bluuebunny/crossref_metadata_2025 huggingface dataset:
A nuclear redox sensor modulates gene activation andvarswitching inPlasmodium falciparum
Authors: Heinberg Adina , Amit-Avraham Inbar , Mitesser Vera , Simantov Karina , Goyal Manish , Nevo Yuval , Kandelis-Shalev Sofia , Thompson Emilie , Dzikowski Ron
Published: August 2022

The virulence ofPlasmodium falciparum, which causes the deadliest form of human malaria, is attributed to its ability to evade the human immune response. These parasites “choose” to express a single variant from a repertoire of surface antigens called PfEMP1, which are placed on the surface of the infected red cell. Immune evasion is achieved by switches in expression betweenvargenes, each encoding a differentPfEMP1 variant. While the mechanisms that regulate mutually exclusive expression ofvargenes are still elusive, antisense long-noncoding RNAs (lncRNAs) transcribed from the intron of the activevargene were implicated in the “choice” of the single activevargene. Here, we show that this lncRNA colocalizes with the site ofvarmRNA transcription and is anchored to thevarlocus via DNA:RNA interactions. We define thevarlncRNA interactome and identify a redox sensor,P. falciparumthioredoxin peroxidase I (PfTPx-1), as one of the proteins associated with thevarantisense lncRNA. We show thatPfTPx-1 localizes to a nuclear subcompartment associated with active transcription on the nuclear periphery, in ring-stage parasite, whenvartranscription occurs. In addition,PfTPx-1 colocalizes with S-adenosylmethionine synthetase (PfSAMS) in the nucleus, and its overexpression leads to activation ofvar2csa,similar to overexpression ofPfSAMS. Furthermore, we show thatPfTPx-1 knockdown alters thevarswitch rate as well as activation of additional gene subsets. Taken together, our data indicate that nuclearPfTPx-1 plays a role in gene activation possibly by providing a redox-controlled nuclear microenvironment ideal for active transcription.
A spatiotemporal decay model of human mobility when facing large-scale crises
Authors: Li Weiyu , Wang Qi , Liu Yuanyuan , Small Mario L. , Gao Jianxi
Published: August 2022

A common feature of large-scale extreme events, such as pandemics, wildfires, and major storms is that, despite their differences in etiology and duration, they significantly change routine human movement patterns. Such changes, which can be major or minor in size and duration and which differ across contexts, affect both the consequences of the events and the ability of governments to mount effective responses. Based on naturally tracked, anonymized mobility behavior from over 90 million people in the United States, we document these mobility differences in space and over time in six large-scale crises, including wildfires, major tropical storms, winter freeze and pandemics. We introduce a model that effectively captures the high-dimensional heterogeneity in human mobility changes following large-scale extreme events. Across five different metrics and regardless of spatial resolution, the changes in human mobility behavior exhibit a consistent hyperbolic decline, a pattern we characterize as “spatiotemporal decay.” When applied to the case of COVID-19, our model also uncovers significant disparities in mobility changes—individuals from wealthy areas not only reduce their mobility at higher rates at the start of the pandemic but also maintain the change longer. Residents from lower-income regions show a faster and greater hyperbolic decay, which we suggest may help account for different COVID-19 rates. Our model represents a powerful tool to understand and forecast mobility patterns post emergency, and thus to help produce more effective responses.
RNA m
6
A demethylase ALKBH5 regulates the development of γδ T cells
Authors: Ding Chenbo , Xu Hao , Yu Zhibin , Roulis Manolis , Qu Rihao , Zhou Jing , Oh Joonseok , Crawford Jason , Gao Yimeng , Jackson Ruaidhrí , Sefik Esen , Li Simiao , Wei Zheng , Skadow Mathias , Yin Zhinan , Ouyang Xinshou , Wang Lei , Zou Qiang , Su Bing , Hu Weiguo , Flavell Richard A. , Li Hua-Bing
Published: August 2022

γδ T cells are an abundant T cell population at the mucosa and are important in providing immune surveillance as well as maintaining tissue homeostasis. However, despite γδ T cells’ origin in the thymus, detailed mechanisms regulating γδ T cell development remain poorly understood.
N
6
-methyladenosine (m
6
A) represents one of the most common posttranscriptional modifications of messenger RNA (mRNA) in mammalian cells, but whether it plays a role in γδ T cell biology is still unclear. Here, we show that depletion of the m
6
A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells, which confers enhanced protection against gastrointestinal
Salmonella typhimurium
infection. Mechanistically, loss of ALKBH5 favors the development of γδ T cell precursors by increasing the abundance of m
6
A RNA modification in thymocytes, which further reduces the expression of several target genes including Notch signaling components
Jagged1
and
Notch2
. As a result, impairment of Jagged1/Notch2 signaling contributes to enhanced proliferation and differentiation of γδ T cell precursors, leading to an expanded mature γδ T cell repertoire. Taken together, our results indicate a checkpoint role of ALKBH5 and m
6
A modification in the regulation of γδ T cell early development.
dsRNA-induced condensation of antiviral proteins modulates PKR activity
Authors: Corbet Giulia A. , Burke James M. , Bublitz Gaia R. , Tay Jian Wei , Parker Roy
Published: August 2022

Mammalian cells respond to dsRNA in multiple manners. One key response to dsRNA is the activation of PKR, an eIF2α kinase, which triggers translational arrest and the formation of stress granules. However, the process of PKR activation in cells is not fully understood. In response to increased endogenous or exogenous dsRNA, we observed that PKR forms novel cytosolic condensates, referred to as dsRNA-induced foci (dRIFs). dRIFs contain dsRNA, form in proportion to dsRNA, and are enhanced by longer dsRNAs. dRIFs enrich several other dsRNA-binding proteins, including ADAR1, Stau1, NLRP1, and PACT. Strikingly, dRIFs correlate with and form before translation repression by PKR and localize to regions of cells where PKR activation is initiated. We hypothesize that dRIF formation is a mechanism that cells use to enhance the sensitivity of PKR activation in response to low levels of dsRNA or to overcome viral inhibitors of PKR activation.
Adrenergic receptor signaling induced by Klf15, a regulator of regeneration enhancer, promotes kidney reconstruction
Authors: Suzuki Nanoka , Kanai Akinori , Suzuki Yutaka , Ogino Hajime , Ochi Haruki
Published: August 2022

Despite the recent discovery of tissue regeneration enhancers in highly regenerative animals, upstream and downstream genetic programs connected by these enhancers still remain unclear. Here, we performed a genome-wide analysis of enhancers and associated genes in regenerating nephric tubules ofXenopus laevis. Putative enhancers were identified using assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) analyses. Their target genes were predicted based on their proximity to enhancers on genomic DNA and consistency of their transcriptome profiles to ATAC-seq/ChIP-seq profiles of the enhancers. Motif enrichment analysis identified the central role of Krüppel-like factors (Klf) in the enhancer. Klf15, a member of the Klf family, directly binds enhancers and stimulates expression of regenerative genes, includingadrenoreceptor alpha 1A(adra1a), whereas inhibition of Klf15 activity results in failure of nephric tubule regeneration. Moreover, pharmacological inhibition of Adra1a-signaling suppresses nephric tubule regeneration, while its activation promotes nephric tubule regeneration and restores organ size. These results indicate that Klf15-dependent adrenergic receptor signaling through regeneration enhancers plays a central role in the genetic network for kidney regeneration.
The circadian clock mediates daily bursts of cell differentiation by periodically restricting cell-differentiation commitment
Authors: Zhang Zhi-Bo , Sinha Joydeb , Bahrami-Nejad Zahra , Teruel Mary N.
Published: August 2022

Most mammalian cells have an intrinsic circadian clock that coordinates metabolic activity with the daily rest and wake cycle. The circadian clock is known to regulate cell differentiation, but how continuous daily oscillations of the internal clock can control a much longer, multiday differentiation process is not known. Here, we simultaneously monitor circadian clock and adipocyte-differentiation progression live in single cells. Strikingly, we find a bursting behavior in the cell population whereby individual preadipocytes commit to differentiate primarily during a 12-h window each day, corresponding to the time of rest. Daily gating occurs because cells irreversibly commit to differentiate within only a few hours, which is much faster than the rest phase and the overall multiday differentiation process. The daily bursts in differentiation commitment result from a differentiation-stimulus driven variable and slow increase in expression of PPARG, the master regulator of adipogenesis, overlaid with circadian boosts in PPARG expression driven by fast, clock-driven PPARG regulators such as CEBPA. Our finding of daily bursts in cell differentiation only during the circadian cycle phase corresponding to evening in humans is broadly relevant, given that most differentiating somatic cells are regulated by the circadian clock. Having a restricted time each day when differentiation occurs may open therapeutic strategies to use timed treatment relative to the clock to promote tissue regeneration.
Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1
Authors: Schwarz Madeline M. , Price David A. , Ganaie Safder S. , Feng Annie , Mishra Nawneet , Hoehl Ryan M. , Fatma Farheen , Stubbs Sarah H. , Whelan Sean P. J. , Cui Xiaoxia , Egawa Takeshi , Leung Daisy W. , Amarasinghe Gaya K. , Hartman Amy L.
Published: August 2022

Oropouche orthobunyavirus (OROV;
Peribunyaviridae
) is a mosquito-transmitted virus that causes widespread human febrile illness in South America, with occasional progression to neurologic effects. Host factors mediating the cellular entry of OROV are undefined. Here, we show that OROV uses the host protein low-density lipoprotein–related protein 1 (Lrp1) for efficient cellular infection. Cells from evolutionarily distinct species lacking Lrp1 were less permissive to OROV infection than cells with Lrp1. Treatment of cells with either the high-affinity Lrp1 ligand receptor-associated protein (RAP) or recombinant ectodomain truncations of Lrp1 significantly reduced OROV infection. In addition, chimeric vesicular stomatitis virus (VSV) expressing OROV glycoproteins (VSV-OROV) bound to the Lrp1 ectodomain in vitro. Furthermore, we demonstrate the biological relevance of the OROV-Lrp1 interaction in a proof-of-concept mouse study in which treatment of mice with RAP at the time of infection reduced tissue viral load and promoted survival from an otherwise lethal infection. These results with OROV, along with the recent finding of Lrp1 as an entry factor for Rift Valley fever virus, highlight the broader significance of Lrp1 in cellular infection by diverse bunyaviruses. Shared strategies for entry, such as the critical function of Lrp1 defined here, provide a foundation for the development of pan-bunyaviral therapeutics.
Regularly occurring bouts of retinal movements suggest an REM sleep–like state in jumping spiders
Authors: Rößler Daniela C. , Kim Kris , De Agrò Massimo , Jordan Alex , Galizia C Giovanni , Shamble Paul S.
Published: August 2022

Sleep and sleep-like states are present across the animal kingdom, with recent studies convincingly demonstrating sleep-like states in arthropods, nematodes, and even cnidarians. However, the existence of different sleep phases across taxa is as yet unclear. In particular, the study of rapid eye movement (REM) sleep is still largely centered on terrestrial vertebrates, particularly mammals and birds. The most salient indicator of REM sleep is the movement of eyes during this phase. Movable eyes, however, have evolved only in a limited number of lineages—an adaptation notably absent in insects and most terrestrial arthropods—restricting cross-species comparisons. Jumping spiders, however, possess movable retinal tubes to redirect gaze, and in newly emerged spiderlings, these movements can be directly observed through their temporarily translucent exoskeleton. Here, we report evidence for an REM sleep–like state in a terrestrial invertebrate: periodic bouts of retinal movements coupled with limb twitching and stereotyped leg curling behaviors during nocturnal resting in a jumping spider. Observed retinal movement bouts were consistent, including regular durations and intervals, with both increasing over the course of the night. That these characteristic REM sleep–like behaviors exist in a highly visual, long-diverged lineage further challenges our understanding of this sleep state. Comparisons across such long-diverged lineages likely hold important questions and answers about the visual brain as well as the origin, evolution, and function of REM sleep.
Examining atherosclerotic lesions in three dimensions at the nanometer scale with cryo-FIB-SEM
Authors: Capua-Shenkar Jenny , Varsano Neta , Itzhak Noya-Ruth , Kaplan-Ashiri Ifat , Rechav Katya , Jin Xueting , Niimi Manabu , Fan Jianglin , Kruth Howard S. , Addadi Lia
Published: August 2022

We employed in a correlative manner an unconventional combination of methods, comprising cathodoluminescence, cryo–scanning electron microscopy (SEM), and cryo–focused ion beam (FIB)-SEM, to examine the volumes of thousands of cubed micrometers from rabbit atherosclerotic tissues, maintained in close-to-native conditions, with a resolution of tens of nanometers. Data from three different intralesional regions, at the media–lesion interface, in the core, and toward the lumen, were analyzed following segmentation and volume or surface representation. The media–lesion interface region is rich in cells and lipid droplets, whereas the core region is markedly richer in crystals and has lower cell density. In the three regions, thin crystals appear to be associated with intracellular or extracellular lipid droplets and multilamellar bodies. Large crystals are independently positioned in the tissue, not associated with specific cellular components. This extensive evidence strongly supports the idea that the lipid droplet surfaces and the outer membranes of multilamellar bodies play a role in cholesterol crystal nucleation and growth and that crystal formation occurs, in part, inside cells. The correlative combination of methods that allowed the direct examination of cholesterol crystals and lipid deposits in the atherosclerotic lesions may be similarly used for high-resolution examination of other tissues containing pathological or physiological cholesterol deposits.
DARPP32, a target of hyperactive mTORC1 in the retinal pigment epithelium
Authors: Cai Jiyang , Litwin Christopher , Cheng Rui , Ma Jian-Xing , Chen Yan
Published: August 2022

The mechanistic target of rapamycin (mTOR) is assembled into signaling complexes of mTORC1 or mTORC2, and plays key roles in cell metabolism, stress response, and nutrient and growth factor sensing. Accumulating evidence from human and animal model studies has demonstrated a pathogenic role of hyperactive mTORC1 in age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) is a primary injury site in AMD. In mouse models of RPE-specific deletion of Tuberous sclerosis 1 (
Tsc1
), which encodes an upstream suppressor of mTORC1, the hyperactivated mTORC1 metabolically reprogrammed the RPE and led to the degeneration of the outer retina and choroid (CH). In the current study, we use single-cell RNA sequencing (scRNA-seq) to identify an RPE mTORC1 downstream protein, dopamine- and cyclic AMP-regulated phosphoprotein of molecular weight 32,000 (DARPP-32). DARPP-32 was not found in healthy RPE but localized to drusen and basal linear deposits in human AMD eyes. In animal models, overexpressing DARPP-32 by adeno-associated virus (AAV) led to abnormal RPE structure and function. The data indicate that DARPP-32 is a previously unidentified signaling protein subjected to mTORC1 regulation and may contribute to RPE degeneration in AMD.
Muscle degeneration in chronic massive rotator cuff tears of the shoulder: Addressing the real problem using a graphene matrix
Authors: Saveh Shemshaki Nikoo , Kan Ho-Man , Barajaa Mohammed , Otsuka Takayoshi , Lebaschi Amir , Mishra Neha , Nair Lakshmi S. , Laurencin Cato T.
Published: August 2022

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation in vitro and 2) the ability of GnP matrices to reverse muscle degenerative changes in vivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration.
Dialogic hypertextuality
Authors: Arnett Ronald C.
Published: August 2022

This essay demarcates between and among schools of dialogue, differentiating relational points of meaning origins. Contrasting dialogic roots constitute distinctions in social meaning and signification. Schools of dialogue embrace the relational interplay of address and response, with exchanges consisting of multiple simultaneous conversations. Their co-presence announces dialogic hypertextuality, which acknowledges and affirms multiple simultaneous conversations and meanings within a given encounter. No single interpreter or meaning captures dialogic existence; meanings push the boundaries of any exchange, before, during, and after. Dialogic exchanges embody multiple discourses that call forth distinctive dimensions of meaning. As one speaks, multiple conversations, inclusive of previous and anticipatory dialogues, shape us. Conversation between and among persons dwells within an existential reality of dialogic hypertextuality.
Autologous K63 deubiquitylation within the BRCA1-A complex licenses DNA damage recognition
Authors: Jiang Qinqin , Foglizzo Martina , Morozov Yaroslav I. , Yang Xuejiao , Datta Arindam , Tian Lei , Thada Vaughn , Li Weihua , Zeqiraj Elton , Greenberg Roger A.
Published: August 2022

The BRCA1-A complex contains matching lysine-63 ubiquitin (K63-Ub) binding and deubiquitylating activities. How these functionalities are coordinated to effectively respond to DNA damage remains unknown. We generated Brcc36 deubiquitylating enzyme (DUB) inactive mice to address this gap in knowledge in a physiologic system. DUB inactivation impaired BRCA1-A complex damage localization and repair activities while causing early lethality when combined with Brca2 mutation. Damage response dysfunction in DUB-inactive cells corresponded to increased K63-Ub on RAP80 and BRCC36. Chemical cross-linking coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and cryogenic-electron microscopy (cryo-EM) analyses of isolated BRCA1-A complexes demonstrated the RAP80 ubiquitin interaction motifs are occupied by ubiquitin exclusively in the DUB-inactive complex, linking auto-inhibition by internal K63-Ub chains to loss of damage site ubiquitin recognition. These findings identify RAP80 and BRCC36 as autologous DUB substrates in the BRCA1-A complex, thus explaining the evolution of matching ubiquitin-binding and hydrolysis activities within a single macromolecular assembly.
Numerical study on imaging of magnetic nanoparticles with ultrasound based on saturation magnetization
Authors: Yan Xiaoheng , Li Jun , Xu Hong , Yang Yanju , Lv Jingxiang
Published: August 2022

Imaging of magnetic nanoparticles with ultrasound utilizes ultrasound excitation and electromagnetic receiving. At present, the size of magnetic nanoparticles (MNPs) for the imaging method is required to be no less than 100 nm, which limits its application in human bodies. To overcome the limitation of particle size, imaging of MNPs with ultrasound based on saturation magnetization is proposed. The relationship between the concentration of superparamagnetic pear-shaped MNPs and the induced voltage under saturation magnetization is derived based on the classical Langevin theory of paramagnetism. A 3D simulation model is constructed and numerical research is carried out under the saturated magnetic field provided by the Helmholtz coil. The concentration image is reconstructed by point-by-point scanning. Numerical studies show that the induced voltage is rich in the concentration information of superparamagnetic pear-shaped MNPs, proving the feasibility of the method. The maximum induced voltage, which enhances the imaging effect, occurs under the minimum radius of the detection coil containing the region of interest. MNPs under 20 nm still meet the imaging requirements in the proposed method. This research pushes the imaging of MNPs with ultrasound based on saturation magnetization a further step forward to practical applications in the biomedical field.
Electrical transport properties of nanocrystalline and bulk nickel ferrite using complex impedance spectroscopy: a comparative study
Authors: Paswan Sanjeet Kumar , Pradhan Lagen Kumar , Kumar Pawan , Kumari Suman , Kar Manoranjan , Kumar Lawrence
Published: August 2022

In this work, the comparative study on the electrical transport properties of nanocrystalline nickel ferrite (NiFe2O4) and its bulk counterpart has been carried out in detail by using complex impedance spectroscopy in a wide range of frequencies (100 Hz–1 MHz) and temperatures (40 °C–320 °C). The dispersive nature of the dielectric constant and loss factor is explained by the Maxwell-Wagner model and Koop’s phenomenological theory. The value of the dielectric constant for nanocrystalline nickel ferrite is found to be more as compared to its bulk counterpart. The frequency variation dielectric permittivity is well fitted with the modified Debye formula, which suggests the presence of multiple relaxation processes. The temperature dependent ac conductivity follows Jonscher’s universal power law and reveals the presence of multiple transport mechanisms from small polaron hopping (SPH) to correlated barrier hopping (CBH) mechanism near 200 °C. The estimated values of Mott parameters are found to be satisfactory. Thermally activated relaxation phenomena have been confirmed by scaling curves of imaginary impedance (

Z
″

) and modulus (

M
″

). The comparison between the

Z
″

and

M
″

spectra indicates that both long-range and short-range movement of charge carriers contribute to dielectric relaxation with short-range charge carriers predominating at low temperatures while long-range charge carriers are dominating at high temperatures. Analysis of the semicircular arcs of Nyquist plot indicates the presence of grain boundary contribution to the electrical conduction process for the nanocrystalline sample at high temperatures. The non-Debye type of relaxation has been examined by stretching exponential factor (β) which has been estimated by fitting the modified KWW (Kohlrausch-Williams-Watts) equation to the imaginary electric modulus curve. The value of β is found to be strongly temperature dependent and its value for the nanocrystalline sample is less than that of the bulk system which is explained on the basis of dipole-dipole interaction.
Flavor-alignment in an S
3-symmetric Higgs sector and its RG-behavior*
Authors: Chakrabarty Nabarun , Chakraborty Indrani
Published: August 2022

A three Higgs-doublet model exhibiting

-symmetry can predict the observed pattern of quark masses and their mixings. However, the same symmetry also introduces potential flavor-changing neutral currents (FCNCs) at the tree level. In this study, we assume that the scalar potential contains appropriate soft

-breaking terms to maintain flexible choices of scalar masses. We identify the parameters in the Yukawa Lagrangian of the quark sector responsible for such FCNCs and constrain them using data from flavor physics observables, such as meson-decays and meson-mixings. We also validate the corresponding model parameter space via renormalization group evaluation.
Multi-feature computational framework for combined signatures of dementia in underrepresented settings
Authors: Moguilner Sebastian , Birba Agustina , Fittipaldi Sol , Gonzalez-Campo Cecilia , Tagliazucchi Enzo , Reyes Pablo , Matallana Diana , Parra Mario A , Slachevsky Andrea , Farías Gonzalo , Cruzat Josefina , García Adolfo , Eyre Harris A , La Joie Renaud , Rabinovici Gil , Whelan Robert , Ibáñez Agustín
Published: August 2022

Objective. The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD) remains challenging in underrepresented, underdiagnosed groups, including Latinos, as advanced biomarkers are rarely available. Recent guidelines for the study of dementia highlight the critical role of biomarkers. Thus, novel cost-effective complementary approaches are required in clinical settings. Approach. We developed a novel framework based on a gradient boosting machine learning classifier, tuned by Bayesian optimization, on a multi-feature multimodal approach (combining demographic, neuropsychological, magnetic resonance imaging (MRI), and electroencephalography/functional MRI connectivity data) to characterize neurodegeneration using site harmonization and sequential feature selection. We assessed 54 bvFTD and 76 AD patients and 152 healthy controls (HCs) from a Latin American consortium (ReDLat). Main results. The multimodal model yielded high area under the curve classification values (bvFTD patients vs HCs: 0.93 (±0.01); AD patients vs HCs: 0.95 (±0.01); bvFTD vs AD patients: 0.92 (±0.01)). The feature selection approach successfully filtered non-informative multimodal markers (from thousands to dozens). Results. Proved robust against multimodal heterogeneity, sociodemographic variability, and missing data. Significance. The model accurately identified dementia subtypes using measures readily available in underrepresented settings, with a similar performance than advanced biomarkers. This approach, if confirmed and replicated, may potentially complement clinical assessments in developing countries.
Floer cohomology and flips
Authors: Charest François , Woodward Chris
Published: August 2022

We show that blow-ups or reverse flips (in the sense of the minimal model program) of rational symplectic manifolds with point centers create Floer-non-trivial Lagrangian tori. These results are part of a conjectural decomposition of the Fukaya category of a compact symplectic manifold with a singularity-free running of the minimal model program, analogous to the description of Bondal-Orlov (Derived categories of coherent sheaves, 2002) and Kawamata (Derived categories of toric varieties, 2006) of the bounded derived category of coherent sheaves on a compact complex manifold.
CoCoA: conditional correlation models with association size
Authors: Tu Danni , Mahony Bridget , Moore Tyler M , Bertolero Maxwell A , Alexander-Bloch Aaron F , Gur Ruben , Bassett Dani S , Satterthwaite Theodore D , Raznahan Armin , Shinohara Russell T
Published: August 2022

Many scientific questions can be formulated as hypotheses about conditional correlations. For instance, in tests of cognitive and physical performance, the trade-off between speed and accuracy motivates study of the two variables together. A natural question is whether speed–accuracy coupling depends on other variables, such as sustained attention. Classical regression techniques, which posit models in terms of covariates and outcomes, are insufficient to investigate the effect of a third variable on the symmetric relationship between speed and accuracy. In response, we propose a conditional correlation model with association size, a likelihood-based statistical framework to estimate the conditional correlation between speed and accuracy as a function of additional variables. We propose novel measures of the association size, which are analogous to effect sizes on the correlation scale while adjusting for confound variables. In simulation studies, we compare likelihood-based estimators of conditional correlation to semiparametric estimators adapted from genomic studies and find that the former achieves lower bias and variance under both ideal settings and model assumption misspecification. Using neurocognitive data from the Philadelphia Neurodevelopmental Cohort, we demonstrate that greater sustained attention is associated with stronger speed–accuracy coupling in a complex reasoning task while controlling for age. By highlighting conditional correlations as the outcome of interest, our model provides complementary insights to traditional regression modeling and partitioned correlation analyses.
An algorithm for updating betweenness centrality scores of all vertices in a graph upon deletion of a single edge
Authors: Satotani Yoshiki , Migita Tsuyoshi , Takahashi Norikazu
Published: August 2022

Betweenness centrality (BC) is a measure of the importance of a vertex in a graph, which is defined using the number of the shortest paths passing through the vertex. Brandes proposed an efficient algorithm for computing the BC scores of all vertices in a graph, which accumulates pair dependencies while traversing single-source shortest paths. Although this algorithm works well on static graphs, its direct application to dynamic graphs takes a huge amount of computation time because the BC scores must be computed from scratch every time the structure of graph changes. Therefore, various algorithms for updating the BC scores of all vertices have been developed so far. In this article, we propose a novel algorithm for updating the BC scores of all vertices in a graph upon deletion of a single edge. We also show the validity and efficiency of the proposed algorithm through theoretical analysis and experiments using various graphs obtained from synthetic and real networks.
COVID-19 and the Impact on School-Based Mental Health Professionals
Authors: Knipp Hannah
Published: August 2022

In March of 2020, many school systems transitioned to fully virtual platforms in an attempt to stop the spread of COVID-19. In the following months, schools remained online, transitioned to hybrid (partially online, partially in-person) models, or reopened completely. School-based mental health professionals (SBMHPs) remained responsible for meeting the mental health needs of students in the school system, regardless of the setting. This study sought to find out how COVID-19 and the subsequent changes in school setting have impacted SBMHPs. Through ethnographic observations of a nonprofit providing school-based mental health services as well as qualitative interviews with SBMHPs, this study uncovered a range of impacts. SBMHPs experienced an increase in demand for support with meeting basic needs and improving attendance and academics. Further, SBMHPs continued to provide counseling and crisis response services; however, these services had to be significantly adapted for each unique school setting (virtual, hybrid, and in-person). Despite these significant role changes, SBMHPs were adaptive and continued to meet the needs of students.
Evolution of personality and locomotory performance traits during a late Pleistocene island colonization in a tree frog
Authors: Bisconti Roberta , Carere Claudio , Costantini David , Liparoto Anita , Chiocchio Andrea , Canestrelli Daniele
Published: August 2022

Recent empirical and theoretical studies suggest that personality and locomotory performance traits linked to dispersal abilities are crucial components of the dispersal syndromes, and that they can evolve during range expansions and colonization processes. Island colonization is one of the best characterized processes in dispersal biogeography, and its implication in the evolution of phenotypic traits has been investigated over a wide range of temporal scales. However, the effect of island colonization on personality and performance traits of natural populations, and how these traits could drive island colonization, has been little explored. Noteworthy, no studies have addressed these processes in the context of late Pleistocene range expansions. Here, we investigated the contribution of island colonization triggered by postglacial range expansions to intraspecific variation in personality and locomotory performance traits. We compared boldness, exploration, jumping performance, and stickiness abilities in populations from 3 equidistant areas of the Tyrrhenian tree frog Hyla sarda, 2 from the main island (Corsica Island), and 1 from the recently colonized island of Elba. Individuals from Elba were significantly bolder than individuals from Corsica, as they emerged sooner from a shelter (P = 0.028), while individuals from Corsica showed markedly higher jumping and stickiness performance (both P < 0.001), resulting as more performing than those of Elba. We discuss these results in the context of the major microevolutionary processes at play during range expansion, including selection, spatial sorting, founder effects, and their possible interaction with local adaptation processes.
Diverticular disease in a pediatric patient with Crohn’s disease mimicking a perforated post-appendectomy appendiceal stump
Authors: de Nanassy Joseph , Mack David , Bettolli Marcos , Sergi Consolato M
Published: August 2022

We present the finding of a diverticulum in the colonic wall of the cecum, arising in the context of ileocecal stricture in a child with Crohn disease mimicking a post-appendectomy perforated appendiceal stump. To our knowledge, a non-Meckel diverticulum in a pediatric patient with Crohn disease has not yet been reported and we examine the mechanics behind it. According to the Laplace Law, the pressure inside a container with curved walls is inversely proportional to its radius. A diverticulum forms at the point of maximum stricture and at the locus of least resistance (weakness) in the bowel wall due to the inflammatory bowel disease. The long-time interval between diagnosis of ileocecal stricture and surgery (9 months) is important to allow the formation of this diverticulum. Continued follow-up in adulthood is warranted due to an increased risk of intestinal diverticular disease and neoplasms in patients with Crohn disease.
Steady Normal-Mode Vortices in Circular Cavities
Authors: Tyvand Peder A
Published: August 2022

This article establishes elementary families of steady two-dimensional (2D) vortices in circular enclosures filled with inviscid fluid. A normal-mode vortex is a continuous vortex that satisfies a Helmholtz equation for the streamfunction. An individual normal-mode vortex satisfies the steady 2D vorticity equation. A way to satisfy the vorticity equation with two superposed normal-mode vortices is to let one of them have circular streamlines, trivially satisfying the kinematic boundary condition at the circle boundary. The requirement for steady flow is that the wavenumber eigenvalues for the Helmholtz equations are identical. This eigenvalue has to be dictated by a normal-mode vortex that is fully 2D. In a circle sector with a designed angle, it is possible to add two fully 2D normal-mode vortices so that their superposed flow is steady. One such example is demonstrated, where the circle sector has an angle of $63.77^\circ$. While conventional stability analysis does not apply to these families of steady normal-mode vortices, there is a latent algebraic instability in terms of linearly growing offspring vortices evolving from an initial state where a small initial perturbation is added to the steady normal-mode vortex.
Differentiated Egalitarianism: The Impact of Paid Family Leave Policy on Women’s and Men’s Paid and Unpaid Work
Authors: Gonalons-Pons Pilar
Published: August 2022

The birth of a new child continues to exacerbate gender specialization among different-sex couples. This study considers the potential of paid leave policies to intervene in this key life-course juncture and promote greater gender equality in paid and unpaid work. While previous research has examined the impact of paid leave policies on paid or unpaid work among mothers or fathers separately, this study provides an integrated framework and examines comprehensively how these benefits shape both mothers' and fathers' paid and unpaid work outcomes. I use data from the Current Population Survey 1990–2020 and the American Time Use Survey 2003–2019 and quasi-experimental differences-in-differences models to examine the impact of the introduction of paid leave policies in California and New Jersey. The results show that the policy increased mothers’ and fathers’ short-term time off from paid work after new births, increased mothers’ care work more than fathers’, and increased fathers’ housework more than mothers’. I call this pattern differentiated egalitarianism, denoting changes increasing men’s involvement in housework while simultaneously reproducing mothers’ primary caregiver role.
Prevention of heart failure, tachyarrhythmias and sudden cardiac death in HIV
Authors: Wu Katherine C. , Woldu Bethel , Post Wendy S. , Hays Allison G.
Published: August 2022

Purpose of review

To summarize the state-of-the-art literature on the epidemiology, disease progression, and mediators of heart failure, tachyarrhythmias, and sudden cardiac death in people living with HIV (PLWH) to inform prevention strategies.

Recent findings

Recent studies corroborate the role of HIV as a risk enhancer for heart failure and arrhythmias, which persists despite adjustment for cardiovascular risk factors and unhealthy behaviors. Immune activation and inflammation contribute to the risk. Heart failure occurs more frequently at younger ages, and among women and ethnic minorities living with HIV, highlighting disparities. Prospective outcome studies remain sparse in PLWH limiting prevention approaches. However, subclinical cardiac and electrophysiologic remodeling and dysfunction detected by noninvasive testing are powerful disease surrogates that inform our mechanistic understanding of HIV-associated cardiovascular disease and offer opportunities for early diagnosis.

Aggressive control of HIV viremia and cardiac risk factors and abstinence from unhealthy behaviors remain treatment pillars to prevent heart failure and arrhythmic complications. The excess risk among PLWH warrants heightened vigilance for heart failure and arrhythmic symptomatology and earlier testing as subclinical abnormalities are common. Future research needs include identifying novel therapeutic targets to prevent heart failure and arrhythmias and testing of interventions in diverse groups of PLWH.
Addressing gaps in cardiovascular care for people with HIV: bridging scientific evidence and practice
Authors: Liu Albert , Feinstein Matthew
Published: August 2022

Purpose of review

People with HIV continue to have an excess burden of cardiovascular disease compared to the general population. The reasons for these disparities in cardiovascular disease include HIV-specific risk enhancers, traditional atherosclerotic cardiovascular disease risk factors, and sociodemographic disparities, all of which are ripe targets for intervention.

Recent findings

Accurate risk prediction of atherosclerotic cardiovascular disease remains difficult, and cardiovascular risk for people with HIV may be underestimated in the absence of HIV-specific risk enhancers. Despite this increased cardiovascular risk, people with HIV are undertreated and often placed on inadequate lipid lowering therapy. Structural racism and HIV-related stigma play a role, and provider-level and structural-level interventions to encourage early identification and treatment of persons at high risk are necessary.

Persons with HIV should be screened with existing cardiovascular risk prediction tools, and those at high risk cardiovascular disease should be promptly referred for lifestyle and pharmacologic interventions as appropriate. System-level implementation research is ongoing in attempts to narrow the gap in cardiovascular care, particularly for vulnerable communities in low resource settings.
HIV and cardiovascular disease: the role of inflammation
Authors: Dirajlal-Fargo Sahera , Funderburg Nicholas
Published: August 2022

Purpose of review

HIV and antiretroviral therapy (ART) use are linked to an increased incidence of atherosclerotic cardiovascular disease (ASCVD). Immune activation persists in ART-treated people with HIV (PWH), and markers of inflammation (i.e. IL-6, C-reactive protein) predict mortality in this population. This review discusses underlying mechanisms that likely contribute to inflammation and the development of ASCVD in PWH.

Recent findings

Persistent inflammation contributes to accelerated ASCVD in HIV and several new insights into the underlying immunologic mechanisms of chronic inflammation in PWH have been made (e.g. clonal haematopoiesis, trained immunity, lipidomics). We will also highlight potential pro-inflammatory mechanisms that may differ in vulnerable populations, including women, minorities and children.

Mechanistic studies into the drivers of chronic inflammation in PWH are ongoing and may aid in tailoring effective therapeutic strategies that can reduce ASCVD risk in this population. Focus should also include factors that lead to persistent disparities in HIV care and comorbidities, including sex as a biological factor and social determinants of health. It remains unclear whether ASCVD progression in HIV is driven by unique mediators (HIV itself, ART, immunodeficiency), or if it is an accelerated version of disease progression seen in the general population.
Blood Reflux Through a PreserFlo MicroShunt Device After Needling
Authors: Cassottana Paola , Di Mola Ilaria , Ferro Desideri Lorenzo , Vagge Aldo , Cutolo Carlo A. , Traverso Carlo E. , Iester Michele
Published: August 2022

Introduction:

To report a case of hyphema after a bleb needling revision in a PreserFlo MicroShunt implantation.

Case Description:

An 87-year-old man suffering from bilateral open angle glaucoma was referred to our hospital with a diagnosis of unsatisfactory intraocular pressure (IOP) control in the right eye, despite the maximally tolerated medical therapy. The patient underwent PreserFlo MicroShunt implantation in his right eye. About 2 months after the surgical procedure, the IOP was raised because of bleb failure for subconjunctival scarring. A needling revision was performed at the slit lamp. During the procedure blood reflux through a PreserFlo MicroShunt device from a filtering bleb to the anterior chamber was observed, causing an IOP rise. Treatment with oral acetazolamide, topical steroid, and antibiotic resulted in the complete resolution of the hyphema in 2 weeks and a significant lowering in IOP.

Conclusions:

This is the first reported case of blood reflux to the anterior chamber through a PreserFlo MicroShunt implant after a needling procedure.
How to Do It: A Safe Bedside Protocol for Dual-Lumen Right Internal Jugular Cannulation for Venovenous Extracorporeal Membrane Oxygenation in COVID-19 Patients With Severe Acute Respiratory Distress Syndrome
Authors: Cha Stephanie , Kim Bo S. , Ha Jinny S. , Bush Errol L.
Published: August 2022

In appropriately selected patients with COVID-19 acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (VV ECMO) may offer a promising bridge to lung recovery or lung transplantation if lung recovery fails. Although the cannulation technique for VV ECMO via a right internal jugular (RIJ) dual-lumen catheter (DLC) requires expertise and guidance by either fluoroscopy or transesophageal echocardiography (TEE), it offers theoretical circulatory support advantages by using bicaval venous drainage to deliver oxygenated blood systemically with minimal recirculation as compared with the femoral vein and RIJ dual-site cannula configuration. In addition, patients are often too unstable to transport safely to an operating room or catheterization laboratory, and fluoroscopy is not always readily available to guide RIJ DLC placement. Here, we provide a comprehensive description of a safe, bedside protocol for VV ECMO cannulation via a RIJ DLC under TEE guidance. We will report our center’s experience (March 30, 2020 to November 21, 2021) and discuss important hemodynamic, safety, and infection control considerations.
Epidemiology and real-life experience in progressive pulmonary fibrosis
Authors: Valenzuela Claudia , Cottin Vincent
Published: August 2022

Purpose of review

Idiopathic pulmonary fibrosis (IPF), characterized by relentless disease progression from the time of diagnosis, is part of a larger group of chronic fibrosing interstitial lung diseases (ILDs). A proportion of patients with non-IPF ILDs may develop, despite conventional treatment, a progressive pulmonary fibrosis (PPF), also referred to as ILD with a progressive fibrosing phenotype (PF-ILD). These patients experience worsening of respiratory symptoms, decline in lung function, and early mortality. The goal of this review is to describe the epidemiology and recent real-life cohorts of PF-ILD, with implications for management.

Recent findings

The relatively new concept of PF-ILD has aroused active clinical research over the past years. To understand risk factors for progression and the real burden of the disease is crucial to improve management. In the last 2 years, different cohort studies have addressed these questions. They showed that almost one-third of the non-IPF fibrotic ILD patients develop PF-ILD or PPF.

Emerging data show similarities in prognosis between patients with IPF or with non-IPF PF-ILD patients. Early detection and appropriate treatment of this group of patients is a priority. Further research is needed to identify risk factors of progression, to clarify the assessment of progression in clinical practice, for a better management of patients with PF-ILD in a real-world setting.