highly correlated with the natural abundance ratios of corresponding Gd isotopes. We then developed a computational method named by GdClean to remove the Gd contamination signal at the single-cell level in the CyTOF data. We further demonstrated that the GdClean effectively cleaned up the Gd contamination signal while preserving the real Gd-labeled antibodies signal in Gd channels. All of these shed lights on the promising applications of the GdClean method in preprocessing CyTOF datasets for revealing the true single-cell information.

Availability and implementation

The R package GdClean is available on GitHub at https://github.com/JunweiLiu0208/GdClean.

Supplementary information

Supplementary data are available at Bioinformatics online.
PhosIDN: an integrated deep neural network for improving protein phosphorylation site prediction by combining sequence and protein–protein interaction information
Authors: Yang Hangyuan , Wang Minghui , Liu Xia , Zhao Xing-Ming , Li Ao
Published: July 2021

Motivation

Phosphorylation is one of the most studied post-translational modifications, which plays a pivotal role in various cellular processes. Recently, deep learning methods have achieved great success in prediction of phosphorylation sites, but most of them are based on convolutional neural network that may not capture enough information about long-range dependencies between residues in a protein sequence. In addition, existing deep learning methods only make use of sequence information for predicting phosphorylation sites, and it is highly desirable to develop a deep learning architecture that can combine heterogeneous sequence and protein–protein interaction (PPI) information for more accurate phosphorylation site prediction.

Results

We present a novel integrated deep neural network named PhosIDN, for phosphorylation site prediction by extracting and combining sequence and PPI information. In PhosIDN, a sequence feature encoding sub-network is proposed to capture not only local patterns but also long-range dependencies from protein sequences. Meanwhile, useful PPI features are also extracted in PhosIDN by a PPI feature encoding sub-network adopting a multi-layer deep neural network. Moreover, to effectively combine sequence and PPI information, a heterogeneous feature combination sub-network is introduced to fully exploit the complex associations between sequence and PPI features, and their combined features are used for final prediction. Comprehensive experiment results demonstrate that the proposed PhosIDN significantly improves the prediction performance of phosphorylation sites and compares favorably with existing general and kinase-specific phosphorylation site prediction methods.

Availability and implementation

PhosIDN is freely available at https://github.com/ustchangyuanyang/PhosIDN.

Supplementary information

Supplementary data are available at Bioinformatics online.
The topology of data: opportunities for cancer research
Authors: Loughrey Ciara F , Fitzpatrick Padraig , Orr Nick , Jurek-Loughrey Anna
Published: July 2021

Motivation

Topological methods have recently emerged as a reliable and interpretable framework for extracting information from high-dimensional data, leading to the creation of a branch of applied mathematics called Topological Data Analysis (TDA). Since then, TDA has been progressively adopted in biomedical research. Biological data collection can result in enormous datasets, comprising thousands of features and spanning diverse datatypes. This presents a barrier to initial data analysis as the fundamental structure of the dataset becomes hidden, obstructing the discovery of important features and patterns. TDA provides a solution to obtain the underlying shape of datasets over continuous resolutions, corresponding to key topological features independent of noise. TDA has the potential to support future developments in healthcare as biomedical datasets rise in complexity and dimensionality. Previous applications extend across the fields of neuroscience, oncology, immunology and medical image analysis. TDA has been used to reveal hidden subgroups of cancer patients, construct organizational maps of brain activity and classify abnormal patterns in medical images. The utility of TDA is broad and to understand where current achievements lie, we have evaluated the present state of TDA in cancer data analysis.

Results

This article aims to provide an overview of TDA in Cancer Research. A brief introduction to the main concepts of TDA is provided to ensure that the article is accessible to readers who are not familiar with this field. Following this, a focussed literature review on the field is presented, discussing how TDA has been applied across heterogeneous datatypes for cancer research.
Accurate large-scale phylogeny-aware alignment using BAli-Phy
Authors: Gupta Maya , Zaharias Paul , Warnow Tandy
Published: July 2021

Motivation

BAli-Phy, a popular Bayesian method that co-estimates multiple sequence alignments and phylogenetic trees, is a rigorous statistical method, but due to its computational requirements, it has generally been limited to relatively small datasets (at most about 100 sequences). Here, we repurpose BAli-Phy as a ‘phylogeny-aware’ alignment method: we estimate the phylogeny from the input of unaligned sequences, and then use that as a fixed tree within BAli-Phy.

Results

We show that this approach achieves high accuracy, greatly superior to Prank, the current most popular phylogeny-aware alignment method, and is even more accurate than MAFFT, one of the top performing alignment methods in common use. Furthermore, this approach can be used to align very large datasets (up to 1000 sequences in this study).

Availability and implementation

See https://doi.org/10.13012/B2IDB-7863273_V1 for datasets used in this study.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cortical Morphology and White Matter Tractography of Three Phylogenetically Distant Primates: Evidence for a Simian Elaboration
Authors: Roumazeilles Lea , Lange Frederik J , Benn R Austin , Andersson Jesper L R , Bertelsen Mads F , Manger Paul R , Flach Edmund , Khrapitchev Alexandre A , Bryant Katherine L , Sallet Jérôme , Mars Rogier B
Published: July 2021

Comparative neuroimaging has been used to identify changes in white matter architecture across primate species phylogenetically close to humans, but few have compared the phylogenetically distant species. Here, we acquired postmortem diffusion imaging data from ring-tailed lemurs (Lemur catta), black-capped squirrel monkeys (Saimiri boliviensis), and rhesus macaques (Macaca mulatta). We were able to establish templates and surfaces allowing us to investigate sulcal, cortical, and white matter anatomy. The results demonstrate an expansion of the frontal projections of the superior longitudinal fasciculus complex in squirrel monkeys and rhesus macaques compared to ring-tailed lemurs, which correlates with sulcal anatomy and the lemur’s smaller prefrontal granular cortex. The connectivity of the ventral pathway in the parietal region is also comparatively reduced in ring-tailed lemurs, with the posterior projections of the inferior longitudinal fasciculus not extending toward parietal cortical areas as in the other species. In the squirrel monkeys we note a very specific occipito-parietal anatomy that is apparent in their surface anatomy and the expansion of the posterior projections of the optical radiation. Our study supports the hypothesis that the connectivity of the prefrontal-parietal regions became relatively elaborated in the simian lineage after divergence from the prosimian lineage.
Reconstructing baselines: use of habitat suitability modelling to predict pre-fishing condition of a Vulnerable Marine Ecosystem
Authors: Downie Anna-Leena , Piechaud Nils , Howell Kerry , Barrio Froján Christopher , Sacau Mar , Kenny Andrew
Published: July 2021

As industrialized fishing activities have moved into deeper water, the recognition of Vulnerable Marine Ecosystems (VMEs) has become important for the protection of the deep-sea. Our limited knowledge on the past and present distribution of VMEs hinders our ability to manage bottom fisheries effectively. This study investigated whether accounting for bottom fishing intensity (derived from Vessel Monitoring System records) as a predictor in habitat suitability models can (1) improve predictions of, and (2) provide estimates for a pre-fishing baseline for the distribution and biomass of a VME indicator taxon. Random Forest models were applied to presence/absence and biomass of Geodia sponges and environmental variables with and without bottom fishing intensity. The models including fishing were further used to predict distribution and biomass of Geodia to a pre-fishing scenario. Inclusion of fishing pressure as a predictive term significantly improved model performance for both sponge presence and biomass. This study has demonstrated a way to produce a more accurate picture of the current distribution of VMEs in the study area. The pre-fishing scenario predictions also identified areas of suitable Geodia habitat that are currently impacted by fishing, suggesting that sponge habitat and biomass have been impacted by bottom trawling activities.
Controllability of second-order differential equations with state-dependent delay
Authors: Karthikeyan K , Tamizharasan D , Nieto J J , Nisar Kottakkaran Sooppy
Published: July 2021

The intention of this article is to analyse the existence of controllability of differential equations of second order with state-dependent delay by using the cosine function theory. Also, well-posedness of the solution to the problem is examined. In the end, examples are provided to represent the theory.
On Endomorphisms of Algebraic Varieties
Authors: Das Nilkantha
Published: July 2021

Consider an endomorphism of an algebraic variety over an algebraically closed field of characteristic zero that is injective on the complement of a proper closed subvariety. We prove that such an endomorphism is an automorphism, provided the morphism is quasi-finite. We also show that if the codimension of the subvariety is at least $2$, the endomorphism is an automorphism, provided the morphism is affine, or the variety is affine, or the variety has a normalization, which is locally factorial.
Post-transcriptional regulation of immunological responses by Regnase-1-related RNases
Authors: Uehata Takuya , Takeuchi Osamu
Published: July 2021

Regulation of messenger RNA (mRNA) decay plays a crucial role in the control of gene expression. Canonical mRNA decay pathways are initiated by deadenylation and decapping and are followed by exonucleolytic degradation. However, recent studies revealed that endoribonucleolytic cleavage also mediates mRNA decay, and both exoribonucleolytic and endoribonucleolytic decay pathways are important for the regulation of immune responses. Regnase-1 functions as an endoribonuclease to control immunity by damping mRNAs. Particularly, Regnase-1 controls cytokines and other inflammatory mediators by recognizing their mRNAs via stem–loop structures present in the 3′ untranslated regions. Regnase-1 was found to be critical for human inflammatory diseases such as ulcerative colitis and idiopathic pulmonary fibrosis. Furthermore, a set of Regnase-1-related RNases contribute to immune regulation as well as antiviral host defense. In this review, we provide an overview of recent findings as to immune-related RNA-binding proteins (RBPs) with an emphasis on stem–loop-mediated mRNA decay via Regnase-1 and related RNases and discuss how the function of these RBPs is regulated and contributes to inflammatory disorders.
Clinic, community, and in-between: the influence of space on real-time translation of medical expertise by frontline healthcare professionals in marginal tribal communities
Authors: Tripathi Vinayak R , Jha Harsh Kumar , Popli Manish , Shah Pankaj , Desai Gayatri
Published: July 2021

In this article, we explore real-time translation work undertaken by frontline healthcare professionals as they interact with marginal tribal communities in Western India. Our 1-year ethnographic study of a healthcare organization delivering obstetric and gynaecological care to tribal communities helps us understand how obstetric counsellors translate allopathic medical expertise across epistemological boundaries to the tribal community they serve, in localized comprehensible forms. We identify four distinct mechanisms of translation work—Interpreting, Annotating, Norming, and Justifying—which differentially deploy and integrate elements of tribal vocabulary, symbols, knowledge, and imaginations of health and body with specific aspects of clinical diagnosis and prescription, making the latter meaningful and actionable in the process. Furthermore, we use configurational approach—Qualitative Comparative Analysis—to investigate how the type of space where the interaction between the counsellors and tribal women patients happens influences the translation work undertaken. We find that counsellors engage in spatially differentiated translation work. They predominantly use justifying and norming in clinical space (hospital); interpreting and annotating in community space (village or school); and interpreting and norming in the overlapping in-between space (outdoor patient department). Our study contributes to translation literature by showing how real-time translation is undertaken in practice, especially in a setting representing high-stakes institutional translation, and how translation work is influenced by the type of space in which interactions happen.
Right-sided Bochdalek hernia in an adult: a case report
Authors: Pun Ashis , Dhoubhadel Pratibha , Dawadi Kamal
Published: July 2021

Bochdalek hernia (BH) is the most common type of congenital diaphragmatic hernia and is usually left-sided. It typically presents in neonates and diagnosis in adults is a rarity. To date only 34 reported cases of right-sided BH have been surgically managed in adults in literature. We review a 21-year-old female with a right-sided BH diagnosed as acute calculus cholecystitis and underwent laparoscopic cholecystectomy. The diagnosis of BH was made incidentally during surgery. The hernia did not have a sac with no hernial contents. It was treated via laparoscopic intracorporeal suturing and patient postoperative period was uneventful. Right-sided BH is rare. Regardless of the symptoms surgical treatment should be done to avoid risk of visceral strangulation.
A phosphate binding pocket is a key determinant of exo- versus endo-nucleolytic activity in the SNM1 nuclease family
Authors: Baddock Hannah T , Newman Joseph A , Yosaatmadja Yuliana , Bielinski Marcin , Schofield Christopher J , Gileadi Opher , McHugh Peter J
Published: July 2021

The SNM1 nucleases which help maintain genome integrity are members of the metallo-β-lactamase (MBL) structural superfamily. Their conserved MBL-β-CASP-fold SNM1 core provides a molecular scaffold forming an active site which coordinates the metal ions required for catalysis. The features that determine SNM1 endo- versus exonuclease activity, and which control substrate selectivity and binding are poorly understood. We describe a structure of SNM1B/Apollo with two nucleotides bound to its active site, resembling the product state of its exonuclease reaction. The structure enables definition of key SNM1B residues that form contacts with DNA and identifies a 5′ phosphate binding pocket, which we demonstrate is important in catalysis and which has a key role in determining endo- versus exonucleolytic activity across the SNM1 family. We probed the capacity of SNM1B to digest past sites of common endogenous DNA lesions and find that base modifications planar to the nucleobase can be accommodated due to the open architecture of the active site, but lesions axial to the plane of the nucleobase are not well tolerated due to constriction around the altered base. We propose that SNM1B/Apollo might employ its activity to help remove common oxidative lesions from telomeres.
Soft and disordered hyperuniform elastic metamaterials for highly efficient vibration concentration
Authors: Tang Hanchuan , Hao Zhuoqun , Liu Ying , Tian Ye , Niu Hao , Zang Jianfeng
Published: July 2021

Vibrations, which widely exist throughout the world, could be a nearly endless and locally obtained green energy source. It has been a long-standing challenge to efficiently utilize dispersed vibration energy, especially within the high-frequency range, since the amplitudes of high-frequency vibrations in local parts of objects are relatively weak. Here, for the first time, we propose a soft and disordered hyperuniform elastic metamaterial (DHEM), achieving a remarkable concentration of vibrations in broad frequency bands by a maximum enhancement factor of ∼4000 at 1930 Hz. The DHEM, with rational sizes from ∼1 cm to ∼1000 cm, covers a broad range of frequencies from ∼10 Hz to ∼10 kHz, which are emitted by many vibration sources including domestic appliances, factories and transportation systems, for example. Moreover, the performance of the soft DHEM under deformation is validated, enabling conformal attachments on uneven objects. Our findings lay the groundwork for reducing traditional energy consumption by recovering some of the energy dissipated by devices in the working world.
Accurate and broadband manipulations of harmonic amplitudes and phases to reach 256 QAM millimeter-wave wireless communications by time-domain digital coding metasurface
Authors: Chen Ming Zheng , Tang Wankai , Dai Jun Yan , Ke Jun Chen , Zhang Lei , Zhang Cheng , Yang Jin , Li Lianlin , Cheng Qiang , Jin Shi , Cui Tie Jun
Published: July 2021

We propose a theoretical mechanism and new coding strategy to realize extremely accurate manipulations of nonlinear electromagnetic harmonics in ultrawide frequency band based on a time-domain digital coding metasurface (TDCM). Using the proposed mechanism and coding strategy, we design and fabricate a millimeter-wave (mmWave) TDCM, which is composed of reprogrammable meta-atoms embedded with positive-intrinsic-negative diodes. By controlling the duty ratios and time delays of the digital coding sequences loaded on a TDCM, experimental results show that both amplitudes and phases of different harmonics can be engineered at will simultaneously and precisely in broad frequency band from 22 to 33 GHz, even when the coding states are imperfect, which is in good agreement with theoretical calculations. Based on the fabricated high-performance TDCM, we further propose and experimentally realize a large-capacity mmWave wireless communication system, where 256 quadrature amplitude modulation, along with other schemes, is demonstrated. The new wireless communication system has a much simpler architecture than the currently used mmWave wireless systems, and hence can significantly reduce the hardware cost. We believe that the proposed method and system architecture can find vast application in future mmWave and terahertz-wave wireless communication and radar systems.
English Overseas Empire
Authors: Roper L. H.
Published: July 2021

The English (after the Union of England, Scotland, and Wales in 1707, the British) Overseas Empire famously encompassed the globe. The range of scholarship related to this phenomenon stretches accordingly. This article focuses on contributions that consider the period prior to c. 1700 but provides links to other Oxford Bibliographies articles that include entries on non-English perspectives on the expansion of English overseas interests more fully, entries on the cultural interactions generated by that expansion, entries that relate to the later period, and entries that provide additional references to the topics discussed here. The emergence of an English Overseas Empire might be regarded as one of the most significant yet one of the more unlikely consequences of the Reformation and the Renaissance. In the fifteenth century, England suffered civil war and had its overseas territory reduced to Calais and the Pale of Dublin while its foreign mercantile sphere concentrated on the Baltic region, Antwerp, and Seville. The English break with Rome severed longstanding Anglo-Iberian economic ties and provided the religious-ideological frame for trading, plundering, and colonizing forays against the “popish” Iberians the success of whose initiatives had left the English scandalously behind in the minds of early imperial cheerleaders. By the 1640s, English “private” initiatives had established presences in Africa, America, and Asia, although the scale of these operations eventually proved beyond the capacity of these projectors, thus necessitating governmental intervention. After 1689, France replaced Spain as the imperial bogey, but an anti-Catholic imperial ideology, which employed a language of liberty and virtue derived from humanism, intensified as English political and economic ambitions expanded and direct government involvement in empire increased. Both this expansion and the cultural interactions it generated tracked changing English cultural and political sensibilities: contemporary authors and artists acclaimed English overseas endeavor as a hallmark of civilization, modernity, capitalism, and progress; the stridency of this celebratory view accompanied a seemingly inexorable coloring of the globe pink prior to World War II. English overseas expansion also entailed deep involvement in the enslavement of Africans—in terms of both exporting enslaved persons from sub-Saharan Africa throughout the Western Hemisphere and importing these people to labor on English plantations—a reality that has begun to receive significant attention only recently. It also involved the often-nasty subjugation of societies in situ, another reality that has also received a recent intensive rethink in the postcolonial era that began in the 1960s. The careful treatment of the responses of those societies to British incursions has become another recent and welcome development.
Death From Primary Amebic Meningoencephalitis After Recreational Water Exposure During Recent Travel to India—Santa Clara County, California, 2020
Authors: Harris Glenn R , Karmarkar Ellora N , Quenelle Rebecca , Chaille Lyndsey , Madhok Jai , Tien Vivian , Gupta Jyoti , Jain Seema , Liu Maria , Roy Shantanu , Narasimhan Supriya , Kimura Akiko , Cope Jennifer R , Ali Ibne Karim M
Published: July 2021

Background

In February 2020, a man returned to the United States after an 11-day trip to India and died of primary amebic meningoencephalitis (PAM), caused by nasal exposure to the free-living ameba Naegleria fowleri found in warm water. We identified potential exposures, confirmed etiology, and described the molecular epidemiology of the infection.

Methods

We reviewed medical records to describe his clinical course and interviewed his family to determine water exposures. Genotyping was performed on the N. fowleri strain and compared with North American strains through repetitive nonpolymorphic nuclear loci analysis to identify differences. We reviewed N. fowleri strains in the National Center for Biotechnology Information database (GenBank) to determine genotypes present in India.

Results

The patient became acutely encephalopathic 3 days after returning; the only known nasal water exposure was at an indoor swimming pool in India 5 days earlier. Cerebrospinal fluid (CSF) testing demonstrated neutrophil-predominant pleocytosis and low glucose, but negative gram stain and culture. CSF microscopy revealed trophozoites; N. fowleri was detected by real-time polymerase chain reaction. Classical genotyping confirmed genotype I, common in the United States and among Indian strains in GenBank. The North American N. fowleri strains and the patient’s strain varied at 5 nonpolymorphic loci.

Conclusions

A man died from PAM after likely exposure at a vacation rental pool in India. We recommend including PAM in the differential diagnosis when CSF studies suggest bacterial meningitis but gram stain is negative. Genotyping can advance our understanding of N. fowleri molecular epidemiology and support future investigations.
Integrase Inhibitor Prescribing Disparities in the DC and Johns Hopkins HIV Cohorts
Authors: Monroe Anne K , Levy Matthew E , Greenberg Alan E , Keruly Jeanne C , Moore Richard D , Horberg Michael A , Kulie Paige , Mohanraj Bernadine S , Kumar Princy N , Castel Amanda D ,   DC Cohort Executive Committee, D’Angelo Lawrence , Rakhmanina Natella , Kharfen Michael , Serlin Michael , Kumar Princy , Bamdad Aria , Bezabeh Tsedenia , Reamer Susan , Sapozhnikova Alla , Temprosa Marinella , Younes Naji , Liu Jinxi , Xiao Kevin , Byrne Morgan , Castel Amanda , Greenberg Alan , Jaurretche Maria , Levy Matthew , Monroe Anne , Peterson James , Happ Lindsey Powers , Wilbourn Brittany , Ma Yan , Akselrod Hana , Wilcox Ronald , Rana Sohail , Horberg Michael , Fernandez Ricardo , Hebou Annick , Dieffenbach Carl , Masur Henry , Bordon Jose , Teferi Gebeyehu , Benator Debra , Ruiz Maria Elena , Abbott Stephen
Published: July 2021

Integrase inhibitors (INSTIs) are recommended by expert panels as initial therapy for people with HIV. Because there can be disparities in prescribing and uptake of novel and/or recommended therapies, this analysis assessed potential INSTI prescribing disparities using a combined data set from the Johns Hopkins HIV Clinical Cohort and the DC Cohort. We performed multivariable logistic regression to identify factors associated with ever being prescribed an INSTI. Disparities were noted, including clinic location, age, and being transgender. Identifying disparities may allow clinicians to focus their attention on these individuals and ensure that therapy decisions are grounded in valid clinical reasons.
Acute Hepatitis A Viral Infection in People With HIV With Previously Documented Hepatitis A Immunity or Appropriate Vaccination: A Case Series
Authors: McLaughlin Stephanie E , Simmons Jason D , Armstrong Hilary , Gonzales Elysia , Rakita Robert M , Duchin Jeffrey S , Patel Rena C
Published: July 2021

We describe 4 people with HIV (PWH) who acquired acute hepatitis A (HAV) infection during recent King County, Washington, outbreaks despite documented immunity and/or vaccination. HAV revaccination may be needed in PWH with risk factors for HAV infection regardless of preexisting immunity.
SARS-CoV-2 Cumulative Incidence and Period Seroprevalence: Results From a Statewide Population-Based Serosurvey in California
Authors: Lamba Katherine , Bradley Heather , Shioda Kayoko , Sullivan Patrick S , Luisi Nicole , Hall Eric W , Mehrotra Megha L , Lim Esther , Jain Seema , Kamali Amanda , Sanchez Travis , Lopman Benjamin A , Fahimi Mansour , Siegler Aaron J
Published: July 2021

Background

California has reported the largest number of coronavirus disease 2019 (COVID-19) cases of any US state, with more than 3.5 million confirmed as of March 2021. However, the full breadth of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in California is unknown as reported cases only represent a fraction of all infections.

Methods

We conducted a population-based serosurvey, utilizing mailed, home-based SARS-CoV-2 antibody testing along with a demographic and behavioral survey. We weighted data from a random sample to represent the adult California population and estimated period seroprevalence overall and by participant characteristics. Seroprevalence estimates were adjusted for waning antibodies to produce statewide estimates of cumulative incidence, the infection fatality ratio (IFR), and the reported fraction.

Results

California’s SARS-CoV-2 weighted seroprevalence during August–December 2020 was 4.6% (95% CI, 2.8%–7.4%). Estimated cumulative incidence as of November 2, 2020, was 8.7% (95% CrI, 6.4%–11.5%), indicating that 2 660 441 adults (95% CrI, 1 959 218–3 532 380) had been infected. The estimated IFR was 0.8% (95% CrI, 0.6%–1.0%), and the estimated percentage of infections reported to the California Department of Public Health was 31%. Disparately high risk for infection was observed among persons of Hispanic/Latinx ethnicity and people with no health insurance and who reported working outside the home.

Conclusions

We present the first statewide SARS-CoV-2 cumulative incidence estimate among adults in California. As of November 2020, ~1 in 3 SARS-CoV-2 infections in California adults had been identified by public health surveillance. When accounting for unreported SARS-CoV-2 infections, disparities by race/ethnicity seen in case-based surveillance persist.
The extreme space weather events in October 1788
Authors: Hattori Kentaro , Hayakawa Hisashi , Ebihara Yusuke
Published: July 2021

Solar eruptions launch interplanetary coronal mass ejections (ICMEs) and cause geomagnetic storms and equatorial extension of the auroral oval. Their rare and unique nature has made analyses of historical events extremely important to increase their data availability. In this study, we analyzed the space weather event of 1788 October, which was characterized with simultaneous auroral observations. We extended archival surveys and confirmed the auroral visibilities down to Barcelona (46.0° MLAT) on October 21/22 as well as Mizuhara (27.5° MLAT) and Rome (44.8° MLAT) on October 22/23. The end of auroral reports overlapped with a reported declination disturbance at Mannheim, indicating a ΔD amplitude of ≥1.15°. Two positive excursions of ΔD were recorded, lasting for several tens of minutes. Upward field-aligned currents could have flowed poleward of Mannheim associated with substorms. We identified the equatorial boundary of the auroral oval down to 46.5° ILAT in the European sector and approximately ≤41.6° ILAT in the Japanese sector. This is compared with the reported equatorial auroral boundaries during extreme storms. The long storm sequence indicates the arrival of multiple ICMEs, thereby enhancing solar activity at that time. This sequence is indeed contextualized immediately after the maximum of Solar Cycle 4. Because sunspot observations are extremely scarce around 1788, it is challenging to identify the source active region. This in turn makes these auroral records valuable for the analyses of long-term solar activity before the onset of the Dalton Minimum.
Potential metabolic mechanisms for inhibited chloroplast nitrogen assimilation under high CO2
Authors: Zhao Hong-Long , Chang Tian-Gen , Xiao Yi , Zhu Xin-Guang
Published: July 2021

Improving photosynthesis is considered a major and feasible option to dramatically increase crop yield potential. Increased atmospheric CO2 concentration often stimulates both photosynthesis and crop yield, but decreases protein content in the main C3 cereal crops. This decreased protein content in crops constrains the benefits of elevated CO2 on crop yield and affects their nutritional value for humans. To support studies of photosynthetic nitrogen assimilation and its complex interaction with photosynthetic carbon metabolism for crop improvement, we developed a dynamic systems model of plant primary metabolism, which includes the Calvin–Benson cycle, the photorespiration pathway, starch synthesis, glycolysis–gluconeogenesis, the tricarboxylic acid cycle, and chloroplastic nitrogen assimilation. This model successfully captures responses of net photosynthetic CO2 uptake rate (A), respiration rate, and nitrogen assimilation rate to different irradiance and CO2 levels. We then used this model to predict inhibition of nitrogen assimilation under elevated CO2. The potential mechanisms underlying inhibited nitrogen assimilation under elevated CO2 were further explored with this model. Simulations suggest that enhancing the supply of α-ketoglutarate is a potential strategy to maintain high rates of nitrogen assimilation under elevated CO2. This model can be used as a heuristic tool to support research on interactions between photosynthesis, respiration, and nitrogen assimilation. It also provides a basic framework to support the design and engineering of C3 plant primary metabolism for enhanced photosynthetic efficiency and nitrogen assimilation in the coming high-CO2 world.
Gradient flow exact renormalization group: Inclusion of fermion fields
Authors: Miyakawa Yuki , Suzuki Hiroshi
Published: July 2021

The gradient flow exact renormalization group (GFERG) is an exact renormalization group motivated by the Yang--Mills gradient flow and its salient feature is a manifest gauge invariance. We generalize this GFERG, originally formulated for the pure Yang--Mills theory, to vector-like gauge theories containing fermion fields, keeping the manifest gauge invariance. For the chiral symmetry we have two options: one possible formulation preserves the conventional form of the chiral symmetry and the other simpler formulation realizes the chiral symmetry in a modified form à la Ginsparg--Wilson. We work out a gauge-invariant local Wilson action in quantum electrodynamics to the lowest nontrivial order of perturbation theory. This Wilson action reproduces the correct axial anomaly in $D=2$.
Phase 3 Trials of Enhanced Versus Usual Care Physical Therapy for Patients at Risk of Poor Outcome Following Knee Arthroplasty: A Perspective on Meaning and a Way Forward
Authors: Riddle Daniel L , Hamilton David F , Dumenci Levent , Beard David J
Published: July 2021

Physical therapy is routinely delivered to patients after discharge from the hospital following knee arthroplasty. Posthospitalization physical therapy is thought to be beneficial, particularly for those patients most at risk of poor outcome, the subgroup with persistent function-limiting pain, despite an apparently successful surgery. Research teams have undertaken 3 large-scale multicenter Phase 3 randomized clinical trials designed specifically for patients at risk of poor outcome following knee arthroplasty. All 3 trials screened for poor outcome risk using different methods and investigated different physical therapist interventions delivered in different ways. Despite the variety of types of physical therapy and mode of delivery, all trials found no effects of the enhanced treatment compared with usual care. In all cases, usual care required a lower dosage of physical therapy compared with the enhanced interventions. This Perspective compares and contrasts the 3 trials, speculates on factors that could explain the no-effect findings, and proposes areas for future study designed to benefit the poor outcome phenotype.
Poor Recovery of Activities-of-Daily-Living Function Is Associated With Higher Rates of Postsurgical Hospitalization After Total Joint Arthroplasty
Authors: Falvey Jason , Bade Michael J , Forster Jeri E , Stevens-Lapsley Jennifer E
Published: July 2021

Objective

Medicare beneficiaries are increasingly using home health (HH) as the first postacute care setting after hospital discharge following total joint arthroplasty (TJA). Yet, prior research has shown that changes in payment models for TJA may negatively influence functional outcomes for Medicare beneficiaries. The purpose of this study was to evaluate the impact of poor functional outcomes during an HH episode of care on hospitalization risk for older recipients of TJA.

Methods

For this study, 5822 Medicare beneficiaries who underwent elective TJA and subsequently participated in HH care following hospital discharge were identified using Medicare hospitalizations records and HH claims. Recovery of activities-of-daily-living (ADL) function was evaluated using patient assessment data completed at HH admission and discharge from the Medicare Outcomes and Assessment Information Set (OASIS). Hospitalization outcomes were captured from Medicare hospital claims. Cox proportional hazards regression was used to evaluate the hazard ratio for hospitalization after HH discharge.

Results

The 5822 Medicare beneficiaries who received a TJA and subsequently were discharged to HH were evaluated (n = 3989 [68.6%] following total knee replacement, n = 1883 [31.4%]) following total hip replacement). Nearly 9% (n = 534) of patients did not improve their ability to perform ADLs during the HH episode; this lack of improvement was associated with a more than 2-fold increase in hospital readmission rate following HH discharge (2.3% vs 4.9%). In adjusted models, there was a significant 77% increase (hazard ratio = 1.77; 95% CI = 1.14–2.74) in hospitalization risk during the 90-day postsurgical period.

Conclusion

Poor recovery of ADL function in HH settings following TJA is strongly associated with elevated risk of future hospitalizations.

Impact

Medicare beneficiaries who fail to make substantive improvements in basic ADL function during HH care episodes following TJA may need intensive monitoring from interdisciplinary team members across the continuum of care, especially during transitions from home care to outpatient care.

Lay Summary

An increasing number of patients receive home health care after joint replacement surgery, but outcomes after home health are unclear. These findings suggest that improvements in basic tasks such as walking or bathing are associated with a lower likelihood of hospitalization.
How do clinical and socioeconomic factors impact on work disability in early axial spondyloarthritis? Five-year data from the DESIR cohort
Authors: Nikiphorou Elena , Boonen Annelies , Fautrel Bruno , Richette Pascal , Landewé Robert , van der Heijde Désirée , Ramiro Sofia
Published: July 2021

Objectives

To investigate the impact of clinical and socioeconomic factors on work disability (WD) in early axial spondyloarthritis (axSpA).

Methods

Patients from the DESIR cohort with a clinical diagnosis of axSpA were studied over 5 years. Time to WD and potential baseline and time-varying predictors were explored, with a focus on socioeconomic (including ethnicity, education, job-type, marital/parental status) and clinical (including disease activity, function, mobility) factors. Univariable analyses, collinearity and interaction tests guided subsequent multivariable time-varying Cox survival analyses.

Results

From 704 patients eligible for this study, the estimated incidence of WD among those identified as at risk (n = 663, 94%), and across the five years of DESIR, was 0.05 (95% CI 0.03, 0.06) per 1000 person-days. Significant differences in baseline socioeconomic factors, including lower educational status and clinical measures, including worse disease activity, were seen in patients developing WD over follow-up, compared with those who never did. In the main multivariable model, educational status was no longer predictive of WD, whereas the AS disease activity score (ASDAS) and the BASFI were significantly and independently associated with a higher hazard of WD [HR (95%CI) 1.79 (1.27, 2.54) and 1.42 (1.22, 1.65), respectively].

Conclusion

WD was an infrequent event in this early axSpA cohort. Nevertheless, clinical factors were among the strongest predictors of WD, over socioeconomic factors, with worse disease activity and function independently associated with a higher hazard of WD. Disease severity remains a strong predictor of adverse work outcome even in early disease, despite substantial advances in therapeutic strategies in axSpA.
Methomyl-induced nephrotoxicity and protective effect of curcumin in male rats
Authors: Aslanturk Ayse , Kalender Yusuf
Published: July 2021

We investigated the ameliorative effect of the curcumin against methomyl-induced potential nephrotoxicity in Wistar albino male rats. In the present study, curcumin (100 mg kg−1 bw), methomyl (0,8 mg kg−1 bw) and methomyl plus curcumin were given to rats by oral for 28 days (for subacute examination). Concentrations of blood urea nitrogen, uric acid and creatinine in serum and malondialdehyde level and activities of antioxidant enzyme (superoxide dismutase, catalase, glutathione peroxidase and glutathione S transferase) and histopathological alterations in kidney tissues were studied. Methomyl caused an increment in the concentrations of blood urea nitrogen, creatinine, uric acid and MDA levels. In addition, methomyl caused a diminution in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S transferase. Tubular and glomerular degenerations occurred in the kidney tissues of methomyl-received rats. However, coadministration of curcumin with methomyl significantly minimized the adverse effects of methomyl on kidney function parameters, lipid peroxidation and antioxidant enzyme activities and histological structure of kidney tissue. The results showed that curcumin significantly mitigated methomyl-induced nephrotoxicity in rats.
1: Fat Grafting Improves Dorsal Skin Fibrosis after Radiation in an Engrailed-1 Mouse Model
Authors: Abbas Darren B. , Fahy Evan J. , Lavin Christopher , Griffin Michelle , Adem Sandeep , Diaz Deleon Nestor M. , Mascharak Shamik , King Megan , Lee Daniel , Longaker Michael T. , Wan Derrick C.
Published: July 2021

Purpose: Fat grafting is known to rejuvenate and improve fibrosis in irradiated skin, but the underlying mechanisms behind these effects are poorly understood. We have previously identified the Engrailed-1 fibroblast sub-population as having a role in post-natal dorsal skin fibrosis in mice. Using a radiation model to the scalp of Engrailed-1 mice, we sought to better understand the regenerative effects of fat grafting in irradiated tissue.

Methods: Adult (60-day old) En1

Cre

;R26

mTmG
transgenic mice (n=5) underwent total body irradiation with 9 Gy for immunodepletion. Mice were then immediately reconstituted with 2 million nucleated bone marrow cells from donor NSG(NOD.CB17-Prkdcs

scid
/J) mice via retro-orbital injections. Reconstitution was confirmed with fluorescence-activated cell sorting (FACS) 2 weeks after whole body irradiation. Mice scalps were then irradiated with 5 Gy every other day for 12 days (30 Gy total) and allowed to recover for 4 weeks to facilitate fibrotic conversion. Irradiated scalps were grafted with 200μL of fresh human lipoaspirate. Graph retention was measured in-vivo for 8 weeks using Micro-Computed Tomography Scanner (Bruker SkyScan 1726™) and scalp skin was harvest for histology.

Results: Two weeks post bone-marrow transplant, >90% of circulating hematopoietic cells (CD45+) cells in En1

Cre

;R26

mTmG
reporter mice were non-fluorescent, signifying successful reconstitution. Volumetric analysis of fat grafting in-vivo was performed using 3-dimensional reconstruction. At 8 weeks post-grafting, 4 of the 5 grafts demonstrated >50% graft retention, confirming successful grafting. Histological sections of scalp skin 8 weeks post-grafting demonstrated significantly less En1+GFP cells compared to non-grafted scalp skin, signifying less presence of En1

+
fibroblasts. Furthermore, histology demonstrated significantly less dermal thickening, epidermal thinning, and collagen deposition and disorganization in fat grafted irradiated scalp skin compared to non-grafted scalp skin.

Conclusion: Fat grafting mitigates radiation-induced fibrosis in scalp skin by decreasing collagen deposition, remodeling collagen formation, decreasing epidermal thinning, and reducing presence of pro-fibrotic fibroblast sub-populations.
QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease
Authors: Bauer-Rowe Khristian E. , Hyunh Jeong , Foster Deshka S. , Griffin Michelle , Mascharak Shamik , desJardins-Park Heather , Norton Jeffrey A. , Longaker Michael T.
Published: July 2021

Purpose: Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by patchy, transmural inflammation throughout the digestive tract and creeping fat formation. Thirty percent of CD patients develop strictures, eighty percent of which will require surgery. Creeping fat is associated with stricture formation, but its role in intestinal fibrosis remains unclear. Here, we present a novel surgical model of intestinal fibrosis and show by lineage tracing that creeping fat adipocytes convert to fibroblasts that contribute to fibrosis.

Methods: We developed a novel surgical model of IBD that avoids the chronic use of caustic agents by creating a longitudinal, anti-mesenteric colotomy in the mouse transverse colon that is closed transversally. We performed Masson’s trichrome staining to assess collagen deposition. Finally, we performed lineage tracing of mature adipocytes in Adiponectin-Cre; mTmG mice and characterized adipocyte-derived cells by immunostaining.

Results: Our surgical model mimics key features of human strictures, including the formation of creeping fat around the injury site, increased bowel wall thickness, collagen deposition, and transmural adipocyte infiltration by post-operative day (POD) 7. Immunostaining for adipocyte and fibroblast markers confirmed the presence of transmural adipocytes adjacent to fibroblasts. Lineage tracing of mature adipocytes in Adiponectin-Cre; mTmG mice revealed adipocyte-derived cells that infiltrate the wound site that lose expression of adipocyte lineage markers, gain expression of fibroblast markers, produce collagen, and respond to TGF-β signaling.

Conclusions: Our novel surgical colotomy model represents a viable approach to study intestinal fibrosis and creeping fat without the long-term use of caustic agents. Lineage tracing of mature creeping fat adipocytes demonstrates that adipocytes convert to fibroblasts that infiltrate the injury site and participate in fibrotic responses. Taken together, these findings suggest that creeping fat contributes to intestinal fibrosis in part through the local conversion of adipocytes to fibroblasts.