bluuebunny/crossref_metadata_2025 huggingface dataset:
Scientific support for nuclear medicine
Authors: Irwin Andy G.
Published: September 2023

This report was prepared on behalf of the British Nuclear Medicine Society (BNMS). Information included builds upon a previous BNMS report and also brings together information from a variety of sources to reflect current good scientific practice in this BNMS guidance. Training and career pathways are defined. Roles and functions provided by physicists are described, and the risks associated with inadequate scientific staffing are explored. Published staffing guidance has been reviewed and a recent publication on provision of Medical Physics Expert (MPE) support has been endorsed. The service models used in that publication have been populated with general physics support so that requirements for MPE and overall scientific provision may be assessed. In summary, this report is intended as a resource for those in a variety of roles including scientists considering a career in nuclear medicine and clinical scientists already practicing. It is also likely that some aspects of the document will be of interest to other clinical and medical professionals and to those involved in commissioning and managing nuclear medicine services.
A simplified general schema for rapid single time-point marrow predictive dosimetry
Authors: Kao Yung Hsiang
Published: September 2023

The red marrow is often the dose-limiting organ in systemic radionuclide therapy. However, multi-time-point personalised predictive dosimetry is resource intensive and impractical for routine clinical implementation. Single-time-point methods are a reasonable alternative for streamlining dosimetric workflows. However, there is a lack of single time-point methodology specific for the marrow. A simplified schema for rapid marrow predictive dosimetry is proposed based on direct image quantification of marrow radioconcentration, which may be generalised to most forms of systemic radionuclide therapy.
Maternal and birth outcomes in pregnant people with and without HIV in the Western Cape, South Africa
Authors: Slogrove Amy L. , Bovu Andisiwe , de Beer Shani , Phelanyane Florence , Williams Paige L. , Heekes Alexa , Kalk Emma , Mehta Ushma , Theron Gerhard , Abrams Elaine J. , Cotton Mark F. , Myer Landon , Davies Mary-Ann , Boulle Andrew
Published: September 2023

Introduction:

We evaluated associations of HIV and antiretroviral therapy (ART) with birth and maternal outcomes at a province-wide-level in the Western Cape, South Africa, in a recent cohort before dolutegravir-based first-line ART implementation.

Methods:

This retrospective cohort study included pregnant people delivering in 2018-2019 with data in the Western Cape Provincial Health Data Centre which integrates individual-level data on all public sector patients from multiple electronic platforms using unique identifiers. Adverse birth outcomes (stillbirth, low birth weight (LBW), very LBW (VLBW)) and maternal outcomes (early and late pregnancy-related deaths, early and late hospitalizations) were compared by HIV/ART status and adjusted prevalence ratios (aPRs) calculated using log-binomial regression.

Results:

Overall 171,960 pregnant people and their singleton newborns were included, 19% (N = 32 015) identified with HIV. Amongst pregnant people with HIV (PPHIV), 60% (N = 19 157) were on ART preconception, 29% (N = 9276) initiated ART during pregnancy and 11% (N = 3582) had no ART. Adjusted for maternal age, multiparity, hypertensive disorders and residential district, stillbirths were higher only for PPHIV not on ART [aPR 1.31 (95%CI 1.04–1.66)] compared to those without HIV. However, LBW and VLBW were higher among all PPHIV, with aPRs of 1.11–1.22 for LBW and 1.14–1.54 for VLBW. Pregnancy-initiated ART was associated with early pregnancy-related death (aPR 3.21; 95%CI 1.55–6.65), and HIV with or without ART was associated with late pregnancy-related death (aPRs 7.89–9.01).

Conclusions:

Even in the universal ART era, PPHIV experienced higher rates of LBW and VLBW newborns, and higher late pregnancy-related death regardless of ART status than pregnant people without HIV.
Magnetic Resonance Water Tracer Imaging Using 17O-Labeled Water
Authors: Kameda Hiroyuki , Kinota Naoya , Kato Daisuke , Fujii Takaaki , Harada Taisuke , Komaki Yuji , Sugimori Hiroyuki , Onodera Tomohiro , Tomiyasu Moyoko , Obata Takayuki , Kudo Kohsuke
Published: September 2023

Magnetic resonance imaging (MRI) is a crucial imaging technique for visualizing water in living organisms. Besides proton MRI, which is widely available and enables direct visualization of intrinsic water distribution and dynamics in various environments, MR-WTI (MR water tracer imaging) using 17O-labeled water has been developed, benefiting from the many advancements in MRI software and hardware that have substantially improved the signal-to-noise ratio and made possible faster imaging. This cutting-edge technique allows the generation of novel and valuable images for clinical use. This review elucidates the studies related to MRI water tracer techniques centered around 17O-labeled water, explaining the fundamental principles of imaging and providing clinical application examples. Anticipating continued progress in studies involving isotope-labeled water, this review is expected to contribute to elucidating the pathophysiology of various diseases related to water dynamics abnormalities and establishing novel imaging diagnostic methods for associated diseases.
Contemporary management of acute pancreatitis: What you need to know
Authors: Palumbo Rachael , Schuster Kevin M.
Published: September 2023

Acute pancreatitis and management of its complications is a common consult for the acute care surgeon. With the ongoing development of both operative and endoscopic treatment modalities, management recommendations continue to evolve. We describe the current diagnostic and treatment guidelines for acute pancreatitis through the lens of acute care surgery. Topics, including optimal nutrition, timing of cholecystectomy in gallstone pancreatitis, and the management of peripancreatic fluid collections, are discussed. Although the management severe acute pancreatitis can include advanced interventional modalities including endoscopic, percutaneous, and surgical debridement, the initial management of acute pancreatitis includes fluid resuscitation, early enteral nutrition, and close monitoring with consideration of cross-sectional imaging and antibiotics in the setting of suspected superimposed infection. Several scoring systems including the Revised Atlanta Criteria, the Bedside Index for Severity in Acute Pancreatitis score, and the American Association for the Surgery of Trauma grade have been devised to classify and predict the development of the severe acute pancreatitis. In biliary pancreatitis, cholecystectomy prior to discharge is recommended in mild disease and within 8 weeks of necrotizing pancreatitis, while early peripancreatic fluid collections should be managed without intervention. Underlying infection or ongoing symptoms warrant delayed intervention with technique selection dependent on local expertise, anatomic location of the fluid collection, and the specific clinical scenario. Landmark trials have shifted therapy from maximally invasive necrosectomy to more minimally invasive step-up approaches. The acute care surgeon should maintain a skill set that includes these minimally invasive techniques to successfully manage these patients. Overall, the management of acute pancreatitis for the acute care surgeon requires a strong understanding of both the clinical decisions and the options for intervention should this be necessary.
A novel risk variant block across introns 36–45 of CACNA1C for schizophrenia: a cohort-wise replication and cerebral region-wide validation study
Authors: Guo Xiaoyun , Wang Shibin , Lin Xiandong , Wang Zuxing , Dou Yikai , Cao Yuping , Zhang Yong , Luo Xinqun , Kang Longli , Yu Ting , Wang Zhiren , Tan Yunlong , Gao Shenshen , Zheng Hangxiao , Zhao Fen , Wang Huifen , Wang Kesheng , Xie Fan , Chen Wenzhong , Luo Xinguang
Published: September 2023

Objectives

Numerous genome-wide association studies have identified CACNA1C as one of the top risk genes for schizophrenia. As a necessary post-genome-wide association study (GWAS) follow-up, here, we focused on this risk gene, carefully investigated its novel risk variants for schizophrenia, and explored their potential functions.

Methods

We analyzed four independent samples (including three European and one African-American) comprising 5648 cases and 6936 healthy subjects to identify replicable single nucleotide polymorphism-schizophrenia associations. The potential regulatory effects of schizophrenia-risk alleles on CACNA1C mRNA expression in 16 brain regions (n = 348), gray matter volumes (GMVs) of five subcortical structures (n = 34 431), and surface areas and thickness of 34 cortical regions (n = 36 936) were also examined.

Results

A novel 17-variant block across introns 36–45 of CACNA1C was significantly associated with schizophrenia in the same effect direction across at least two independent samples (1.8 × 10−4 ≤ P ≤ 0.049). Most risk variants within this block showed significant associations with CACNA1C mRNA expression (1.6 × 10−3 ≤ P ≤ 0.050), GMVs of subcortical structures (0.016 ≤ P ≤ 0.048), cortical surface areas (0.010 ≤ P ≤ 0.050), and thickness (0.004 ≤ P ≤ 0.050) in multiple brain regions.

Conclusion

We have identified a novel and functional risk variant block at CACNA1C for schizophrenia, providing further evidence for the important role of this gene in the pathogenesis of schizophrenia.
Case of twin achondroplasia and autism coexistence and literature review
Authors: Bilgeç Nagehan , Balasar Özgür , Uzun Necati , Pekcan Sevgi , Bedel Fayize Maden , Çaksen Hüseyin
Published: September 2023

Achondroplasia and autism spectrum disorder (ASD) are two genetically based disorders. The coexistence of autism with chromosomal abnormalities such as Down syndrome, monogenic syndromes such as tuberous sclerosis, Fragile X, and Rett syndrome, and microdeletion syndromes such as Phelan-McDermid syndrome helps to shed light on the genetic basis of autism spectrum disorder. The association between ASD and achondroplasia has been reported twice in the literature. In this article, we report Turkish patients who were born as identical twins from IVF pregnancy of 34 and 36-year-old parents, clinically and molecularly diagnosed with achondroplasia, and diagnosed with ASD at the age of 39 months. Our case is the first twin patient with the coexistence of achondroplasia and autism. We discuss environmental and genetic factors contributing to the development of ASD.
Socio-economic predictors of Inuit hunting choices and their implications for climate change adaptation
Authors: Hillemann Friederike , Beheim Bret A. , Ready Elspeth
Published: September 2023

In the Arctic, seasonal variation in the accessibility of the land, sea ice and open waters influences which resources can be harvested safely and efficiently. Climate stressors are also increasingly affecting access to subsistence resources. Within Inuit communities, people differ in their involvement with subsistence activities, but little is known about how engagement in the cash economy (time and money available) and other socio-economic factors shape the food production choices of Inuit harvesters, and their ability to adapt to rapid ecological change. We analyse 281 foraging trips involving 23 Inuit harvesters from Kangiqsujuaq, Nunavik, Canada using a Bayesian approach modelling both patch choice and within-patch success. Gender and income predict Inuit harvest strategies: while men, especially men from low-income households, often visit patches with a relatively low success probability, women and high-income hunters generally have a higher propensity to choose low-risk patches. Inland hunting, marine hunting and fishing differ in the required equipment and effort, and hunters may have to shift their subsistence activities if certain patches become less profitable or less safe owing to high costs of transportation or climate change (e.g. navigate larger areas inland instead of targeting seals on the sea ice). Our finding that household income predicts patch choice suggests that the capacity to maintain access to country foods depends on engagement with the cash economy.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Small-scale farmer responses to the double exposure of climate change and market integration
Authors: Kramer K. L. , Hackman J. V.
Published: September 2023

Anthropologists have long studied how small-scale societies manage climate variation. Here, we investigate how Yucatec Maya subsistence farmers respond to climate stress, and the ways in which market integration may enhance or disturb response stategies. Using information on harvest returns, climate perceptions, household economics and helping networks, modelling results show that as farmers rely more on market inputs (e.g. seed, tractors, fertilizer) for a successful yield, the reasons given for a bad harvest shift from climate variables to access to quality inputs. We also find that social and economic diversification is key to mediating a household's experience of climate and market shocks. The Maya are astute stewards of climate knowledge, and have effective social and economic means to mitigate potential fluctuations in food availability. In the transition from a subsistence to a market integrated economy, these traditional strategies become strained. Reliance on market inputs forges a more rigid food production system that conflicts with the diversity and flexibility on which traditional strategies depend to manage climate variation. Moving forward, the best policies would be those that facilitate maintaining an equal footing in both a subsistence maize economy, while incorporating new market opportunities.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Antibacterial activity of menadione alone and in combination with oxacillin against methicillin-resistant Staphylococcus aureus and its impact on biofilms
Authors: Leitão Amanda Cavalcante , Ferreira Thais Lima , Gurgel do Amaral Valente Sá Lívia , Rodrigues Daniel Sampaio , de Souza Beatriz Oliveira , Barbosa Amanda Dias , Moreira Lara Elloyse Almeida , de Andrade Neto João Batista , Cabral Vitória Pessoa de Farias , Rios Maria Erivanda França , Cavalcanti Bruno Coêlho , Silva Jacilene , Marinho Emmanuel Silva , dos Santos Hélcio Silva , de Moraes Manoel Odorico , Júnior Hélio Vitoriano Nobre , da Silva Cecília Rocha
Published: September 2023

Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant

Staphylococcus aureus

(MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents.

Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant

S. aureus

strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress.

Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis.

Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant

S. aureus

strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity.

Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml−1, with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects.

Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of

S. aureus

infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.
Modeling the impact of genotype, age, sex, and continuous navigation on pathway integration performance
Authors: Pink Dorothea , Ilkel Ekin , Chandreswaran Varnan , Moser Dirk , Getzmann Stephan , Patrick Gajewski , Axmacher Nikolai , Zhang Hui
Published: September 2023

The Path Integration (PI) task stands as a fundamental activity within spatial navigation, encompassing a multifaceted underlying process that requires extensive computation of both translational and directional information during navigation. This task is postulated to engage the entorhinal cortex (EC), a critical brain region. Although rodent studies have firmly linked the EC with the PI task, such a correlation has yet to be definitively established in humans. Individuals harboring high-risk genes associated with Alzheimer’s disease (AD) present a unique opportunity to explore PI task performance in humans because EC is the first targeted region during the pathological development of AD. Furthermore, the execution of the PI task is also susceptible to the influences of age and gender. In order to methodically probe the influences of various factors on PI performance, we conducted a PI task in a cohort characterized by high-risk AD-associated genes in a virtual island environment with surrounding landmarks. Our findings unveiled intricate interactions between these risk genes, age, and gender in shaping PI performance, an influence primarily mediated through distance and angle estimation. This study provides an illuminating perspective on the investigation into the functional role of the entorhinal cortex within the context of the PI task.
Infectious touching: Has COVID-19 changed our perceptions of social touch? A neural and behavioral study
Authors: Zoabi Dana , Abado Elinor , Shamay-Tsoory Simone , Peled-Avron Leehe
Published: September 2023

Social touch is essential for reducing stress, improving mood and fostering a sense of social connectedness. Stimuli related to social touch are generally perceived as positive. Nevertheless, the social restrictions imposed by the COVID-19 pandemic may have changed the way human beings perceive and react to social touch. Indeed, the social distancing imposed by the pandemic may have had long term effects on human perceptions of social touch. In the current study, we examined how perceptions of interpersonal touch in social interactions were affected by the COVID-19 pandemic. Specifically, we compared behavioral and neural responses to observed social touch between two groups: pre- and post-COVID-19. Participants in both groups rated the pleasantness of photos of social touch between humans, nonsocial touch between inanimate objects or non-touch photos of either two humans or inanimate objects. We hypothesized that social touch in the post-COVID-19 group would induce hypervigilance due to the risk of infection. In line with our predictions, we found behavioral changes in perceptions of social touch among participants in this group, who rated photos with touch as less pleasant than did participants in the pre-COVID-19 group. Participants in the post-COVID-19 group also rated photos with humans as less pleasant than did participants in the pre-COVID-19 group. Additionally, EEG analysis revealed neural changes in the ERP components associated with hypervigilance: P1 and LPP. Contrary to pre-COVID-19 measures showing more positive P1 amplitudes for touch than for non-touch photos, after COVID-19 no differences in P1 amplitudes were found between touch and non-touch photos. Furthermore, after COVID-19 the P1 amplitudes for human and inanimate photos in the touch condition were similar, a pattern that did not emerge prior to COVID-19. These findings suggest that COVID-19 had a surprising impact on human perceptions of social touch, such that observing nonsocial touch evoked more positive emotions than observing human touch. Further, these findings may reflect shifts in attention or changes in the salience of touch-related information due to the altered circumstances brought about by the pandemic. Overall, our results indicate that COVID-19 has modified human perceptions of social touch, providing evidence that the pandemic has affected individuals’ perceptual and evaluative processes and highlighting the importance of considering social and environmental factors in understanding subjective experiences.
Exploring associations between the teat apex metagenome andStaphylococcus aureusintramammary infection risk in primiparous cows under organic directives
Authors: Dean C. J. , Peña-Mosca F. , Ray T. , Wehri T. J. , Sharpe K. , Antunes A.M. , Doster E. , Fernandes L. , Calles V. F. , Bauman C. , Godden S. , Heins B. , Pinedo P. , Machado V. S. , Caixeta L. S. , Noyes N. R.
Published: September 2023

The primary objective of this study was to identify associations between teat apex microbiome andStaphylococcus aureusintramammary infection (IMI) risk in primiparous cows during the first 5 weeks after calving. We performed a case-control study using shotgun metagenomics of the teat apex and culture-based milk data collected longitudinally from 710 primiparous cows on 5 organic dairy farms. We observed a strong association betweenS. aureusDNA in the metagenomic teat apex data prior to parturition and the odds ofS. aureusIMI after parturition (OR = 38.9, 95% CI: 14.84-102.21). Differential abundance analysis confirmed this association, with cases having a 23.8 higher log fold change (LFC) in abundance ofS. aureusin their samples compared to controls. Of the most prevalent microorganisms in controls, those associated with a lower risk of post-calvingS. aureusIMI includedMicrobacteriumphage Min 1 (OR = 0.37, 95% CI: 0.25-0.53),Corynebacterium efficiens(OR = 0.53, 95% CI: 0.30-0.94),Kocuria polaris(OR = 0.54, 95% CI: 0.35-0.82),Micrococcus terreus(OR = 0.64, 95% CI: 0.44-0.93) andDietzia alimentaria(OR = 0.45, 95% CI: 0.26-0.75). Microcin B17 was the most prevalent antibacterial peptide on the teat apex of cases and controls (99.7% in both groups). The predicted abundance of Microcin B17 was also higher in cases compared to controls (LFC 0.26). Cow and farm random effects often explained a large proportion of the observed variability in the teat apex microbiome, suggesting that our results need to be interpreted within the context of the random effects.

IMPORTANCE

Intramammary infections (IMI) caused byStaphylococcus aureusremain an important problem for the organic dairy industry. The microbiome on the external skin of the teat apex may play a role in mitigatingS. aureusIMI risk, in particular the production of antimicrobial peptides (AMPs) by commensal microbes. However, current studies of the teat apex microbiome utilize a 16S approach, which precludes detection of genomics features such as AMPs. Therefore, further research using a shotgun metagenomic approach is needed to understand what role pre-partum teat apex microbiome dynamics play in IMI risk.
An analysis of the onset and clinical characteristics in cystic lymphatic malformations
Authors: Hashizume Naoki , Fujino Akihiro , Takahashi Masataka , Furugane Ryoya , Kobayashi Tamotsu , Mori Teizaburo , Watanabe Eiichiro , Kano Motohiro , Yoneda Akihiro , Kanamori Yutaka
Published: September 2023

Background

This study aimed to investigate and compare the applied treatments and the prognosis between patients with congenital and acquired onset cystic lymphatic malformation (cLM).

Methods

This study was a retrospective cohort study in a single hospital. Patients with cLM treated at our institution were included in this study, and divided into those diagnosed in utero or at birth (CO) and those diagnosed later after birth (AO) with the acquired emerged lesion. Age, site, and size of the lesion, histological subtype, invasiveness grade of the treatment, and the treatment outcomes were compared.

Results

In total, 147 patients were included. The CO group (n = 85) received more invasive treatment, with the distribution of treatment grades differing significantly from the AO group (n = 62,p= 0.005). cLMs were mainly located on the neck (n = 53, 36.1%), followed by the head and face (n = 31, 21.1%), axilla (n = 7, 4.8%), chest wall (n = 18, 12.2%), mediastinum (n = 5, 3.4%), abdominal wall (n = 4, 2.7%), retroperitoneum (n = 4, 2.7%), hip (n = 5, 3.4%), arm and hand (n = 8, 5.4%), and leg and foot (n = 12, 8.2%). No significant between-group difference was found in terms of the distribution of the main lesions (p= 0.45).

Macrocystic LM was more frequent in the AO group, with a significantly different subtype ratio (p= 0.02). The frequency of lower-grade treatment was significantly higher in the macrocystic LM subtype in the AO group (p< 0.001), and this group had a significantly higher treatment completion rate (p= 0.004). During the treatment course, improvement was seen in 72.9% and 71.0% of patients in the CO group and the AO group, respectively, indicating no significant difference (p=0.79).

Conclusions

cLMs that newly appeared after birth tended to be macrocystic and had better outcomes with less-invasive treatment than congenital-onset cLMs. The timing of cLM onset could be a key prognostic factor.
The transcription factor Sfp1 imprints specific classes of mRNAs and links their synthesis to cytoplasmic decay
Authors: Kelbert M. , Jordán-Pla A. , de-Miguel-Jiménez L. , García-Martínez J. , Selitrennik M. , Guterman A. , Henig N , Granneman S. , Pérez-Ortín J.E. , Chávez S. , Choder M.
Published: September 2023

To function effectively as an integrated system, the transcriptional and post-transcriptional machineries must communicate through mechanisms that are still poorly understood. Here we focus on Sfp1, known to regulate transcription of proliferation-related genes. We show that Sfp1 can regulate transcription either by binding to promoters, like most known transcription activators, or by binding to the transcribed regions (gene bodies), probably via RNA polymerase II (Pol II). We further studied the first mode of Sfp1 activity and found that, following promoter binding, Sfp1 binds to gene bodies and affects Pol II configuration, manifested by dissociation or conformational change of its Rpb4 subunit and increased backtracking. Surprisingly, Sfp1 binds to a subset of mRNAs co-transcriptionally and stabilizes them. The interaction between Sfp1 and its client mRNAs is controlled by their respective promoters and coincides with Sfp1’s dissociation from chromatin. . Intriguingly, Sfp1 dissociation from the chromatin correlates with the extent of the backtracked Pol II. We propose that, following promoter recruitment, Sfp1 accompanies Pol II and regulates backtracking. The backtracked Pol II is more compatible with Sfp1’s relocation to the nascent transcripts, whereupon Sfp1 accompanies these mRNAs to the cytoplasm and regulates their stability. Thus, Sfp1’s co-transcriptional binding imprints the mRNA fate, serving as a paradigm for the cross-talk between the synthesis and decay of specific mRNAs. The interplay between Sfp1’s two modes of transcription regulation remains to be examined.
Increasing the Throughput and Reproducibility of Activity-Based Proteome Profiling Studies with Hyperplexing and Intelligent Data Acquisition
Authors: Budayeva Hanna G. , Ma Taylur P. , Wang Shuai , Choi Meena , Rose Christopher M.
Published: September 2023

Intelligent data acquisition (IDA) strategies, such as real-time database search (RTS), have improved the depth of proteome coverage for experiments that utilize isobaric labels and gas phase purification techniques (i.e., SPS-MS3). While most applications of IDA have been focused on the analysis of protein abundance, these approaches have recently been applied to activity-based proteome profiling (ABPP) studies aimed at characterization of protein site engagement by small molecules. In this work, we extend IDA capabilities offered by vendor software through a program called InSeqAPI. First, we demonstrate robust performance of InSeqAPI in the analysis of biotinylated cysteine peptides from ABPP experiments. Then, we describe PairQuant, a method within InSeqAPI designed for the hyperplexing approach that utilizes protein-level isotopic labeling and peptide-level TMT labeling. PairQuant allows for TMT analysis of 36 conditions in a single sample and achieves ∼98% coverage of both peptide pair partners in a hyperplexed experiment as well as a 40% improvement in the number of quantified cysteine sites compared to non-RTS acquisition. We applied this method in ABPP study of ligandable cysteine sites in the nucleus leading to an identification of additional druggable sites on protein-and DNA-interaction domains of transcription regulators and on nuclear ubiquitin ligases.
A Functional Exodermal Suberin is Key for Plant Nutrition and Growth in Potato
Authors: Company-Arumí Dolors , Montells Carlota , Iglesias Mònica , Marguí Eva , Verdaguer Dolors , Vogel-Mikus Katarina , Kelemen Mitja , Figueras Mercè , Anticó Enriqueta , Serra Olga
Published: September 2023

Angiosperm roots, except in Arabidopsis, have both endodermis and exodermis, which regulate radial water and solute movement through lignin and suberin deposition. While endodermal suberin in Arabidopsis acts as a barrier to water and solute uptake and backflow, its implications in other angiosperms with both layers and the role of exodermal suberin remain unclear. We examined potato roots (Solanum tuberosum) and found that exodermis lacks the typical Casparian strip but forms an outer lignin cap, and quickly suberizes near the root tip. In contrast, a few endodermal cells, with Casparian strip, start suberizing much later. The continuous early exodermal suberization covering the root underlines its potential role in mineral nutrient radial movement. To demonstrate it, we used plants downregulating the suberin biosynthetic geneCYP86A33, which had the root suberin reduced in a 61%. Phenotypic analyses of the suberin-deficient mutant showed altered mineral nutrient concentration, slightly reduced water content and compromised growth. Micro-PIXE analyses identified the distribution of elements within the roots and highlighted anatomical compartments defined by apoplastic barriers. These findings advance our understanding of nutrient radial transport, demonstrate exodermal suberin as a bidirectional and selective barrier to element movement, and underscore its importance in nutrient homeostasis and plant growth.
High-Throughput Short Sequence Typing Schemes forPseudomonas aeruginosaandStenotrophomonas maltophiliapure culture and environmental DNA
Authors: Bourdin Thibault , Benoit Marie-Ève , Bédard Emilie , Prévost Michèle , Quach Caroline , Déziel Eric , Constant Philippe
Published: September 2023

Molecular typing techniques are employed to determine the genetic similarities between bacterial isolates. These methods primarily utilize specific genetic markers or analyze the complete genome sequence of pure bacterial cultures. However, the use of environmental DNA profiling to assess epidemiologic links between patients and their environment has not been explored in depth. This work reports on the development and validation of two High-Throughput Short Sequence Typing (HiSST) schemes targeting the opportunistic pathogensPseudomonas aeruginosaandStenotrophomonas maltophilia, along with a modified SM2I medium for specific isolation ofS. maltophilia. Our HiSST schemes are based on four discriminative loci for each species and demonstrate high discrimination power, comparable to pairwise whole genomes comparison. Moreover, each scheme includes species-specific PCR primers, enabling precise differentiation from closely related taxa without the need for upstream culture-dependent methods. For example, the primers designed to target thebvgSlocus allow to distinguishP. aeruginosafrom the very closely relatedPseudomonas paraeruginosasp. nov. The selected loci included in the schemes forP. aeruginosa(pheT,btuB,sdaA,bvgS) and forS. maltophilia(yvoA,glnG,ribA,tycC), are within the range of 271 to 330 base pairs adapted to massive parallel amplicon sequencing technology. A R-based script implemented in the DADA2 pipeline was assembled to facilitate HiSST analysis for efficient and accurate genotyping ofP. aeruginosaandS. maltophilia. The performance of both schemes was demonstrated throughin-silicovalidations, assessments against reference culture collections, and a case study involving environmental samples.
Leishmania infantum-exploited Nrf2 transcription factor as a virulence process to escape macrophage-driven ferroptosis-like leishmanicidal process
Authors: Blot Clément , Coulson Kimberley , Salon Marie , Tertrais Margot , Planès Rémi , Santoni Karin , Authier Hélène , Jacquemin Godefroy , Rahabi Mouna , Parny Mélissa , Letron Isabelle Raymond , Meunier Etienne , Lefèvre Lise , Coste Agnès
Published: September 2023

Macrophages are the main effector cells duringLeishmaniainfection. They contribute to the detection and elimination ofLeishmania spp.and may also promote parasite resilience. Here, we report that the activation of the transcription factor Nrf2 in macrophages plays a pivotal role in the progression ofLeishmania infantuminfection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of NOX2/ROS axis in the early Nrf2 activation and subsequently of PGE2/EP2r signalling in the sustainment of Nrf2 activation uponL. infantuminfection. Moreover, we establish macrophage-driven ferroptosis-like process as a cell death program ofL. infantumand the protective effect of Nrf2 in macrophages againstL. infantumdeath. Altogether, these results identify Nrf2 as a critical factor for the susceptibility ofLeishmania infantuminfection, highlighting Nrf2 as a promising pharmacological target for the development of new therapeutic approaches for the treatment of visceral leishmaniasis.
Bibliometric analysis of emerging trends and research foci in brainstem tumor field over thirty years (1992-2023)
Authors: Geng Yibo , Xie Luyang , Li Jinping , Wang Yang , Li Xiong
Published: September 2023

Background

Over the past several decades, numerous articles have been published on brainstem tumors. However, there has been limited bibliometric analysis in this field. Therefore, we conducted a bibliometric analysis to elucidate the evolution and current status of brainstem tumor research.

Methods

We retrieved 5,927 studies published in English between 1992 and 2023 from the Web of Science Core Collection database. We employed bibliometric tools and VOSviewer to conduct the analysis.

Results

We identified and included a total of 5,927 publications for further analysis. The number of annual publications has exhibited steady growth over time. The United States accounted for the highest number of publications and total citations. The St. Jude Children’s Research Hospital emerged as the most productive institution, while the Journal of Neurosurgery was the leading journal in terms of publication output. Among individual researchers, Liwei Zhang had the highest number of publications, while Eric Bouffet received the most citations in this field. The study titled "Somatic Histone H3 Alterations in Pediatric Diffuse Intrinsic Pontine Gliomas and Non-brainstem Glioblastomas" stood out as the most cited work in this field. Keyword analysis revealed that immune therapy and epigenetic research are the focal points of this field.

Conclusion

Our bibliometric analysis underscores the enduring significance of brainstem tumors in the realm of neuro-oncology research. The field’s hotspots have transitioned from surgery and radiochemotherapy to investigating epigenetic mechanisms and immune therapy.
Biophysically Interpretable Inference of Cell Types from Multimodal Sequencing Data
Authors: Chari Tara , Gorin Gennady , Pachter Lior
Published: September 2023

Multimodal, single-cell genomics technologies enable simultaneous capture of multiple facets of DNA and RNA processing in the cell. This creates opportunities for transcriptome-wide, mechanistic studies of cellular processing in heterogeneous cell types, with applications ranging from inferring kinetic differences between cells, to the role of stochasticity in driving heterogeneity. However, current methods for determining cell types or ‘clusters’ present in multimodal data often rely on ad hoc or independent treatment of modalities, and assumptions ignoring inherent properties of the count data. To enable interpretable and consistent cell cluster determination from multimodal data, we present meK-Means (mechanistic K-Means) which integrates modalities and learns underlying, shared biophysical states through a unifying model of transcription. In particular, we demonstrate how meK-Means can be used to cluster cells from unspliced and spliced mRNA count modalities. By utilizing the causal, physical relationships underlying these modalities, we identify shared transcriptional kinetics across cells, which induce the observed gene expression profiles, and provide an alternative definition for ‘clusters’ through the governing parameters of cellular processes.
In vitroproliferation ofMytilus edulismale germ cell progenitors
Authors: Khorami Hajar Hosseini , Breton Sophie , Angers Annie
Published: September 2023

Our understanding of basic cellular processes has mostly been provided by mammalian cell culture, and by some non-mammalian vertebrate and few invertebrate cell culture models. Developing reliable culture conditions for non-model organisms is essential to allow investigation of more unusual cellular processes. Here, we investigate how cells isolated from different tissues of the marine musselMytilus edulisthrive and survivein vitroin the hope of establishing a suitable laboratory model for the investigation of cellular mechanisms specific to these bivalve mollusks. We found that cells dissociated from male mantle tissue attached to the culture vessels and proliferated wellin vitro, whereas all other cell types, although remaining viable, did not maintain divisions over three to four weeks in culture. We used antibodies against the germ-line marker DEAD-box helicase 4 (DDX4), also known as VASA, and the epithelial cell marker cytokeratin to distinguish different cell types in culture. DDX4-positive cells were the only cells that significantly proliferated in culture, and only from male tissue samples. Overall, the culture conditions described here allow an efficient selection of male germ cells that could be used to study specific cellular mechanismsin vitro.
Characterization of a family I inorganic pyrophosphatase from Legionella pneumophila Philadelphia 1
Authors: Moorefield Julia , Konuk Yagmur , Norman Jordan O. , Abendroth Jan , Edwards Thomas E. , Lorimer Donald D. , Mayclin Stephen J. , Staker Bart L. , Craig Justin K. , Barett Kayleigh F. , Barrett Lynn K. , Van Voorhis Wesley C. , Myler Peter J. , McLaughlin Krystle J.
Published: September 2023

Inorganic pyrophosphate (PPi) is generated as an intermediate or byproduct of many fundamental metabolic pathways, including DNA/RNA synthesis. The intracellular concentration of PPi must be regulated as buildup can inhibit many critical cellular processes. Inorganic pyrophosphatases (PPases) hydrolyze PPi into two orthophosphates (Pi), preventing the toxic accumulation of the PPi byproduct in cells and making Pi available for use in biosynthetic pathways. Here, the crystal structure of a family I inorganic pyrophosphatase from Legionella pneumophila is reported at 2.0 Å resolution. L. pneumophila PPase (LpPPase) adopts a homohexameric assembly and shares the oligonucleotide/oligosaccharide-binding (OB) β-barrel core fold common to many other bacterial family I PPases. LpPPase demonstrated hydrolytic activity against a general substrate, with Mg2+ being the preferred metal cofactor for catalysis. Legionnaires' disease is a severe respiratory infection caused primarily by L. pneumophila, and thus increased characterization of the L. pneumophila proteome is of interest.
Big data analytics adaptive prospects in sustainable manufacturing supply chain
Authors: Raj Rohit , Kumar Vimal , Shah Bhavin
Published: September 2023

Purpose

Despite the current progress in realizing how Big Data Analytics can considerably enhance the Sustainable Manufacturing Supply Chain (SMSC), there is a major gap in the storyline relating factors of Big Data operations in managing information and trust among several operations of SMSC. This study attempts to fill this gap by studying the key enablers of using Big Data in SMSC operations obtained from the internet of Things (IoT) devices, group behavior parameters, social networks and ecosystem framework.

Design/methodology/approach

Adaptive Prospects (Improving SC performance, combating counterfeits, Productivity, Transparency, Security and Safety, Asset Management and Communication) are the constructs that this research first conceptualizes, defines and then evaluates in studying Big Data Analytics based operations in SMSC considering best worst method (BWM) technique.

Findings

To begin, two situations are explored one with Big Data Analytics and the other without are addressed using empirical studies. Second, Big Data deployment in addressing MSC barriers and synergistic role in achieving the goals of SMSC is analyzed. The study identifies lesser encounters of barriers and higher benefits of big data analytics in the SMSC scenario.

Research limitations/implications

The research outcome revealed that to handle operations efficiently a 360-degree view of suppliers, distributors and logistics providers' information and trust is essential.

Practical implications

In the Post-COVID scenario, the supply chain practitioners may use the supply chain partner's data to develop resiliency and achieve sustainability.

Originality/value

The unique value that this study adds to the research is, it links the data, trust and sustainability aspects of the Manufacturing Supply Chain (MSC).
Tone and credibility in voluntary disclosures
Authors: Bodoff David , Hirsch Iris
Published: September 2023

Purpose

The purpose of this research paper is to study attitudinal responses to the tone of a voluntary disclosure. It is known that tone can affect market response. Existing literature assumes that investors' attitudes mediate these effects, but these attitudinal mediators have not been directly measured. The authors are especially interested in cases where a firm is reporting poor financial results. The purpose is to trace the mechanism and conditions under which tone affects the credibility of a voluntary disclosure.

Design/methodology/approach

The authors conducted a 2 × 2 between-subjects study that manipulates financial performance (good/bad) and tone (positive/negative). The attitudinal dependent variable is the credibility of the management discussion, with persuasive intent as a mediator of the effects of tone on credibility.

Findings

In the case of bad financial results, a positive tone has a negative effect on credibility as the authors predict. This effect is fully mediated by perceived “persuasive intent”. In the case of good financial performance, credibility is higher when management adopts a positive tone, even though there, too, subjects perceive the persuasive intent.

Research limitations/implications

The research paper establishes a bridge between the communications and finance literature on the effect of tone in voluntary disclosures. The empirical findings provide initial evidence and new detail regarding an attitudinal response (credibility) that the finance literature often assumes is responsible for mediating market responses to voluntary disclosures. One unexpected finding with interesting implications is that positive tone increases credibility in the case of good news. The implication is that a firm may indulge in taking a victory lap to celebrate good news, without harming the credibility of their corporate communications. Additional research is warranted that combines theory and methods from communications and finance, to further elaborate the attitudinal mechanisms behind the market effects of tone in voluntary disclosures.

Originality/value

At the most general level, the original contribution is the creation of a theoretical and methodological bridge between the communications and finance literature, regarding the effect of tone in voluntary disclosures. This research proposes an integrated theoretical framework, in which the concept of incentives shapes the relationships between the firm's financial situation, a disclosure's tone and its credibility. Methodologically, the authors employ an experimental method, which is more typical in the communications literature, to illuminate the attitudinal effects of tone that are frequently mentioned and assumed in the finance literature.
Looking at the darker side of the mirror: the impact of CEO's narcissism on corporate social irresponsibility
Authors: Riera Marta , Iborra María
Published: September 2023

Purpose

The aim of this article is to highlight the major part played by executives in the escalation of corporate social irresponsibility (CSI). Based on the upper echelons theory, the authors developed a model which shows the essential role of CEOs in explaining CSI. The authors proposed that the key personality traits of CEOs—narcissism—, as well as their power, could explain the degree of CSI.

Design/methodology/approach

Due to the significant methodological challenges when investigating CSI, the authors explored a novel method for measuring CSI in order to assess the degree of irresponsible behaviors. The authors build a CSI scale based on the perceptions of key informants, i.e. experts with diverse professional backgrounds. The authors apply CSI scale in a sample of 84 Spanish companies that were involved in CSI.

Findings

The results of the authors’ empirical study show the positive and significant influence of CEO narcissism and CEO power on the degree of CSI.

Research limitations/implications

On the one hand, corporate irresponsibility scandals have relevant social consequences and practical implications. On the other hand, narcissism is a natural feature of managers in top positions that is increasing in societies.

Practical implications

The authors’ findings may help CEOs, TMTs and corporate boards to acknowledge potential sources of CSI decreasing its likelihood through counterbalancing CEO's power and considering the dark side of narcissism.

Social implications

On the one hand, corporate scandals have relevant social and practical implications. On the other hand, narcissism is a natural feature of managers in top positions that is increasing in societies.

Originality/value

In this paper, the authors highlight the role of CEOs characteristics and their firms as the key actors for explaining and understanding the degree of CSI.