bluuebunny/crossref_metadata_2025 huggingface dataset:
PHI-base in 2022: a multi-species phenotype database for Pathogen–Host Interactions
Authors: Urban Martin , Cuzick Alayne , Seager James , Wood Valerie , Rutherford Kim , Venkatesh Shilpa Yagwakote , Sahu Jashobanta , Iyer S Vijaylakshmi , Khamari Lokanath , De Silva Nishadi , Martinez Manuel Carbajo , Pedro Helder , Yates Andrew D , Hammond-Kosack Kim E
Published: November 2021

Since 2005, the Pathogen–Host Interactions Database (PHI-base) has manually curated experimentally verified pathogenicity, virulence and effector genes from fungal, bacterial and protist pathogens, which infect animal, plant, fish, insect and/or fungal hosts. PHI-base (www.phi-base.org) is devoted to the identification and presentation of phenotype information on pathogenicity and effector genes and their host interactions. Specific gene alterations that did not alter the in host interaction phenotype are also presented. PHI-base is invaluable for comparative analyses and for the discovery of candidate targets in medically and agronomically important species for intervention. Version 4.12 (September 2021) contains 4387 references, and provides information on 8411 genes from 279 pathogens, tested on 228 hosts in 18, 190 interactions. This provides a 24% increase in gene content since Version 4.8 (September 2019). Bacterial and fungal pathogens represent the majority of the interaction data, with a 54:46 split of entries, whilst protists, protozoa, nematodes and insects represent 3.6% of entries. Host species consist of approximately 54% plants and 46% others of medical, veterinary and/or environmental importance. PHI-base data is disseminated to UniProtKB, FungiDB and Ensembl Genomes. PHI-base will migrate to a new gene-centric version (version 5.0) in early 2022. This major development is briefly described.
Reasons for Preoperative Opioid Use Are Associated with Persistent Use following Surgery Among Patients Undergoing Total Knee and Hip Arthroplasty
Authors: Ervin-Sikhondze Brittany A , Moser Stephanie E , Pierce Jennifer , Dickens Joseph R , Lagisetty Pooja A , Urquhart Andrew G , Hallstrom Brian R , Brummett Chad M , McAfee Jenna
Published: November 2021

Objective

Most studies on preoperative opioid use only describe whether or not patients use opioids without characterizing reasons for use. Knowing why patients use opioids can help inform perioperative opioid management. The objective of this study was to explore pain specific reasons for preoperative opioid use prior to total hip and knee arthroplasty (THA and TKA) and their association with persistent use.

Methods

This is a prospective study of 197 patients undergoing THA (n = 99) or TKA (n = 98) enrolled in the Analgesic Outcomes Study between December 2015 and November 2018. All participants reported preoperative opioid use.

Results

Reasons for preoperative opioid use were categorized as surgical site pain only (81 [41.1%]); pain in other body areas only (22 [11.2%]); and combined pain (94 [47.7%]). Compared to patients taking opioids for surgical site pain, those with combined reasons for use had 1.24 (P = .40) and 2.28 (P = .16) greater odds of persistent use at 3 and 6 months postoperatively, adjusting for relevant covariates.

Conclusions

This study provides novel insights into the heterogeneity of reasons for presurgical opioid use in patients undergoing a THA or TKA. One key take away is that not all preoperative opioid use is the same and many patients are taking opioids preoperatively for more than just pain at the surgical site. Combined reasons for use was associated with long-term use, suggesting nonsurgical pain, in part, drives persistent opioid use after surgery. Future directions in perioperative care should focus on pain and non-pain reasons for presurgical opioid use to create tailored postoperative opioid weaning plans.
New magic textures of Majorana neutrinos and the baryon asymmetry of the Universe
Authors: Hyodo Yuta , Kitabayashi Teruyuki
Published: November 2021

The magic texture is one of the successful textures of the flavor neutrino mass matrix for Majorana neutrinos. In this paper, it turns out that two new types of magic textures are also consistent with neutrino oscillation experiments, observation of cosmic microwave background radiation, and neutrinoless double beta decay experiments. The connection between these new magic textures and the leptogenesis scenario for the origin of the baryon asymmetry of the Universe is also discussed.
Pathways and obstacles to social recovery following the elimination of SARS-CoV-2 from Aotearoa New Zealand: a qualitative cross-sectional study
Authors: Long Nicholas J , Appleton Nayantara Sheoran , Davies Sharyn Graham , Deckert Antje , Fehoko Edmond , Holroyd Eleanor , Martin-Anatias Nelly , Sterling Rogena , Trnka Susanna , Tunufa’i Laumua
Published: November 2021

Background

Many public health experts have claimed that elimination strategies of pandemic response allow ‘normal social life’ to resume. Recognizing that social connections and feelings of normality are important for public health, this study examines whether, and for whom, that goal is realized, and identifies obstacles that may inhibit its achievement.

Methods

Thematic analysis of narratives obtained via a qualitative cross-sectional survey of a community cohort in Aotearoa | New Zealand.

Results

A majority of participants reported that life after elimination was ‘more or less the same’ as before the pandemic. Some became more social. Nevertheless, a sizeable minority reported being less social, even many months after elimination. Key obstacles to social recovery included fears that the virus was circulating undetected and the enduring impact of lockdowns upon social relationships, personal habits and mental health. Within our sample, old age and underlying health conditions were both associated with a propensity to become less social.

Conclusions

Elimination strategies can successfully allow ‘normal social life’ to resume. However, this outcome is not guaranteed. People may encounter difficulties with re-establishing social connections in Zero-COVID settings. Measures designed to overcome such obstacles should be an integral part of elimination strategies.
Working Remotely and the Supply-Side Impact of COVID-19
Authors: Papanikolaou Dimitris , Schmidt Lawrence D W
Published: November 2021

We analyze the supply-side disruptions associated with COVID-19. We find that sectors in which a higher fraction of the workforce is not able to work remotely experienced greater declines in employment and expected revenue growth, worse stock market performance, and higher likelihood of default. The stock market overweights low-exposure industries. Thus, our findings cast light on the disconnect between stock market indices and aggregate outcomes. We combine these ex ante heterogeneous industry exposures with daily financial market data to create a stock return portfolio that tracks news about the supply-side disruptions resulting from the pandemic. (JEL G12, D22, H25, J20, E00)
Examining Parent Adverse Childhood Experiences as a Distal Risk Factor in Pediatric Chronic Pain
Authors: Beveridge Jaimie K. , Yeates Keith O. , Madigan Sheri , Stone Amanda L. , Wilson Anna C. , Sumpton Janice E. , Salberg Sabrina , Mychasiuk Richelle , Noel Melanie
Published: November 2021

Objectives:

Adverse childhood experiences (ACEs; ie, exposure to abuse, neglect, household dysfunction in childhood) are associated with poor mental and physical health outcomes across the lifespan. Emerging research suggests parent ACEs also confer risk for poor child outcomes. The relation between parent ACEs and child pain in youth with chronic pain has not yet been examined. The aim of the current longitudinal study was to examine the associations among parent ACEs, parent health, and child pain, in a clinical sample of youth with chronic pain.

Methods:

In total, 192 youth (75.5% female, 10 to 18 y old) and one of their parents (92.2% female) were recruited from tertiary pediatric chronic pain clinics in Canada. At baseline, parents completed self-report measures of ACEs, chronic pain status, anxiety and depressive symptoms, and posttraumatic stress disorder symptoms. At a 3-month follow-up, youth completed self-report measures of pain intensity and pain interference.

Results:

Regression and mediation analyses revealed that parent ACEs significantly predicted parent chronic pain status and depressive symptoms, but not parent anxiety or posttraumatic stress disorder symptoms. Moreover, parent ACEs were not significantly related to youth pain, either directly or indirectly through parent health variables.

Discussion:

Findings suggest that an intergenerational cascade from parent ACEs to parent health to child pain was not present in the current sample. Further research that examines the role of parent ACEs in the development of child chronic pain, as well as other risk and resiliency factors that may mediate or moderate the association between parent ACEs and child chronic pain, is needed.
Acute Corneal Epithelial Rejection of LR-CLAL After SARS-CoV-2 Vaccination
Authors: de la Presa Martin , Govil Amit , Chamberlain Winston D. , Holland Edward J.
Published: November 2021

Purpose:

The purpose of this study was to report a case of acute corneal epithelial rejection of living-related conjunctival limbal allograft (LR-CLAL) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

Observations:

A 27-year-old woman developed acute epithelial rejection of LR-CLAL 2 weeks after receiving the SARS-CoV-2 vaccine. She received the LR-CLAL transplant 4 years and 7 months previously and had a stable clinical course with no history of rejection. She had an ABO blood group and human leukocyte antigen compatible donor, no systemic comorbidities, and no rejection risk factors.

Conclusions:

The novel SARS-CoV-2 vaccine upregulates the immune system to produce an adaptive immune response. The SARS-CoV-2 vaccine may potentially be associated with increased risk of rejection in those with ocular surface transplants.
Measuring G Protein Activation with Spectrally Resolved Fluorescence Fluctuation Spectroscopy
Authors: Foust Daniel J. , Piston David W.
Published: November 2021

G protein-coupled receptor signaling has been posited to occur through either collision coupling or pre-assembled complexes with G protein transducers. To investigate the dynamics of G protein signaling, we introduce fluorescence covariance matrix analysis (FCMA), a novel implementation of fluorescence cumulant analysis applied to spectrally resolved fluorescence images. We labeled the GPCR, Gα, and Gβγ units with distinct fluorescent protein labels and we applied FCMA to measure directly the complex formation during stimulation of dopamine and adrenergic receptors. To determine the prevalence of hetero-oligomers, we compared the GPCR data to those from control samples expressing three fluorescent protein labels with known stoichiometries. Interactions between Gα and Gβγ subunits determined by FCMA were sensitive to stimulation with GPCR ligands. However, GPCR/G protein interactions were too weak to be distinguished from background. These findings support a collision coupling mechanism rather than pre-assembled complexes for the two GPCRs studied.
The effect of the preceding masking noise on monaural and binaural release from masking
Authors: Kim Hyojin , Ratkute Viktorija , Epp Bastian
Published: November 2021

Auditory stream segregation can be facilitated when the maskers share coherent amplitude modulations or by utilizing spatial cues. The effectiveness of each cue can be quantified as a decrease in masked thresholds, termed as comodulated masking release (CMR) and binaural masking level difference (BMLD). Prolonged exposure to the masker can influence following target segregation. However, the collective impact preceding noise on target segregation in the presence of comodulation and interaural phase difference (IPD) cues is unclear. Stimuli were used to induce noise streams by altering the duration and temporal coherence of the envelope of the preceding masker. The effect on following target detection with CMR and BMLD induced by an IPD of the target tone was investigated. The results indicate that the effect of the preceding stream formation on CMR operates on different time scales, extending beyond 200 ms, depending on the spectrotemporal characteristics of the maskers. However, the effect on IPD-induced BMLD was not significant across time. Under the simplifying assumption that peripheral processing operates on shorter time scales than cortical processing, the results of the present study may provide insights into auditory signal processing in the presence of beneficial cues for target stream segregation.
Common resistance mechanisms are deployed by plants against sap-feeding herbivorous insects: insights from a meta-analysis and systematic review
Authors: Leybourne DJ , Aradottir GI
Published: November 2021

Sap-feeding insects cause significant yield losses to the world’s crops, these insects feed using syringe-like mouthparts and electrophysiology can be used to compare feeding behaviour on susceptible and resistant plants to identify the mechanistic processes behind resistant phenotypes. Data extracted from 129 studies, comprising 41 insect species across eight insect taxa and 12 host-plant families representing over 30 species, demonstrates that mechanisms deployed by resistant plants have common consequences on the feeding behaviour of diverse insect groups. We show that insects feeding on resistant plants take longer to establish a feeding site and have their feeding duration suppressed two-fold compared with insects feeding on susceptible plants. Our results reveal that the underlying traits contributing towards resistant phenotypes are conserved across plant families, deployed against taxonomically diverse insect groups, and that the underlying resistance mechanisms are conserved. These findings provide new insight that will be beneficial when developing future crop varieties.
Open-ended molecular recording of sequential cellular events into DNA
Authors: Loveless Theresa B. , Carlson Courtney K. , Dentzel Helmy Catalina A. , Hu Vincent J. , Ross Sara K. , Demelo Matt C. , Murtaza Ali , Liang Guohao , Ficht Michelle , Singhai Arushi , Pajoh-Casco Marcello J. , Liu Chang C.
Published: November 2021

Genetically encoded DNA recorders noninvasively convert transient biological events into durable mutations in a cell’s genome, allowing for the later reconstruction of cellular experiences using high-throughput DNA sequencing1. Existing DNA recorders have achieved high-information recording2–15, durable recording3,5–10,13,15–19, multiplexed recording of several cellular signals5–8,19,20, and temporally resolved signal recording5–8,19,20, but not all at the same time in mammalian cells. We present a DNA recorder called peCHYRON (prime editing21Cell HistorY Recording by Ordered iNsertion) that does. In peCHYRON, mammalian cells are engineered to express prime editor and a collection of prime editing guide RNAs21(pegRNAs) that facilitate iterative rounds of prime editing. In each round of editing, prime editor inserts a variable triplet DNA sequence alongside a constant propagator sequence that deactivates the previous and activates the next step of insertion. Editing can continue indefinitely because each insertion adds the complete sequence needed to initiate the next step. Because only one active target site is present at any given time, insertions accumulate sequentially, in a unidirectional order. Thus, temporal information is preserved in the order of insertions. Durability is achieved through the use of a prime editor that only nicks a single DNA strand, effectively avoiding deletion mutations that could otherwise corrupt the information stored at the recording locus. High-information content is established by co-expressing a variety of pegRNAs, each harboring unique triplet DNA sequences. We demonstrate that constitutive expression of such a library of pegRNAs generates insertion patterns that support straightforward reconstruction of cell lineage relationships. In an alternative pegRNA expression scheme, we also achieve multiplexed recording by manually pulsing expression of different pegRNAs, then reconstructing pulse sequences from the peCHYRON records. Additionally, we coupled the expression of specific pegRNAs to specific biological stimuli, which allowed temporally resolved, multiplexed recording of chemical exposures in populations of mammalian cells.

Graphical abstract
A framework for detecting noncoding rare variant associations of large-scale whole-genome sequencing studies
Authors: Li Zilin , Li Xihao , Zhou Hufeng , Gaynor Sheila M. , Selvaraj Margaret S. , Arapoglou Theodore , Quick Corbin , Liu Yaowu , Chen Han , Sun Ryan , Dey Rounak , Arnett Donna K. , Bielak Lawrence F. , Bis Joshua C. , Blackwell Thomas W. , Blangero John , Boerwinkle Eric , Bowden Donald W. , Brody Jennifer A. , Cade Brian E. , Conomos Matthew P. , Correa Adolfo , Cupples L. Adrienne , Curran Joanne E. , de Vries Paul S. , Duggirala Ravindranath , Freedman Barry I. , Göring Harald H. H. , Guo Xiuqing , Kalyani Rita R. , Kooperberg Charles , Kral Brian G. , Lange Leslie A. , Manichaikul Ani , Martin Lisa W. , Mitchell Braxton D. , Montasser May E. , Morrison Alanna C. , Naseri Take , O’Connell Jeffrey R. , Palmer Nicholette D. , Peyser Patricia A. , Psaty Bruce M. , Raffield Laura M. , Redline Susan , Reiner Alexander P. , Reupena Muagututi‘a Sefuiva , Rice Kenneth M. , Rich Stephen S. , Smith Jennifer A. , Taylor Kent D. , Vasan Ramachandran S. , Weeks Daniel E. , Wilson James G. , Yanek Lisa R. , Zhao Wei ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   TOPMed Lipids Working Group, Rotter Jerome I. , Willer Christen J. , Natarajan Pradeep , Peloso Gina M. , Lin Xihong
Published: November 2021

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare variants’ (RVs) associations with complex human traits. Variant set analysis is a powerful approach to study RV association, and a key component of it is constructing RV sets for analysis. However, existing methods have limited ability to define analysis units in the noncoding genome. Furthermore, there is a lack of robust pipelines for comprehensive and scalable noncoding RV association analysis. Here we propose a computationally-efficient noncoding RV association-detection framework that uses STAAR (variant-set test for association using annotation information) to group noncoding variants in gene-centric analysis based on functional categories. We also propose SCANG (scan the genome)-STAAR, which uses dynamic window sizes and incorporates multiple functional annotations, in a non-gene-centric analysis. We furthermore develop STAARpipeline to perform flexible noncoding RV association analysis, including gene-centric analysis as well as fixed-window-based and dynamic-window-based non-gene-centric analysis. We apply STAARpipeline to identify noncoding RV sets associated with four quantitative lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several noncoding RV associations in an additional 9,123 TOPMed samples.
Ancient mitogenomes unravel massive genetic diversity loss during near extinction of Alpine ibex
Authors: Robin Mathieu , Ferrari Giada , Akgül Gülfirde , von Seth Johanna , Schuenemann Verena J. , Dalén Love , Grossen Christine
Published: November 2021

Population bottlenecks can have dramatic consequences for the health and long-term survival of a species. A recent bottleneck event can also largely obscure our understanding of standing variation prior to the contraction. Historic population sizes can be modeled based on extant genomics, however uncertainty increases with the severity of the bottleneck. Integrating ancient genomes provides a powerful complement to retrace the evolution of genetic diversity through population fluctuations. Here, we recover 15 high-quality mitogenomes of the once nearly extinct Alpine ibex spanning 8601 ± 33 BP to 1919 CE and combine these with 60 published modern genomes. Coalescent demography simulations based on modern genomes indicate population fluctuations matching major climatic change over the past millennia. Using ancient genomes, we show that mitochondrial haplotype diversity has been reduced to a fifth of the pre-bottleneck diversity with several highly differentiated mitochondrial lineages having co-existed historically. The main collapse of mitochondrial diversity coincided with human settlement expansions in the Middle Ages. The near extinction severely reduced the mitochondrial diversity. After recovery, one lineage was spread and nearly fixed across the Alps due to recolonization efforts. Contrary to expectations, we show that a second ancestral mitochondrial lineage has survived in an isolated population further south. Our study highlights that a combined approach integrating genomic data of ancient, historic and extant populations unravels major long-term population fluctuations.
Interneuron Control of C. elegans Developmental Decision-making
Authors: Chai Cynthia M. , Torkashvand Mahdi , Seyedolmohadesin Maedeh , Park Heenam , Venkatachalam Vivek , Sternberg Paul W.
Published: November 2021

Animals integrate external stimuli to shape their physiological responses throughout development. In adverse environments, Caenorhabditis elegans larvae can enter a stress-resistant diapause state with arrested metabolism and reproductive physiology. Amphid sensory neurons feed into both rapid chemotactic and short-term foraging mode decisions, mediated by amphid and premotor interneurons, as well as the long-term diapause decision. We identify amphid interneurons that integrate pheromone cues and propagate this information via a neuropeptidergic pathways to influence larval developmental fate, bypassing the pre-motor system. AIA interneuron-derived FLP-2 neuropeptide signaling promotes reproductive growth and AIA activity is suppressed by pheromone. FLP-2 acts antagonistically to the insulin-like INS-1. FLP-2’s growth promoting effects are inhibited by upstream metabotropic glutamatergic signaling and mediated by the broadly-expressed neuropeptide receptor NPR-30. Conversely, the AIB interneurons and their neuropeptide receptor NPR-9/GALR2 promote diapause entry. These neuropeptidergic outputs allow reuse of parts of a sensory system for a decision with a distinct timescale.
Robust transcriptional profiling and identification of differentially expressed genes with low input RNA sequencing of adult hippocampal neural stem and progenitor populations
Authors: Denninger Jiyeon K. , Walker Logan A. , Chen Xi , Turkoglu Altan , Pan Alex , Tapp Zoe , Senthilvelan Sakthi , Rindani Raina , Kokiko-Cochran Olga , Bundschuh Ralf , Yan Pearlly , Kirby Elizabeth D.
Published: November 2021

Multipotent neural stem cells (NSCs) are found in several isolated niches of the adult mammalian brain where they have unique potential to assist in tissue repair. Modern transcriptomics offer high-throughput methods for identifying disease or injury associated gene expression signatures in endogenous adult NSCs, but they require adaptation to accommodate the rarity of NSCs. Bulk RNA sequencing (RNAseq) of NSCs requires pooling several mice, which impedes application to labor-intensive injury models. Alternatively, single cell RNAseq can profile hundreds to thousands of cells from a single mouse and is increasingly used to study NSCs. The consequences of the low RNA input from a single NSC on downstream identification of differentially expressed genes (DEGs) remains largely unexplored. Here, to clarify the role that low RNA input plays in NSC DEG identification, we directly compared DEGs in an oxidative stress model of cultured NSCs by bulk and single cell sequencing. While both methods yielded DEGs that were replicable, single cell sequencing DEGs derived from genes with higher relative transcript counts compared to all detected genes and exhibited smaller fold changes than DEGs identified by bulk RNAseq. The loss of high fold-change DEGs in the single cell platform presents an important limitation for identifying disease-relevant genes. To facilitate identification of such genes, we determined an RNA-input threshold that enables transcriptional profiling of NSCs comparable to standard bulk sequencing and used it to establish a workflow for in vivo profiling of endogenous NSCs. We then applied this workflow to identify DEGs after lateral fluid percussion injury, a labor-intensive animal model of traumatic brain injury. Our work suggests that single cell RNA sequencing may underestimate the diversity of pathologic DEGs but population level transcriptomic analysis can be adapted to capture more of these DEGs with similar efficacy and diversity as standard bulk sequencing. Together, our data and workflow will be useful for investigators interested in understanding and manipulating adult hippocampal NSC responses to various stimuli.
Determinants of functional synaptic connectivity among amygdala-projecting prefrontal cortical neurons
Authors: Printz Yoav , Patil Pritish , Mahn Mathias , Benjamin Asaf , Litvin Anna , Levy Rivka , Bringmann Max , Yizhar Ofer
Published: November 2021

The medial prefrontal cortex (mPFC) mediates a variety of complex cognitive functions via its vast and diverse connections with cortical and subcortical structures. Understanding the patterns of synaptic connectivity that comprise the mPFC local network is crucial for deciphering how this circuit processes information and relays it to downstream structures. To elucidate the synaptic organization of the mPFC, we developed a high-throughput optogenetic method for mapping large-scale functional synaptic connectivity. We show that mPFC neurons that project to the basolateral amygdala display unique spatial patterns of local-circuit synaptic connectivity within the mPFC, which distinguish them from the general mPFC cell population. Moreover, the intrinsic properties of the postsynaptic mPFC cell and anatomical position of both cells jointly account for ~7.5% of the variation in probability of connection between mPFC neurons, with anatomical distance and laminar position explaining most of this fraction in variation. Our findings demonstrate a functional segregation of mPFC excitatory neuron subnetworks, and reveal the factors determining connectivity in the mPFC.
Nuclear mRNA metabolism drives selective basket assembly on a subset of nuclear pores in budding yeast
Authors: Bensidoun Pierre , Reiter Taylor , Montpetit Ben , Zenklusen Daniel , Oeffinger Marlene
Published: November 2021

To determine which transcripts should reach the cytoplasm for translation, eukaryotic cells have established mechanisms to regulate selective mRNA export through the nuclear pore complex (NPC). The nuclear basket, a substructure of the NPC protruding into the nucleoplasm, is thought to function as a stable platform where mRNA-protein complexes (mRNPs) are rearranged and undergo quality control (QC) prior to export, ensuring that only mature mRNAs reach the cytoplasm. Here, we use proteomic, genetic, live-cell, and single-molecule resolution microscopy approaches in budding yeast to demonstrate that baskets assemble only on a subset of NPCs and that basket formation is dependent on RNA polymerase II (Pol II) transcription and subsequent mRNP processing. Specifically, we observe that the cleavage and polyadenylation machinery, the poly(A)-binding protein Pab1, and pre-mRNA-leakage factor Pml39 are required for basket assembly. We further show that while all nuclear pores can bind Mlp1, baskets assemble only on a subset of nucleoplasmic NPCs, and these basket-containing pores associate a distinct protein and RNA interactome. Taken together, our data points towards nuclear pore heterogeneity and an RNA-dependent mechanism for functionalization of nuclear pores in budding yeast through nuclear basket assembly.
Genotype-phenotype correlation analysis and therapeutic development using a patient stem cell-derived disease model of Wolfram syndrome
Authors: Kitamura Rie Asada , Maxwell Kristina G. , Ye Wenjuan , Kries Kelly , Brown Cris M , Augsornworawat Punn , Hirsch Yoel , Johansson Martin M , Weiden Tzvi , Ekstein Joseph , Cohen Joshua , Klee Justin , Leslie Kent , Simeonov Anton , Henderson Mark J. , Millman Jeffrey R. , Urano Fumihiko
Published: November 2021

Wolfram syndrome is a rare genetic disorder largely caused by pathogenic variants in the WFS1 gene and manifested by diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Recent genetic and clinical findings have revealed Wolfram syndrome as a spectrum disorder. Therefore, a genotype-phenotype correlation analysis is needed for diagnosis and therapeutic development. Here, we focus on the WFS1 c.1672C>T, p.R558C variant which is highly prevalent in the Ashkenazi-Jewish population. Clinical investigation indicates that subjects carrying the homozygous WFS1 c.1672C>T, p.R558C variant show mild forms of Wolfram syndrome phenotypes. Expression of WFS1 p.R558C is more stable compared to the other known recessive pathogenic variants associated with Wolfram syndrome. Stem cell-derived islets (SC-islets) homozygous for WFS1 c.1672C>T variant recapitulates genotype-related Wolfram phenotypes, which are milder than those of SC-islets with compound heterozygous WFS1 c.1672C>T (p.R558C), c.2654C>T (p.P885L). Enhancing residual WFS1 function by a combination treatment of chemical chaperones, sodium 4-phenylbutyrate (4-PBA) and tauroursodeoxycholic acid (TUDCA), mitigates detrimental effects caused by the WFS1 c.1672C>T, p.R558C variant and restored SC-islet function. Thus, the WFS1 c.1672C>T, p.R558C variant causes a mild form of Wolfram syndrome phenotypes, which can be remitted with a combination treatment of chemical chaperones. We demonstrate that our patient stem cell-derived disease model provides a valuable platform for further genotype-phenotype analysis and therapeutic development for Wolfram syndrome.

One sentence summary

Development of personalized therapy for Wolfram syndrome using genetics and iPSC model.
Moth species richness in an upland tropical rainforest: A citizen scientist assisted study
Authors: Tng David Y. P. , Apgaua Deborah M. G. , Fisher Nicholas J. , Fazio Victor W.
Published: November 2021

Diversity studies on moths in Australia are rare, presenting various shortfalls in knowledge that impedes and understanding of their biodiversity values and their conservation. In particular, the Wet Tropics of Australia deserves attention, given the paucity of systematic moth surveys in the region and its World Heritage Area status. To fill this knowledge gap, we conducted a study to observe moths on 191 nights over a main one-year survey period at an upland rainforest locality, and uploaded all observations on iNaturalist. We also compiled other incidental observations in the general locality by other observers and observations outside the survey period. In total, we document 4,434 observations of moths represented by 1041 distinct moth morphospecies. Of these, 703 are formally named species of moths, 146 to genus and 255 to higher taxonomic designations above genus level. Despite the rather intensive main survey effort, our results suggest that we have yet to reach a plateau in documenting the moth species richness of the locality. Using this study as a model, we show that the iNaturalist platform serves as an effective means to document and digitally curate biodiversity values at a locality, whilst providing complete data transparency and enabling broader community engagement of citizen scientists. We recommend the use of iNaturalist for future moth inventories, and as a resource for follow up meta-analyses of regional moth diversity and distributions.
Sincast: a computational framework to predict cell identities in single cell transcriptomes using bulk atlases as references
Authors: Deng Yidi , Choi Jarny , Lê Cao Kim-Anh
Published: November 2021

Characterizing the molecular identity of a cell is an essential step in single cell RNA-sequencing (scRNA-seq) data analysis. Numerous tools exist for predicting cell identity using single cell reference atlases. However, many challenges remain, including correcting for inherent batch effects between reference and query data and insufficient phenotype data from the reference. One solution is to project single cell data onto established bulk reference atlases to leverage their rich phenotype information.

Sincast is a computational framework to query scRNA-seq data based on bulk reference atlases. Prior to projection, single cell data are transformed to be directly comparable to bulk data, either with pseudo-bulk aggregation or graph-based imputation to address sparse single cell expression profiles. Sincast avoids batch effect correction, and cell identity is predicted along a continuum to highlight new cell states not found in the reference atlas.

In several case study scenarios, we show that Sincast projects single cells into the correct biological niches in the expression space of the bulk reference atlas. We demonstrate the effectiveness of our imputation approach that was specifically developed for querying scRNA-seq data based on bulk reference atlases. We show that Sincast is an efficient and powerful tool for single cell profiling that will facilitate downstream analysis of scRNA-seq data.
Therapeutic potential of macrophage colony-stimulating factor (CSF1) in chronic liver disease
Authors: Keshvari Sahar , Genz Berit , Teakle Ngari , Caruso Melanie , Cestari Michelle F. , Patkar Omkar L. , Tse Brian WC , Sokolowski Kamil A , Ebersbach Hilmar , Jascur Julia , MacDonald Kelli P. A. , Miller Gregory , Ramm Grant A. , Pettit Allison R. , Clouston Andrew D. , Powell Elizabeth E. , Hume David A. , Irvine Katharine M.
Published: November 2021

Resident and recruited macrophages control the development and proliferation of the liver. We showed previously in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, utilizing a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodeling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease.

Summary statement

Macrophages contribute to both progression and resolution of chronic tissue injury and fibrogenesis. Administration of a macrophage growth factor promoted liver regeneration and resolution of advanced liver fibrosis in mice.
MAP4K3 inhibits Sirtuin-1 to repress the LKB1-AMPK pathway to promote amino acid dependent activation of the mTORC1 complex
Authors: Branch Mary Rose , Hsu Cynthia L. , Ohnishi Kohta , Lee Elian , Meisenhelder Jill , Winborn Brett , Sopher Bryce L. , Taylor J. Paul , Hunter Tony , La Spada Albert R.
Published: November 2021

mTORC1 is the key rheostat controlling cellular metabolic state. Of the various inputs to mTORC1, the most potent effector of intracellular nutrient status is amino acid supply. Despite an established role for MAP4K3 in promoting mTORC1 activation in the presence of amino acids, the signaling pathway by which MAP4K3 controls mTORC1 activation remains unknown. Here we examined the process of MAP4K3 activation of mTORC1 and found that MAP4K3 represses the LKB1-AMPK pathway to prevent TSC1/2 complex inactivation of Rheb. When we sought the regulatory link between MAP4K3 and LKB1 inhibition, we discovered that MAP4K3 physically interacts with the master nutrient regulatory factor Sirtuin-1 and phosphorylates Sirtuin-1 to repress LKB1 activation. Our results reveal the existence of a novel signaling pathway linking amino acid satiety with MAP4K3-dependent suppression of SIRT1 to inactivate the repressive LKB1-AMPK pathway and thereby potently activate the mTORC1 complex to dictate the metabolic disposition of the cell.
The role of regulatory focus and team mindfulness in megaproject conflicts
Authors: Wang Dedong , Wang Yuxue
Published: November 2021

Purpose

Project conflicts are inevitable. Megaproject conflicts need to be managed across different levels. The purpose of this study is to investigate the role of individual-level regulatory focus and organization-level team mindfulness in managing megaproject conflicts.

Design/methodology/approach

By combining the individual motivation basis and organizational background of conflict resolution, this study constructed a multi-level structural equation model. The hypothesis is tested based on data collected from 182 respondents.

Findings

The findings of this study show that project manager's promotion focus has a direct positive effect on task conflict and a negative effect on relationship conflict. Prevention focus has a positive effect on relationship conflict and a negative effect on task conflict and process conflict. Team mindfulness has a negative effect on relationship conflict and process conflict and a positive effect on task conflict. Task conflict was negatively affected by the interaction between team mindfulness and promotion focus. The interaction between team mindfulness and prevention focus had a positive effect on relationship conflict.

Originality/value

This study verifies the positive role of project manager's promotion focus and prevention focus in conflict management and clarifies the strengthening role of team mindfulness in constructive conflict and the prevention role in destructive conflict. This study also confirms that team mindfulness can act as a reinforcement and complementary factor of regulatory focus in megaproject conflict, contributing to the current understanding of the project manager's role in megaproject mindfulness contexts.
Regulating non-financial reporting: evidence from European firms’ environmental, social and governance disclosures and earnings risk
Authors: Arif Muhammad , Gan Christohper , Nadeem Muhammad
Published: November 2021

Purpose

Motivated by the enactment of non-financial reporting regulations by the European Parliament, this paper aims to investigate the impact of European Union (EU) directive 2014/95/EU on the quantity of environmental, social and governance (ESG) disclosures by the S&P Europe 350 index firms. This study also investigates whether the implementation of the non-financial information (NFI) reporting regulations influences the association between ESG disclosures and firms’ earnings risk.

Design/methodology/approach

To measure the impact of mandatory regulations on the quantity of ESG disclosures, this study estimates the average treatment effects using a propensity weighted sample. Then this study uses the difference-in-differences method to estimate the differences in the association between ESG disclosures and earning risk before and after implementation of the EU directive.

Findings

The results show a significant positive impact of the EU directive on the quantity of ESG disclosures for the sample European public-interest entities, which indicates that the mandatory NFI reporting requirements could boost the availability of increasingly demanded ESG related information. The enhanced association between the ESG disclosures and firms’ earnings risk during the post-directive period reveals that mandating NFI reporting also increases the quality of ESG disclosures.

Originality/value

Using the legitimacy and decision-usefulness theories, this study provides novel evidence concerning the impact of the EU directive on the quantity and quality of ESG disclosures.
When consumers touch: a conceptual model of consumer haptic perception
Authors: Ranaweera Achini Tharaka
Published: November 2021

Purpose

Touch plays an important role in the evaluations of products. However, prior quantitative touch research does not present a holistic perspective of haptics. This study aims to provide a more comprehensive understanding of haptic information that consumers attain from touch.

Design/methodology/approach

Adopting a qualitative research approach, semi-structured, depth interviews were conducted with industry experts.

Findings

Based on the findings, this research proposes a conceptual model of consumer haptic perception consisting of seven key influences, namely, the effects of haptic sensation, haptic perception, the influence of individual factors, the influence of external environmental factors, the multi-dimensionality of haptics, haptic cue congruity and haptic dominance.

Practical implications

This study suggests firms to understand the importance of consumers’ haptic perception as an opportunity to engage an individual’s heart and mind through information attained through touch.

Originality/value

This is the first study in marketing to propose a conceptual model of haptics comprising several new haptic influences. This model contributes to the emerging literature of sensory marketing by providing directions for future touch research by capturing the dynamic nature of haptics.
Understanding the circumstances and stakeholder perceptions of gun violence restraining order use in California: A qualitative study
Authors: Pallin Rocco , Tomsich Elizabeth , Schleimer Julia P. , Pear Veronica A. , Charbonneau Amanda , Wintemute Garen J. , Knoepke Christopher E.
Published: November 2021

Research Summary

Risk‐based firearm removal policies are relatively new, and research on their implementation and effectiveness is limited. Using an interpretive phenomenological approach, we interviewed stakeholders in California's gun violence restraining order (GVRO) process to learn about circumstances in which GVROs are appropriate. Two primary themes emerged: (1) GVROs are most useful when there is acute risk of harm with a firearm, in the context of cognitive decline, or as related cases proceed through the courts, and (2) GVROs fill a gap in the policy landscape. Perceptions varied regarding the role of GVROs among preexisting violence prevention tools. Several informants perceived racial/ethnic disparities in GVRO use.

Policy Implications

Understanding practitioners’ perceptions of GVRO utility may help inform implementation and ensure that these policies equitably improve public health and safety. These results highlight the need for additional research on the impact of GVROs and possible disparities in use.
“Builders of a New Social Bond”: Fratelli Tutti on Good Politics and the Challenge of Inequality
Authors: Mulligan Suzanne
Published: November 2021

This article examines Pope Francis’s political vision as outlined in Fratelli Tutti, and argues that inequality presents a challenge to achieving what he calls “good politics.” Political trust is being eroded throughout the world due to corruption and rising economic disparities, with potentially damaging consequences for democratic politics. Inequality contributes to political instability since it weakens the common good, social solidarity, and critical citizenship. The social doctrine of the Catholic Church provides the context from which various forms of inequality will be examined, with particular focus on Fratelli Tutti.
The characteristics of residual pneumoperitoneum after laparoscopic colorectal surgery
Authors: Fukuhara Sotaro , Egi Hiroyuki , Kochi Masatoshi , Shimizu Wataru , Takakura Yuji , Taguchi Kazuhiro , Nakashima Ikki , Sumi Yusuke , Akabane Shintaro , Sato Koki , Yoshinaka Hisaaki , Teraoka Yoshifumi , Hattori Minoru , Ohdan Hideki
Published: November 2021

Introduction

Despite the popularity of laparoscopic surgery, it remains unclear whether residual pneumoperitoneum influences the patient's postoperative course. This study aimed to evaluate the characteristics of residual pneumoperitoneum.

Methods

This retrospective study included 201 Japanese patients who had undergone elective laparoscopic colorectal surgery. The patients were divided into groups, with and without anastomotic failure; the non‐anastomotic failure group was further divided into subgroups, with and without residual pneumoperitoneum. Patient characteristics were compared between the various groups.

Results

The group with residual pneumoperitoneum included 57 patients (30.3%). Percutaneous drainage was required for one patient with residual pneumoperitoneum. Univariate analyses revealed that residual pneumoperitoneum was associated with low values for body mass index (BMI) and subcutaneous fat area (SFA). Furthermore, relative to the group with anastomotic failure, the group without anastomotic failure but with residual pneumoperitoneum had lower values for inflammatory markers.

Conclusion

Low BMI and SFA values were identified as risk factors for residual pneumoperitoneum. Inflammatory markers may be useful as indicators for avoiding emergent surgery when it is difficult to differentiate between asymptomatic residual pneumoperitoneum and free air related to anastomotic failure.
Detecting colon polyps in endoscopic images using artificial intelligence constructed with automated collection of annotated images from an endoscopy reporting system
Authors: Hori Keisuke , Ikematsu Hiroaki , Yamamoto Yoichi , Matsuzaki Hiroki , Takeshita Nobuyoshi , Shinmura Kensuke , Yoda Yusuke , Kiuchi Takayoshi , Takemoto Satoko , Yokota Hideo , Yano Tomonori
Published: November 2021

Background

Artificial intelligence (AI) has made considerable progress in image recognition, especially in the analysis of endoscopic images. The availability of large‐scale annotated datasets has contributed to the recent progress in this field. Datasets of high‐quality annotated endoscopic images are widely available, particularly in Japan. A system for collecting annotated data reported daily could aid in accumulating a significant number of high‐quality annotated datasets.

Aim

We assessed the validity of using daily annotated endoscopic images in a constructed reporting system for a prototype AI model for polyp detection.

Methods

We constructed an automated collection system for daily annotated datasets from an endoscopy reporting system. The key images were selected and annotated for each case only during daily practice, not to be performed retrospectively. We automatically extracted annotated endoscopic images of diminutive colon polyps that had been diagnosed (study period March–September 2018) using the keywords of diagnostic information, and additionally collect the normal colon images. The collected dataset was devised into training and validation to build and evaluate the AI system. The detection model was developed using a deep learning algorithm, RetinaNet.

Results

The automated system collected endoscopic images (47,391) from colonoscopies (745), and extracted key colon polyp images (1356) with localized annotations. The sensitivity, specificity, and accuracy of our AI model were 97.0%, 97.7%, and 97.3% (n = 300), respectively.

Conclusion

The automated system enabled the development of a high‐performance colon polyp detector using images in endoscopy reporting system without the efforts of retrospective annotation works.