bluuebunny/crossref_metadata_2025 huggingface dataset:
Historic redlining, social mobility, and firearm violence
Authors: Poulson Michael R. , Neufeld Miriam Y. , LaRaja Alexander , Allee Lisa , Kenzik Kelly M. , Dechert Tracey
Published: August 2022

BACKGROUND

Much of the recorded medical literature focuses on individual-level factors that contribute to firearm violence. Recently, studies have highlighted higher incidence of firearm violence in historically redlined and marginalized areas, but few have gone on to study the downstream associations causing these differences. This study aims to understand the effects of historic redlining and current income mobility on firearm violence.

METHODS

Using a retrospective cross-sectional design, shooting incidents were spatially joined with redlining vector files and linked to income mobility data (how much a child makes in adulthood). Participants included all assault and homicide incidents involving a firearm in the city of Boston, between 2016 and 2019. The exposure of interest was redlining designation as outlined by the Home Owner's Loan Corporation (HOLC) in the 1930s and income mobility, stratified by race, defined as the income of a child in their 30s compared with where they grew up (census tract level). The outcome measured was shooting rate per census block.

RESULTS

We find that increases in Black income mobility (BIM) and White income mobility (WIM) are associated with significant decreases in rates of firearm incidents in all HOLC designations; however, there is a larger decrease with increasing BIM (relative risk, 0.47 per unit increase in BIM [95% confidence interval, 0.35–0.64]; relative risk, 0.81 per unit increase in WIM [95% confidence interval, 0.71–0.93]). Plotting predicted rates of firearm violence in each HOLC designation at different levels of BIM, there were no significant differences in shooting rates between historically harmful and beneficial classifications above $50,000 of BIM. Despite level of WIM, there were continued disparities between harmful and beneficial HOLC classification.

CONCLUSION

These findings highlight the importance of structural racism in the form of redlining and discriminatory housing policies, and the preclusion from economic mobility therein, on the incidence of firearm violence today.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Biomarkers of endothelial cell dysfunction persist beyond resuscitation in patients with hemorrhagic shock
Authors: Zeineddin Ahmad , Wu Feng , Chao Wei , Zou Lin , Vesselinov Roumen , Chipman Amanda M. , Dong Jing Fei , Huang Huang , Pati Shibani , Kozar Rosemary A.
Published: August 2022

BACKGROUND

It has been shown that microRNA-19b (miR-19b) binds to and degrades syndecan-1 after hemorrhagic shock (HS) and contributes to endothelial dysfunction in vitro and in vivo. The objective of the current study was to assess longitudinal changes in miR-19b and syndecan-1 in HS patients.

METHODS

Blood samples from HS patients (blood pressure <90 mm Hg and ≥2 U blood) were collected upon admission, completion of hemostasis, and after 24 hours for miR-19b (quantitative reverse transcription PCR) and syndecan-1 (enzyme-linked immunosorbent assay) and compared with controls and minimally injured (Injury Severity Score, ≤9). Inflammatory cytokines were measured (Luminex [Thermo Fisher, Waltham, MA]). Correlations between syndecan-1, miR-19b, inflammatory markers, and patient outcomes were performed. Logistic regression models were developed for outcomes.

RESULTS

Thirty-four HS patients were studied: age, 46 (19–89) years; male, 82%; penetrating, 35%; Injury Severity Score, 24 ± 10; and blood products at 24 hours, 21 ± 19 U. MicroRNA-19b was increased upon arrival and further increased over time: 4.6 → 6.7 → 24.1-fold change compared with 0.1 and 1.2 for minimally injured patients and controls, respectively. Syndecan-1 was increased to 42.6 → 50 → 51.5 ng/mL over time compared with 14.7 and 23.5 for minimally injured and controls, respectively. Values for both biomarkers remained significantly increased through 24 hours and were associated with a persistent increase in inflammatory cytokines. Admission syndecan-1 significantly predicted mortality, coagulopathy, and massive transfusion.

CONCLUSION

We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MicroRNA-19b did not demonstrate a strong correlation with syndecan-1 nor outcomes. Admission syndecan-1, however, remains a strong prognostic marker, but its elevation over time suggests a versatile role following HS that requires further investigation.

LEVEL OF EVIDENCE

Prognostic/Epidemiological; Level II.
Desensitization in Crossmatch-positive Kidney Transplant Candidates
Authors: Noble Johan , Jouve Thomas , Malvezzi Paolo , Rostaing Lionel
Published: August 2022

Access to kidney transplantation is limited by HLA-specific sensitization. Desensitization strategies enable crossmatch-positive kidney transplantation. In this review, we describe clinical experience gained over the last 20 y using desensitization strategies before kidney transplantation and describe the different tools used (both drugs and apheresis options), including IVIg, rituximab, apheresis techniques, interleukin-6 interference, proteasome inhibition, enzymatic degradation of HLA antibodies, complement inhibition, and B cytokine interference. Although access to transplantation for highly sensitized kidney transplantation candidates has been vastly improved by desensitization strategies, it remains, however, limited by the recurrence of HLA antibodies after transplantation and the occurrence of antibody-mediated rejection.
Are ape gestures like words? Outstanding issues in detecting similarities and differences between human language and ape gesture
Authors: Hobaiter Catherine , Graham Kirsty E. , Byrne Richard W.
Published: August 2022

Opinion piece: ape gestures are made intentionally, inviting parallels with human language; but how similar are their gestures to words? Here we ask this in three ways, considering: flexibility and ambiguity, first- and second-order intentionality, and usage in interactive exchanges. Many gestures are used to achieve several, often very distinct, goals. Such apparent ambiguity in meaning is potentially disruptive for communication, but—as with human language—situational and interpersonal context may largely resolve the intended meaning. Our evidence for first-order intentional use of gesture is abundant, but how might we establish a case for the second-order intentional use critical to language? Finally, words are rarely used in tidy signal–response sequences but are exchanged in back-and-forth interaction. Do gestures share this property? In this paper, we examine these questions and set out ways in which they can be resolved, incorporating data from wild chimpanzees.

This article is part of the theme issue ‘Cognition, communication and social bonds in primates’.
Communicative roots of complex sociality and cognition: preface to the theme issue
Authors: Roberts Sam G. B. , Dunbar Robin I. M. , Roberts Anna I.
Published: August 2022

Primates live in stable social groups in which they form differentiated relationships with group members and use a range of communication including facial expressions, vocalizations and gestures. However, how these different types of communication are used to regulate social interactions, and what cognitive skills underpin this communication, is still unclear. The aim of this special issue is to examine the types of cognitive skills underpinning the flexible and complex communication that is used to maintain the bonded social relationships found in primates and humans.

This article is part of the theme issue ‘Cognition, communication and social bonds in primates’.
Establishment of the Body Condition Score for adult female Xenopus laevis
Authors: Tix Leonie , Ernst Lisa , Bungardt Britta G. , Talbot Steven R. , Hilken Gero , Tolba René H.
Published: August 2022

The assessment of animals’ health and nutritional status using a Body Condition Score (BCS) has become a common and reliable tool in lab-animal science. It enables a simple, semi-objective, and non-invasive assessment (palpation of osteal prominences and subcutaneous fat tissue) in routine examination of an animal. In mammals, the BCS classification contains 5 levels: A low score describes a poor nutritional condition (BCS 1-2). A BCS of 3 to 4 is considered optimum, whereas a high score (BCS=5) is associated with obesity. While BCS are published for most common laboratory mammals, these assessment criteria are not directly applicable to clawed frogs (Xenopus laevis) due to their intracoelomic fat body instead of subcutaneous fat tissue. Therefore this assessment tool is still missing for Xenopus laevis.

The present study aimed to establish a species-specific BCS for clawed frogs in terms of experimental refinement. Accordingly, 62 adult female Xenopus laevis were weighed and sized. Further, the body contour was defined, classified, and assigned to BCS groups. A BCS 5 was associated with a mean body weight of 193.3 g (± 27.6 g), whereas a BCS 4 ranged at 163.1 g (±16.0 g). Animals with a BCS=3 had an average body weight of 114.7 g (±16.7 g). A BCS=2 was determined in 3 animals (103 g, 110 g, and 111 g). One animal had a BCS=1 (83 g), which would be equivalent to a humane endpoint.

In conclusion, individual examination using the presented visual BCS provides a quick and easy assessment of nutritional status and overall health of adult female Xenopus laevis. Due to their ectothermic nature and the associated special metabolic situation, it can be assumed that a BCS ≥3 is to be preferred for female Xenopus laevis. In addition, BCS assessment may indicate underlying subclinical health problems that require further diagnostic investigation.
Multiomics profiling of human plasma and CSF reveals ATN derived networks and highlights causal links in Alzheimer’s disease
Authors: Shi Liu , Xu Jin , Green Rebecca , Wretlind Asger , Homann Jan , Buckley Noel J. , Tijms Betty M. , Vos Stephanie J. B. , Lill Christina M. , Kate Mara ten , Engelborghs Sebastiaan , Sleegers Kristel , Frisoni Giovanni B. , Wallin Anders , Lleó Alberto , Pop Julius , Martinez-Lage Pablo , Streffer Johannes , Barkhof Frederik , Zetterberg Henrik , Visser Pieter Jelle , Lovestone Simon , Bertram Lars , Nevado-Holgado Alejo J. , Proitsi Petroula , Legido-Quigley Cristina
Published: August 2022

INTRODUCTION

This study employed an integrative system and causal inference approach to explore molecular signatures in blood and CSF, the Amyloid/Tau/Neurodegeneration [AT(N)] framework, MCI conversion to AD, and genetic risk for AD.

METHODS

Using the EMIF-AD MBD cohort, we measured 696 proteins in cerebrospinal fluid (n=371), 4001 proteins in plasma (n=972), 611 metabolites in plasma (n=696) and genotyped data in whole-blood (7,778,465 autosomal SNPs, n=936). We investigated associations: molecular modules to AT(N), module hubs with AD Polygenic Risk scores andAPOE4 genotypes, molecular hubs to MCI conversion and probed for causality with AD using Mendelian Randomization (MR).

RESULTS

AT(N) framework associated key hubs were mostly proteins and few lipids. In MR analyses, Proprotein Convertase Subtilisin/Kexin Type 7 showed weak causal associations with AD, and AD was causally associated with Reticulocalbin 2 and sphingomyelins.

DISCUSSION

This study reveals multi-omics networks associated with AT(N) and MCI conversion and highlights AD causal candidates.
Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial
Authors: Gálvez Nicolás MS , Pacheco Gaspar A , Schultz Bárbara M , Melo-González Felipe , Soto Jorge A , Duarte Luisa F , González Liliana A , Rivera-Pérez Daniela , Ríos Mariana , Berríos Roslye V , Vázquez Yaneisi , Moreno-Tapia Daniela , Vallejos Omar P , Andrade Catalina A , Hoppe-Elsholz Guillermo , Iturriaga Carolina , Urzua Marcela , Navarrete María S , Rojas Álvaro , Fasce Rodrigo , Fernández Jorge , Mora Judith , Ramírez Eugenio , Gaete-Argel Aracelly , Acevedo Mónica , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Weiskopf Daniela , Grifoni Alba , Sette Alessandro , Zeng Gang , Meng Weining ,   CoronaVac03CL Study Group, González-Aramundiz José V , Goldblatt David , González Pablo A , Abarca Katia , Bueno Susan M , Kalergis Alexis M
Published: August 2022

Background

The development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac®is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile.

Methods

This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac®separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured.

Results

Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-γ and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ secretion.

Conclusions

Immunization with CoronaVac®in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule.

Funding

Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile.

Clinical trial number

NCT04651790.

summary

Two immunization schedules were evaluated for the inactivated SARS-CoV-2 vaccine, Coronavac®, with two doses of the vaccine separated by two or four weeks. We compared humoral and cellular immune responses, showing they are mostly similar, with differences in neutralization capacities.
The thermodynamics of reproduction constrain species ranking dynamics and diversity
Authors: Froese Tom , Froese Rainer
Published: August 2022

Iñiguez, Pineda, Gershenson, and Barabási proposed that complex systems can be simplified and analyzed in terms of the dynamics of ordered lists. For social, economic, and infrastructural systems, they succeeded in modeling the dynamics of ranking with two mechanisms, namely displacement (i.e., shuffling of ranks among existing elements) and replacement of elements by new elements. A general pattern is that, for open systems with influx and outflux of elements, e.g., a list with a subset of elements, only the top of the list is stable; for closed systems, top and bottom are stable. This model was fitted to empirical data, resulting in a universal curve in which displacement and replacement parameters are inversely related, which implies that a single parameter could regulate both. Our aim is twofold: First, we demonstrate that the pattern generalizes to ranking of biological species, based on FishBase records of fish taxonomy and life history traits. Second, we propose a candidate for a unified mechanism, based on a recent model of the thermodynamics of self-replication.
Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: allosteric communications between and within viral and human proteins
Authors: Barozi Victor , Edkins Adrienne L. , Bishop Özlem Tastan
Published: August 2022

The interaction between the Spike (S) protein of SARS-CoV-2 and the human angiotensin converting enzyme 2 (hACE2) is essential for infection, and is a target for neutralizing antibodies. Consequently, selection of mutations in the S protein is expected to be driven by the impact on the interaction with hACE2 and antibody escape. Here, for the first time, we systematically characterized the collective effects of mutations in each of the Omicron sub-lineages (BA.1, BA.2, BA.3 and BA.4) on both the viral S protein receptor binding domain (RBD) and the hACE2 protein using post molecular dynamics studies and dynamic residue network (DRN) analysis. Our analysis suggested that Omicron sub-lineage mutations result in altered physicochemical properties that change conformational flexibility compared to the reference structure, and may contribute to antibody escape. We also observed changes in the hACE2 substrate binding groove in some sub-lineages. Notably, we identified unique allosteric communication paths in the reference protein complex formed by the DRN metricsbetweenness centralityandeigencentralityhubs, originating from the RBD core traversing the receptor binding motif of the S protein and the N-terminal domain of the hACE2 to the active site. We showed allosteric changes in residue network paths in both the RBD and hACE2 proteins due to Omicron sub-lineage mutations. Taken together, these data suggest progressive evolution of the Omicron S protein RBD in sub-lineages towards a more efficient interaction with the hACE2 receptor which may account for the increased transmissibility of Omicron variants.
Mouse lemur transcriptomic atlas informs primate genes, mutations, physiology, and disease
Authors:   The Tabula Microcebus Consortium, Ezran Camille , Liu Shixuan , Chang Stephen , Ming Jingsi , Guethlein Lisbeth A. , Wang Michael F.Z. , Dehghannasiri Roozbeh , Olivieri Julia , Frank Hannah K. , Tarashansky Alexander , Koh Winston , Jing Qiuyu , Botvinnik Olga , Antony Jane , Pisco Angela Oliveira , Karkanias Jim , Yang Can , Ferrell James E. , Boyd Scott D. , Parham Peter , Long Jonathan Z. , Wang Bo , Salzman Julia , De Vlaminck Iwijn , Wu Angela Ruohao , Quake Stephen R. , Krasnow Mark A.
Published: August 2022

Mouse lemurs (Microcebusspp.) are an emerging primate model organism. However, little is known about their genetics or cellular and molecular biology. In the accompanying paper, we used large-scale single cell RNA-sequencing of 27 organs and tissues to identify over 750 molecular cell types, characterize their full transcriptomic profiles, and study evolution of primate cell types. Here we use the atlas to characterize mouse lemur genes, mutations, physiology, and disease. We uncover thousands of previously unidentified lemur genes and hundreds of thousands of new splice junctions that globally define lemur gene structures and reveal over 85,000 primate splice junctions missing in mice. We systematically explore the lemur immune system, comparing the global expression profiles of key immune genes in health and disease, and molecular mapping of immune cell development, trafficking, and their local and global activation to infection. We characterize primate/lemur-specific physiology and disease including molecular features of the immune program, of lemur adipocytes that exhibit dramatic seasonal rhythms, and of metastatic endometrial cancer that resembles the human malignancy. We identify and describe the expression patterns of over 400 primate genes missing in mice, many with similar expression patterns in human and lemur and some implicated in human disease. Finally, we provide an experimental framework for reverse genetic analysis by identifying naturally-occurring nonsense (null) mutations in three primate genes missing in mice and analyzing their transcriptional phenotypes. This work establishes mouse lemur as a tractable primate model organism for genetic and molecular analysis, and it prioritizes primate genes, splice junctions, physiology, and disease for future study.
Myocardial deformation imaging by 2D speckle tracking echocardiography for assessment of diastolic dysfunction in murine cardiopathology
Authors: Daniels Lorna J. , Macindoe Calum , Koutsifeli Parisa , Annandale Marco , Raaijmakers Antonia J. A. , Weeks Kate L , Bell James R. , Janssens Johannes V. , Curl Claire L. , Delbridge Lea M.D. , Mellor Kimberley M.
Published: August 2022

Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.
Sensitive multimodal profiling of native DNA by transposase-mediated single-molecule sequencing
Authors: Nanda Arjun S , Wu Ke , Kasinathan Sivakanthan , Ostrowski Megan S , Clugston Andrew S , Satpathy Ansuman T , Sweet-Cordero E Alejandro , Goodarzi Hani , Ramani Vijay
Published: August 2022

We present SMRT-Tag: a multiplexable, PCR-free approach for constructing low-input, single-molecule Pacific Biosciences (PacBio) sequencing libraries through Tn5 transposition. As proof-of-concept, we apply SMRT-Tag to resolve human genetic and epigenetic variation in gold-standard human reference samples. SMRT-Tag requires 1-5% as much input material as existing protocols (15,000 – 50,000 human cell equivalents) and enables highly- sensitive and simultaneous detection of single nucleotide variants, small insertions / deletions, and CpG methylation comparable to the current state-of-the-art. We further combine SMRT-Tag with in situ adenine methyltransferase footprinting of nuclei (SAMOSA-Tag) to facilitate joint analysis of nucleosome repeat length, CTCF occupancy, and CpG methylation on individual chromatin fibers in osteosarcoma cells. SMRT-Tag promises to enable basic and clinical research by offering scalable, sensitive, and multimodal single-molecule genomic and epigenomic analyses in rare cell populations.
Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export
Authors: Qiao Yulong , Sun Qiang , Chen Xiaona , Wang Di , Su Ruibao , Xue Yuanchao , Sun Hao , Wang Huating
Published: August 2022

Skeletal muscle stem cells (also known as satellite cells, SCs) are essential for muscle regeneration and the regenerative activities of SCs are intrinsically governed by gene regulatory mechanisms but the post-transcriptional regulation in SCs remains largely unknown. N(6)-methyladenosine (m6A) modification of RNAs is the most pervasive and highly conserved RNA modification in eukaryotic cells and exerts powerful impact on almost all aspects of mRNA processing which is mainly endowed by its binding with m6A reader proteins. Here in this study, we investigate the previously uncharacterized regulatory roles of YTHDC1, a m6A reader in SCs. Our results demonstrate YTHDC1 is an essential regulator of SC activation and proliferation upon acute injury induced muscle regeneration. The induction of YTHDC1 is indispensable for SC activation and proliferation thus inducible YTHDC1 depletion almost abolishes SC regenerative capacity. Mechanistically, transcriptome-wide profiling using LACE-seq in both SCs and C2C12 myoblasts identifies m6A mediated binding targets of YTHDC1. Next, splicing analysis defines splicing mRNA targets of m6A-YTHDC1. Furthermore, nuclear export analysis also leads to identification of potential mRNA export targets of m6A-YTHDC1 in SCs and C2C12 myoblasts and interestingly some mRNAs can be regulated at both splicing and export levels. Lastly, we map YTHDC1 interacting protein partners in myoblasts and unveil a myriad of factors governing mRNA splicing, nuclear export and transcription, among which hnRNPG appears to be a bona fide interacting partner of YTHDC1. Altogether, our findings uncover YTHDC1 as an essential factor controlling SC regenerative ability through multi-faceted gene regulatory mechanisms in myoblast cells.
Pink1-mediated mitophagy in the endothelium releases proteins encoded by mitochondrial DNA and activates neutrophil responses
Authors: Gajwani Priyanka , Wang Li , Srivastava Shubhi , Ye Zijing , Kim Young-Mee , Krantz Sarah , Wang Dong-Mei , Tiruppathi Chinnaswamy , Toth Peter T. , Rehman Jalees
Published: August 2022

Given their ancient evolutionary origins, eukaryotic mitochondria possess multiple vestiges of their prokaryotic ancestors. One such factor is the N-terminal formylation of proteins encoded by mitochondrial DNA. N-formylated proteins are also released by bacteria and trigger activation of immune cells such as neutrophils. Growing evidence indicate that circulating levels of mitochondrial formyl proteins are elevated in the serum of patients with excessive inflammatory responses and trigger neutrophil activation like their bacterial counterparts. However, the cellular source of these proteins, and the mechanism by which they are released into the circulation is not known. In this study, we have identified vascular endothelial cells as a source of mitophagy induced release of formyl proteins in response to inflammatory mediators in vitro. Mechanistically, endothelial mitophagy required activation of the Pink1 pathway. Using liposomal delivery of sgRNA targeting Pink1 in mice expressing endothelial-specific Cas9, we developed a mouse model in which Pink1 is specifically depleted in the endothelium. Deletion of endothelial Pink1 was remarkably protective in endotoxin-induced lung inflammation, resulting in reduced neutrophil infiltration and significantly reduced death in mice. We thus propose that endothelial cells upregulate pro-inflammatory mitophagy in response to inflammation, leading to release of mitochondrial formyl peptides and detrimental neutrophil recruitment into the lung.
Isoform-specific Disruption of the TP73 Gene Reveals a Critical Role for TAp73gamma in Tumorigenesis via Leptin
Authors: Kong Xiangmudong , Yan Wensheng , Sun Wenqiang , Zhang Yanhong , Yang Hee Jung , Chen Mingyi , Chen Hongwu , de Vere White Ralph W. , Zhang Jin , Chen Xinbin
Published: August 2022

TP73, a member of the p53 family, is expressed as TAp73 and ΔNp73 along with multiple C-terminal isoforms (α−η). ΔNp73 is primarily expressed in neuronal cells and necessary for neuronal development. Interestingly, while TAp73α is a tumor suppressor and predominantly expressed in normal cells, TAp73 is found to be frequently altered in human cancers, suggesting a role of TAp73 C-terminal isoforms in tumorigenesis. To test this, the TCGA SpliceSeq database was searched and showed that exon 11 (E11) exclusion occurs frequently in several human cancers. We also found that p73α to p73γ isoform switch resulting from E11 skipping occurs frequently in human prostate cancers and dog lymphomas. To determine whether p73α to p73γ isoform switch plays a role in tumorigenesis, CRISPR technology was used to generate multiple cancer cell lines and a mouse model in that Trp73 E11 is deleted. Surprisingly, we found that in E11-deificient cells, p73γ becomes the predominant isoform and exerts oncogenic activities by promoting cell proliferation and migration. In line with this, E11-deficient mice were more prone to obesity and B-cell lymphomas, indicating a unique role of p73γ in lipid metabolism and tumorigenesis. Additionally, we found that E11-deficient mice phenocopies Trp73-deficient mice with short lifespan, infertility, and chronic inflammation. Mechanistically, Mechanistically, we showed that Leptin, a pleiotropic adipocytokine involved in energy metabolism and oncogenesis, was highly induced by p73γ, necessary for p73γ-mediated oncogenic activity, and associated with p73α to γ isoform switch in human prostate cancer and dog lymphoma. Finally, we showed that E11-knockout promoted, whereas knockdown of p73γ or Leptin suppressed, xenograft growth in mice. Our study indicates that the p73γ-Leptin pathway promotes tumorigenesis and alters lipid metabolism, which may be targeted for cancer management.
Robin’s Viewer: Using Deep-Learning Predictions to Assist EEG Annotation
Authors: Weiler Robin , Diachenko Marina , Juarez-Martinez Erika , Avramiea Arthur-Ervin , Bloem Peter , Linkenkaer-Hansen Klaus
Published: August 2022

Machine learning techniques such as deep learning have been increasingly used to assist EEG annotation, by automating artifact recognition, sleep staging, and seizure detection. In lack of automation, the annotation process is prone to bias, even for trained annotators. On the other hand, completely automated processes do not offer the users the opportunity to inspect the models’ output and re-evaluate potential false predictions. As a first step towards addressing these challenges, we developed Robin’s Viewer (RV), a Python-based EEG viewer for annotating time-series EEG data. The key feature distinguishing RV from existing EEG viewers is the visualization of output predictions of deep-learning models trained to recognize patterns in EEG data. RV was developed on top of the plotting library Plotly, the app-building framework Dash, and the popular M/EEG analysis toolbox MNE. It is an open-source, platform-independent, interactive web application, which supports common EEG-file formats to facilitate easy integration with other EEG toolboxes. RV includes common features of other EEG viewers, e.g., a view-slider, tools for marking bad channels and transient artifacts, and customizable preprocessing. Altogether, RV is an EEG viewer that combines the predictive power of deep-learning models and the knowledge of scientists and clinicians to optimize EEG annotation. With the training of new deep-learning models, RV could be developed to detect clinical patterns other than artifacts, for example sleep stages and EEG abnormalities.
Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors
Authors: Moghadasi Seyed Arad , Heilmann Emmanuel , Khalil Ahmed Magdy , Nnabuife Christina , Kearns Fiona L. , Ye Chengjin , Moraes Sofia N. , Costacurta Francesco , Esler Morgan A. , Aihara Hideki , Laer Dorothee von , Martinez-Sobrido Luis , Palzkill Timothy , Amaro Rommie E. , Harris Reuben S.
Published: August 2022

Vaccines and drugs have helped reduce disease severity and blunt the spread of SARS-CoV-2. However, ongoing virus transmission, continuous evolution, and increasing selective pressures have the potential to yield viral variants capable of resisting these interventions. Here, we investigate the susceptibility of natural variants of the main protease (Mpro/3CLpro) of SARS-CoV-2 to protease inhibitors. Multiple single amino acid changes in Mproconfer resistance to nirmatrelvir (the active component of Paxlovid). An additional clinical-stage inhibitor, ensitrelvir (Xocova), shows a different resistance mutation profile. Importantly, phylogenetic analyses indicate that several of these resistant variants have pre-existed the introduction of these drugs into the human population and are capable of spreading. These results encourage the monitoring of resistance variants and the development of additional protease inhibitors and other antiviral drugs with different mechanisms of action and resistance profiles for combinatorial therapy.

One Sentence Summary

Resistance to protease inhibitor drugs, nirmatrelvir (Paxlovid) and ensitrelvir (Xocova), exists in SARS-CoV-2 variants in the human population.
No Free Lunch from Deep Learning in Neuroscience: A Case Study through Models of the Entorhinal-Hippocampal Circuit
Authors: Schaeffer Rylan , Khona Mikail , Fiete Ila Rani
Published: August 2022

Research in Neuroscience, as in many scientific disciplines, is undergoing a renaissance based on deep learning. Unique to Neuroscience, deep learning models can be used not only as a tool but interpreted as models of the brain. The central claims of recent deep learning-based models of brain circuits are that they make novel predictions about neural phenomena or shed light on the fundamental functions being optimized. We show, through the case-study of grid cells in the entorhinal-hippocampal circuit, that one may get neither. We begin by reviewing the principles of grid cell mechanism and function obtained from first-principles modeling efforts, then rigorously examine the claims of deep learning models of grid cells. Using large-scale architectural and hyperparameter sweeps and theory-driven experimentation, we demonstrate that the results of such models may be more strongly driven by particular, non-fundamental, and post-hoc implementation choices than fundamental truths about neural circuits or the loss function(s) they might optimize. We discuss why these models cannot be expected to produce accurate models of the brain without the addition of substantial amounts of inductive bias, an informal No Free Lunch result for Neuroscience. Based on first principles work, we provide hypotheses for what additional loss functions will produce grid cells more robustly. In conclusion, circumspection and transparency, together with biological knowledge, are warranted in building and interpreting deep learning models in Neuroscience.
Can Artificial Intelligence Detect Monkeypox from Digital Skin Images?
Authors: Islam Towhidul , Hussain M.A. , Chowdhury Forhad Uddin Hasan , Islam B.M. Riazul
Published: August 2022

An outbreak of Monkeypox has been reported in 75 countries so far, and it is spreading at a fast pace around the world. The clinical attributes of Monkeypox resemble those of Smallpox, while skin lesions and rashes of Monkeypox often resemble those of other poxes, for example, Chickenpox and Cowpox. These similarities make Monkeypox detection challenging for healthcare professionals by examining the visual appearance of lesions and rashes. Additionally, there is a knowledge gap among healthcare professionals due to the rarity of Monkeypox before the current outbreak. Motivated by the success of artificial intelligence (AI) in COVID-19 detection, the scientific community has shown an increasing interest in using AI in Monkeypox detection from digital skin images. However, the lack of Monkeypox skin image data has been the bottleneck of using AI in Monkeypox detection. Therefore, in this paper, we used a web-scrapping-based Monkeypox, Chickenpox, Smallpox, Cowpox, Measles, and healthy skin image dataset to study the feasibility of using state-of-the-art AI deep models on skin images for Monkeypox detection. Our study found that deep AI models have great potential in the detection of Monkeypox from digital skin images (precision of 85%). However, achieving a more robust detection power requires larger training samples to train those deep models.
Innovation beyond the pandemic: the powerful potential of digital principal leadership
Authors: Sterrett William L. , Richardson Jayson W.
Published: August 2022

Purpose

This article presents findings from a recent study that examined award-winning digital principals. Findings are summarized with regard to the preparation and practice of school administrators.

Design/methodology/approach

The participants in the research study were 12 U.S. principals recognized for their digital principal leadership. The researchers interviewed the leaders to better understand the challenges and opportunities of being an innovative principal.

Findings

Digital principals engage their teachers in professional development in a differentiated manner rather than a ‘one size fits all’ approach. They are resourceful advocates for infrastructure upgrades and curriculum change. They are actively involved in professional networks that extend beyond their school walls. These principals empower teachers as leaders within and outside of their school. Finally, they helped tell the story of their school culture in unique ways.

Originality/value

With the onset of the pandemic, principal leadership has changed. Organizations can learn from innovative principals in this work and incorporate it into their preparation, professional development, and evaluation practices. School building leaders must emerge from the pandemic equipped to proactively lead the new normal of technology-savvy leadership opportunities.
The integration of logistics and marketing practice into baseline supply chain practices in the emerging markets
Authors: Dadzie Kofi , Dadzie Charlene , Johnston Wesley J. , Winston Evelyn , Wang Haizhong
Published: August 2022

Purpose

This study aims to draw on the strategy–structure–performance framework to investigate baseline supply chain (BSC) practices as a function of how firms structure logistics and marketing mix activities to achieve market share in the emerging market (EM) supply chain ecosystems.

Design/methodology/approach

The authors validate the study’s conceptual framework with survey data collected in two contrasting EM supply chain ecosystems. They include supply chains in EM economies with an advanced logistics/distribution infrastructure such as China and those in economies with poor logistics/distribution infrastructure such as Ghana. The authors use ordinary least squares regression and structural equation modeling analysis to examine the relative market share outcomes of different configurations of logistics-marketing practices (logistics-affordability marketing, logistics-accessibility marketing, logistics-acceptability marketing, logistics-and awareness and full integration into BSC).

Findings

Key findings confirm that the integration of logistics with marketing activities into BSC practice is more pervasive in EMs with high logistics performance index, such as China than in firms in EMs with low logistics performance index, such as Ghana. Moreover, the authors confirm that integrating logistics and marketing into BSC generates higher market share performance than logistics- or marketing-only practices in China and Ghana. These differences are driven more by the firm’s strategic orientation than the demands of competitive market conditions.

Research limitations/implications

The study focuses on BSC integration activities in the logistics and marketing functions because researchers have not updated this issue for the past two decades.

Practical implications

The study results provide managers with much-needed empirical evidence of the strategic benefit of BSC integration under different supply chain ecosystems in the EMs.

Originality/value

Linking BSC activities in logistics management and marketing management mix activities within the 4As marketing mix framework provides evidence to support the argument that the 4As marketing mix is an appropriate planning framework for EMs’ unique ecosystems.
Sustainability management and the success of international development projects: the role of political and social skills
Authors: Sawadogo Dieudonné , Sané Seydou , Kaboré Somnoma Edouard
Published: August 2022

Purpose

The objectives of this study are twofold: first, to identify the effect of sustainability management on the success of international development projects, and second, to investigate the moderating role of political and social skills on this relationship.

Design/methodology/approach

This study adopted a quantitative research methodology based on questionnaire data collected from 43 international development project managers from various fields in Burkina Faso (West Africa). Descriptive statistics and exploratory and confirmatory analyses using principal component analysis were used to assess the quality of the measurement model. A multiple regression analysis based on the partial least squares approach was used to test the hypotheses.

Findings

The results show that sustainability management positively contributes to the success of international development projects. However, given the specificities of these projects and their perception of success, the project coordinator's political and social skills do not predict a greater impact of sustainability management on the success of international development projects. The study also found that project coordinators prioritize their technical skills over behavioral ones.

Originality/value

This study fills a gap in the literature, given that little is known about the moderating role of political and social skills in the effect of sustainability management on the success of specific projects such as international development projects.
Impacts of game attractiveness and color of message on sport viewers' attention to prosocial message: an eye-tracking study
Authors: (Abdolreza) Oboudi Behnam , Elahi Alireza , Akbari Yazdi Hossein , Pyun Do Young
Published: August 2022

Purpose

In recent years, neurophysiological tools have been vastly applied in sport marketing research. Eye tracking, a pervasive sensor technology, has received a growing interest to examine the effects of advertising through sport on viewer attention. While there is a plethora of evidence in advertising that supports the positive effects of various advertising types and locations on viewer attention in various sport contexts, little is known about the role of a prosocial overlay ad on viewer attention when watching televised football matches. Therefore, this research aims to examine the differences in viewers' attention (i.e. fixation and duration) with regard to game attractiveness and colors of the prosocial message during televised football matches.

Design/methodology/approach

To identify the research gap, the authors first reviewed the relevant sport marketing and neuroscience research on advertising effectiveness. The authors selected a prosocial message displayed. Adopting an experimental research design and using eye tracking, this study examined the impacts of game attractiveness and colors of message on viewer attention to the prosocial message displayed on an overlay advertisement during a football match.

Findings

The authors found that the colors of prosocial messages and game attractiveness had significant effects on viewer attention to the prosocial message.

Originality/value

In this study, the authors sought to add advertisement color, as well as game attractiveness, to the extant knowledge in marketing literature as effective advertising factors in capturing viewers' attention. These variables can offer marketers new insights in designing effective advertisements for the context of televised sports events in a specialized field.
Timing and duration of drought modulate tree growth response in pure and mixed stands of Scots pine and Norway spruce
Authors: Aldea Jorge , Ruiz‐Peinado Ricardo , del Río Miren , Pretzsch Hans , Heym Michael , Brazaitis Gediminas , Jansons Aris , Metslaid Marek , Barbeito Ignacio , Bielak Kamil , Hylen Gro , Holm Stig‐Olof , Nothdurft Arne , Sitko Roman , Löf Magnus
Published: August 2022

Climate change is increasing the severity and frequency of droughts around the globe, leading to tree mortality that reduces production and provision of other ecosystem services. Recent studies show that growth of mixed stands may be more resilient to drought than pure stands. The two most economically important and widely distributed tree species in Europe are Norway spruce (Picea abies (L.) Karst) and Scots pine (Pinus sylvestris L.), but little is known about their susceptibility to drought when coexist.

This paper analyses the resilience (resistance, recovery rate and recovery time) at individual‐tree level using a network of tree‐ring collections from 22 sites along a climatic gradient from central Europe to Scandinavia. We aimed to identify differences in growth following drought between the two species and between mixed and pure stands, and how environmental variables (climate, topography and site location) and tree characteristics influence them.

We found that both the timing and duration of drought drive the different responses between species and compositions. Norway spruce showed higher vulnerability to summer drought, with both lower resistance and a longer recovery time than Scots pine. Mixtures provided higher drought resistance for both species compared to pure stands, but the benefit decreases with the duration of the drought. Especially climate sensitive and old trees in climatically marginal sites were more affected by drought stress.

Synthesis. Promoting Scots pine and mixed forests is a promising strategy for adapting European forests to climate change. However, if future droughts become longer, the advantage of mixed stands could disappear which would be especially negative for Norway spruce.
Medicalising the menace? The symbiotic convergence of medicine and law enforcement in the medicalisation of marijuana in Minnesota
Authors: Steel Ryan T.
Published: August 2022

The medicalisation of marijuana has occurred rapidly, albeit nonuniformly, across the US and around the world over the past 3 decades. This paper centres on the medicalisation of marijuana in Minnesota—which has one of the most restrictive programs in the country—as a case for evaluating the negotiation of institutional boundaries with the shift from criminalisation to medicalisation after nearly a century of criminal prohibition. Drawing upon Foucauldian discourse analyses of the medical and law enforcement associations’ position statements and legislative hearings that shaped medical marijuana policy in Minnesota, this paper demonstrates a symbiotic convergence between medicine and law enforcement through the deployment of shared discursive strategies in their opposition to medical marijuana that reinforce marijuana’s criminalised status by solidifying the boundaries between proper medicine and dangerous drugs. Criminal justice and medical institutions draw upon one another’s definitions, logics, and practices in a mutually constitutive manner, while still maintaining distinct user subjects and institutional interventions for each based on the user’s access to state‐approved forms of marijuana. The consequences for the governing of marijuana in Minnesota are explored, as well as the broader implications for the sociological study of medicalisation and criminalisation with respect to the governance of drugs and health.
Re-reading Kerschensteiner today: Doing VET in German vocational schools—A search for traces
Authors: Sloane Peter F E
Published: August 2022

Georg Kerschensteiner is often called the ‘father of the vocational school’ in Germany. Working in the context of the German Empire in the 19th century, his historical achievement was to design a concept of vocational education that dissolved the opposition between general education and vocational education that had existed since Humboldt. He combined this with the idea that work processes have a positive educational effect. He is, therefore, part of the ‘work-school’ movement as well. The educational-theoretical and didactic positions elaborated by Kerschensteiner were, in different eras, received approvingly and disapprovingly in German vocational education and training research. A history of the discourse of German vocational education has emerged in which the considerations raised by Kerschensteiner are recurrently addressed and sustained. This article attempts to trace Kerschensteiner's influence on educational practice through various historical contexts including the vocational schools in Germany today.