bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasmid-encoded lactose metabolism and mobilized colistin resistance (mcr-9) genes in Salmonella enterica serovars isolated from dairy facilities in the 1980s
Authors: Kröger Carsten , Lerminiaux Nicole A. , Ershova Anna S. , MacKenzie Keith D. , Kirzinger Morgan W. , Märtlbauer Erwin , Perry Benjamin J. , Cameron Andrew D. S. , Schauer Kristina
Published: November 2023

Horizontal gene transfer by plasmids can confer metabolic capabilities that expand a host cell’s niche. Yet, it is less understood whether the coalescence of specialized catabolic functions, antibiotic resistances and metal resistances on plasmids provides synergistic benefits. In this study, we report whole-genome assembly and phenotypic analysis of five

Salmonella enterica

strains isolated in the 1980s from milk powder in Munich, Germany. All strains exhibited the unusual phenotype of lactose-fermentation and encoded either of two variants of the lac operon. Surprisingly, all strains encoded the mobilized colistin resistance gene 9 (mcr-9), long before the first report of this gene in the literature. In two cases, the mcr-9 gene and the lac locus were linked within a large gene island that formed an IncHI2A-type plasmid in one strain but was chromosomally integrated in the other strain. In two other strains, the mcr-9 gene was found on a large IncHI1B/IncP-type plasmid, whereas the lac locus was encoded on a separate chromosomally integrated plasmidic island. The mcr-9 sequences were identical and genomic contexts could not explain the wide range of colistin resistances exhibited by the

Salmonella

strains. Nucleotide variants did explain phenotypic differences in motility and exopolysaccharide production. The observed linkage of mcr-9 to lactose metabolism, an array of heavy-metal detoxification systems, and other antibiotic resistance genes may reflect a coalescence of specialized phenotypes that improve the spread of colistin resistance in dairy facilities, much earlier than previously suspected.
Localized and Widespread Chronic Pain in Sexual and Gender Minority People – An Analysis of The PRIDE Study
Authors: Chadwick Andrea L. , Lisha Nadra E. , Lubensky Micah E. , Dastur Zubin , Lunn Mitchell R. , Obedin-Maliver Juno , Flentje Annesa
Published: November 2023

Sex related differences, without taking gender into account, in chronic pain have been widely researched over the past few decades in predominantly cisgender and heterosexual populations. Historically, chronic pain conditions have a higher incidence and prevalence in cisgender women, including but not limited to fibromyalgia, irritable bowel syndrome, and migraine. The goal of the present study was to identify and characterize the presence and characteristics of chronic pain in SM and GM persons using data from The PRIDE Study, which is the first large-scale, long-term national cohort health study of people who identify as lesbian, gay, bisexual, transgender, queer, or as another sexual or gender minority person. A total of 6189 adult participants completed The PRIDE Study 2022 Annual Questionnaire at the time of data analysis. A total of 2462 participants reported no chronic pain, leaving 2935 participants who reported experiencing chronic pain. The findings from this study highlight that chronic pain is present to a significant degree in sexual and gender minority adults who participated in The PRIDE Study with chronic spine pain being the most common location/region of pain. Notably, more than one-third of non-binary persons, transgender men, and people who selected another gender experienced chronic widespread pain, defined by having 3 or more total regions of chronic pain. The lowest prevalence of chronic widespread pain was among transgender women and cisgender men. When considering sexual orientation, the highest prevalence of widespread pain was in participants who selected another sexual orientation, followed by queer and asexual, demisexual, gray ace, with the lowest prevalence of chronic widespread pain being in those who identify as straight or heterosexual, bisexual, pansexual, gay, and lesbian. Future studies are planned to elucidate how a variety of biopsychosocial mechanisms may influence chronic pain in sexual and gender minority persons.
TCR-H: Machine Learning Prediction of T-cell Receptor Epitope Binding on Unseen Datasets
Authors: T. Rajitha Rajeshwar , Demerdash Omar , Smith Jeremy C.
Published: November 2023

AI/ML approaches to predicting T-cell receptor (TCR) epitope specificity achieve high performance metrics on test datasets which include sequences that are also part of the training set but fail to generalize to test sets consisting of epitopes and TCRs that are absent from the training set, i.e., unseen. We present TCR-H, a supervised classification Support Vector Machines model using physicochemical features trained on the largest dataset available to date using only experimentally validated non-binders as negative datapoints. TCR-H exhibits an area under the curve of the receiver-operator characteristic (AUC of ROC) of 0.87 for epitope ‘hard splitting’ (i.e., on test sets with all epitopes unseen), 0.92 for TCR hard splitting and 0.89 for ‘strict splitting’ in which neither the epitopes nor the TCRs in the test set are seen in the training data. TCR-H may thus represent a significant step towards general applicability of epitope:TCR specificity prediction.
Efficacy ofWolbachia-mediated sterility for control of dengue: emulation of a cluster randomized target trial
Authors: Lim Jue Tao , Mailepessov Diyar , Chong Chee Seng , Dickens Borame , Lai Yee Ling , Ng Youming , Deng Lu , Lee Caleb , Tan Li Yun , Chain Grace , Ho Soon Hoe , Chang Chia-Chen , Ma Pei , Bansal Somya , Lee Vernon , Sim Shuzhen , Tan Cheong Huat , Ng Lee Ching
Published: November 2023

Background

Matings between maleAedes aegyptimosquitoes infected withwAlbB strain ofWolbachiaand wildtype females yield non-viable eggs. We evaluated the efficacy of releasingwAlbB-infectedAe. aegyptimale mosquitoes to suppress dengue.

Methods

We specified the protocol of a two-arm cluster-randomised test-negative controlled trial (cRCT) and emulated it using a nationally representative test-negative/positive database of individuals reporting for febrile illness to any public hospital, general practitioner or polyclinic. We built a cohort of individuals who reside inWolbachialocations versus a comparator control group who do not reside inWolbachialocations. We emulated a constrained randomisation protocol used in cRCTs to balance dengue risk between intervention and control arms in the pre-intervention period. We used the inverse-probability weighting approach to further balance the intervention and control groups using a battery of algorithmically selected sociodemographic, environmental and anthropogenic variables. Intention-to-treat analyses was conducted to estimate the risk reduction of dengue givenWolbachiaexposure.

Findings

The final cohort consisted of 7,049 individuals residing in areas treated byWolbachiainterventions for at least 3 months and 69,216 individuals residing in non-treated areas in the same time period. Intention-to-treat analyses revealed that, compared with controls,Wolbachiareleases for 3, 6, 12 or more months was associated to a 47% (Odds ratio (OR): 0.53 [0.45-0.62]), 47% (OR: 0.53 [0.50-0.65]) and 59% (OR: 0.41 [0.39-0.50]) protective efficacy against dengue respectively. When exposed to 12 or more months ofWolbachiareleases, protective efficacy ranged from 36% (OR: 0.64 [0.58-0.96]) to 77% (OR: 0.23 [0.22-0.33]) dependent on township, and from 48% (OR: 0.52 [0.48-0.7]) to 78% (OR: 0.22 [0.09-0.32]) across years. The proportion of virologically confirmed dengue cases was lower overall in the intervention arm, and across each subgroup. Protective efficacies were found across all townships, years, age and sex subgroups, with higher durations ofWolbachiaexposure similarly associated to greater risk reductions of dengue.

Interpretation

Our results demonstrated the potential ofWolbachia-mediated sterility for strengthening dengue control in tropical cities, where dengue burden is the greatest.

Funding

This study was supported by funding from Singapore’s Ministry of Finance, Ministry of Sustainability and the Environment, National Environment Agency, and National Robotics Program. JTL is supported by the Ministry of Education (MOE), Singapore Start-up Grant. SB is supported by an MOE Tier 2 grant.
Loss ofSlc35a2alters development of the mouse cerebral cortex
Authors: Elziny Soad , Sran Sahibjot , Yoon Hyojung , Corrigan Rachel R. , Page John , Ringland Amanda , Lanier Anna , Lapidus Sara , Foreman James , Heinzen Erin L. , Iffland Philip , Crino Peter B. , Bedrosian Tracy A.
Published: November 2023

Brain somatic variants inSLC35A2are associated with clinically drug-resistant epilepsy and developmental brain malformations, including mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE).SLC35A2encodes a uridine diphosphate galactose translocator that is essential for protein glycosylation; however, the neurodevelopmental mechanisms by whichSLC35A2disruption leads to clinical and histopathological features remain unspecified. We hypothesized that focal knockout (KO) or knockdown (KD) ofSlc35a2in the developing mouse cortex would disrupt cerebral cortical development through altered neuronal migration and cause changes in network excitability. We usedin uteroelectroporation (IUE) to introduce CRISPR/Cas9 and targeted guide RNAs or short-hairpin RNAs to achieveSlc35a2KO or KD, respectively, during early corticogenesis. FollowingSlc35a2KO or KD, we observed disrupted radial migration of transfected neurons evidenced by heterotopic cells located in lower cortical layers and in the sub-cortical white matter.Slc35a2KO in neurons did not induce changes in oligodendrocyte number, suggesting that the oligodendroglial hyperplasia observed in MOGHE originates from distinct cell autonomous effects. Spontaneous seizures were not observed, but intracranial EEG recordings after focal KO showed a reduced seizure threshold following pentylenetetrazol injection. These results demonstrate thatSlc35a2KO or KDin vivodisrupts corticogenesis through altered neuronal migration.
Impact of Treatment Adherence and Inhalation Technique on asthma outcomes of Pediatric Patients: A Longitudinal Study
Authors: Lizano-Barrantes Catalina , Garin Olatz , Mayoral Karina , Dima Alexandra L. , Pont Angels , Caballero-Rabasco M. Araceli , Praena-Crespo Manuel , Valdesoiro-Navarrete Laura , Guerra María Teresa , Bercedo-Sanz Alberto , Ferrer Montse
Published: November 2023

Introduction

We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroids-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma.

Methods

Participants (6-14 years old) from the ARCA (Asthma Research in Children and Adolescents) cohort - a prospective, multicenter, observational study (NCT04480242) - were followed for a period from 6 months to 5 years, via computer-assisted telephone interviews and a smartphone application. The Medication Intake Survey–Asthma (MIS-A) was administered to assess the implementation stage of adherence; and the Inhalation Technique Questionnaire (InTeQ) to assess the five key steps when using an inhaler. Symptoms control was measured with the Asthma Control Questionnaire (ACQ), and HRQL with the EQ-5D and the PROMIS-Pediatric Asthma Impact Scale (PROMIS-PAIS). Multilevel longitudinal mixed models were constructed separately with symptom control, exacerbation occurrence, EQ-5D, and PROMIS-PAIS as dependent variables.

Results

Of 360 participants enrolled, 303 (1203 interviews) were included in the symptom control and exacerbation analyses, 265 (732) in the EQ-5D, and 215 (619) in the PROMIS-PAIS. Around 60% of participants were male and most underwent maintenance treatment with inhaled corticosteroids plus long-acting β-agonists in a fixed dose (68–74%). Within-person variability was 83.6% for asthma control, 98.6% for exacerbations, 36.4% for EQ-5D and 49.1% for PROMIS-PAIS. At within-person level, patients with higher adherence had better symptom control (p=0.002) and HRQoL over time (p=0.016). Patients with better inhalation technique reported worse HRQoL simultaneously (p=0.012), but better HRQoL in future assessments (p=0.012). Frequency of reliever use was associated with symptom control (p<0.001), exacerbation occurrence (p<0.001), and HRQoL (p=0.042); and boys were more likely to present better symptom control and HRQoL than girls.

Conclusion

Our results confirm longitudinal associations at within-person level of the two indicators of quality use of inhalers: for adherence to maintenance treatment with symptom control and HRQoL, and for inhalation technique with HRQoL. Although treatment adherence showed to be excellent, a third part of participants reported a suboptimal inhalation technique, highlighting the need of actions for improving asthma management of pediatric population.
The effect of goal type of user-generated content on consumers' compensatory consumption behavior
Authors: Zhang Hao , Meng Dewen , Lv Xiaolin
Published: November 2023

Purpose

The purpose of this research is to explore the effect of goal type of user-generated content (UGC) on consumers' intention of within-domain and across-domain compensatory consumption in closed social media platforms, the mediating effect of self-threat, self-enhancement and self-protection motivation and the moderating effect of self-efficacy.

Design/methodology/approach

Four between-subject experiments were conducted to verify the hypotheses presented in this research. Study 1a had a sample size of 60 respondents and examined the effect of goal type of UGC on compensatory consumption. Study1b replicated the effect by using a sample size of 60 respondents. Study 2 had a sample size of 70 respondents and verified the mediating role of self-threat, self-enhancement motivation and self-protection motivation. Study 3 examined self-efficacy as a critical moderator by using a sample of 255 participants.

Findings

Study 1a and Study 1b demonstrate that UGC with an attainment goal (vs maintenance goal) is more easily produced within-domain and across-domain compensatory consumption. Study 2 verifies that the effect of goal type of UGC on within-domain compensatory consumption is serially mediated by self-threat and self-enhancement motivation, and the effect of goal type of UGC on across-domain compensatory consumption is serially mediated by self-threat and self-protection motivation. Study 3 demonstrates that self-efficacy not only moderates the effects of self-threat on within-domain or across-domain compensatory consumption respectively, but also moderates the whole mediating path structure.

Originality/value

This research extends the understanding of UGC and addresses the inconclusive evidence of the impact of goal type of UGC on consumer compensatory behavior in the context of closed social media platforms. The authors identify the moderating role of self-efficacy, which explains why consumers adopt different compensatory strategies.
Post-lockdown loneliness and social isolation among French students
Authors: Dutertre Emmanuelle , Fouillet Cyril
Published: November 2023

Purpose

This paper aims to explore the protective and risk factors involved in student loneliness after the lockdown measures taken limiting social contact during the COVID-19 pandemic in France.

Design/methodology/approach

Using a cross-sectional survey methodology, the authors collected data on a sample of 546 students pursuing management education in a French business school in several campuses. Loneliness was measured by the three-item UCLA loneliness scale. Logistic regression analysis examined the factors influencing student loneliness.

Findings

The prevalence of loneliness was 23.4%. Risk factors for loneliness were social isolation especially in terms of intensity and isolation from friends (OR: 5.40), having a regular paid activity (OR: 1.62) and not getting academic help from other students (OR: 2.11) or taking meals alone during the lockdowns (OR: 1.94). Being a male student (OR: 0.47), practicing a sport (OR: 0.64) and studying at a specific campus (OR: 0.43) were protective factors.

Practical implications

Understanding protective and risk factors affecting student loneliness helps higher education decision-makers to take the necessary actions to enhance student well-being which have an effect on learning processes.

Originality/value

Loneliness is a major public health concern among students. Knowledge of the determinants for loneliness are limited and this article attempts to augment this by exploring several protective and risk indicators of loneliness among French students.
Time matters: Why ecological effects of microplastics might change over time
Authors: Speißer Benedikt
Published: November 2023

Research Highlight: Lozano, Y. M., Gordillo, H., Waldmann, W., & Rillig, M. C. (2023). Photodegradation modifies microplastic effects on soil properties and plant performance. Journal of Applied Ecology, https://doi.org/10.1111/1365‐2664.14514.

Plastics are omnipresent in daily life and so is plastic waste in the environment. Once there, plastic waste remains for a long time, slowly disintegrating into ever smaller particles including microplastics (particles <5 mm). Simultaneously, physical and chemical properties of these particles are modified due to aging processes. Although scientific awareness about microplastic effects on terrestrial ecosystems is recently increasing, current studies focused on the effects of pristine microplastics. However, modified properties due to aging could influence microplastic effects on terrestrial ecosystems and their components. In their current study, Lozano et al. provide first evidence that photodegradation can modify the effects of different microplastics on soil properties and plant performance, indicating that degradation could intensify microplastic effects on plant–soil systems. These results emphasise the need to better investigate how the global issue of plastic pollution affects ecosystems, also over the long term, and the need to stop the flow of plastics entering the environment.
Consumption of mite‐ripened cheese did not impair the physiological status of both the non‐immunosuppressed and immunosuppressed mice
Authors: Carvalho Michelle M , Cangussu Alex Sander , de Sousa Brito Hélio , da Silva Norma Machado , Matioli André L , Oliveira Eugênio E , Fortes Ferreira Célia L L , Fontan Gabrielle C R , De Dea Lindner Juliano
Published: November 2023

Cheese mites environment infestations have been recurrent and well‐known for a long time. Nevertheless, studies aiming to evaluate consumption safety have not yet been conducted, causing legislation in many countries to prohibit and destroy this type of product when detected. Here, we evaluated whether feeding upon cheeses ripened with Tyrophagus putrescentiae (Acari: Acaridae) mites would impair the physiological status of non‐immunosuppressed and immunosuppressed (cyclophosphamide‐treated) mice. Our results revealed the absence of any detrimental effects of eating mite‐ripened cheeses, which can support the advancements in the regularisation of cheeses ripened with mites.
Precise tactile stimulation of worker ants by a robotic manipulator reveals that individual responses are density‐ and context‐dependent
Authors: Rüegg Matthias , Motes‐Rodrigo Alba , Tuleu Alexandre , Stroeymeyt Nathalie , Richardson Thomas O. , Sakar Mahmut Selman , Keller Laurent
Published: November 2023

Ant workers are often specialized in specific tasks, and it is well‐established that the main task an ant performs in the colony can be used to predict its sensitivity and responses to task‐associated stimuli. An often‐overlooked aspect of ants' task specialization is that individuals often switch tasks throughout the day and are not always engaged in functional tasks. Furthermore, the tasks individuals engage in are often correlated with other context‐specific factors, such as worker density, which can independently influence individuals' behaviour. Given this intra‐individual variation in task engagement and its correlation with density, it is currently unknown how these two factors interact to modulate ants' sensitivity and responses to stimuli.

To address this question, we built a robotic manipulation system that allowed us to teleoperate a dummy inside ant colonies and to provide simulated antennations to ants when performing different tasks in areas with different worker densities. We coupled this manipulation system with a custom‐built automated tracking system (FORT) that allowed us to track individual identities and locations as well as to record the ants' responses to the dummy stimulation.

We found independent effects of task and worker density on ants' responsiveness and alarm towards the dummy. Ants were less likely to respond and be alarmed by the dummy when stimulated in areas with high worker density. Responsiveness but not alarm was further influenced by the task being performed, with ants doing broodcare being the least responsive. Our results suggest that ants' behaviour is density‐dependent and that ants experience a process of habituation to tactile stimulation. Additionally, ants' responsiveness is modulated by the task they are performing at a given time, showing that sensitivity to stimuli is context‐dependent.

Our robotic set‐up constitutes a valuable tool to systematically investigate social insect behaviour under unprecedented experimental control to unravel the individual‐level behavioural rules that underpin the organization of social insect colonies. The integrated system presented here opens new research avenues to empirically investigate the effects of more complex stimuli on social insect behaviour and has the potential to significantly further our understanding of decentralized collective systems.
Polygenic risk for schizophrenia, social dispositions, and pace of epigenetic aging: Results from the Young Finns Study
Authors: Saarinen Aino , Marttila Saara , Mishra Pashupati P. , Lyytikäinen Leo‐Pekka , Raitoharju Emma , Mononen Nina , Sormunen Elina , Kähönen Mika , Raitakari Olli , Hietala Jarmo , Keltikangas‐Järvinen Liisa , Lehtimäki Terho
Published: November 2023

Schizophrenia is often regarded as a disorder of premature aging. We investigated (a) whether polygenic risk for schizophrenia (PRSsch) relates to pace of epigenetic aging and (b) whether personal dispositions toward active and emotionally close relationships protect against accelerated epigenetic aging in individuals with high PRSsch. The sample came from the population‐based Young Finns Study (n = 1348). Epigenetic aging was measured with DNA methylation aging algorithms such as AgeAccelHannum, EEAAHannum, IEAAHannum, IEAAHorvath, AgeAccelHorvath, AgeAccelPheno, AgeAccelGrim, and DunedinPACE. A PRSsch was calculated using summary statistics from the most comprehensive genome‐wide association study of schizophrenia to date. Social dispositions were assessed in terms of extraversion, sociability, reward dependence, cooperativeness, and attachment security. We found that PRSsch did not have a statistically significant effect on any studied indicator of epigenetic aging. Instead, PRSsch had a significant interaction with reward dependence (p = 0.001–0.004), cooperation (p = 0.009–0.020), extraversion (p = 0.019–0.041), sociability (p = 0.003–0.016), and attachment security (p = 0.007–0.014) in predicting AgeAccelHannum, EEAAHannum, or IEAAHannum. Specifically, participants with high PRSsch appeared to display accelerated epigenetic aging at higher (vs. lower) levels of extraversion, sociability, attachment security, reward dependence, and cooperativeness. A rather opposite pattern was evident for those with low PRSsch. No such interactions were evident when predicting the other indicators of epigenetic aging. In conclusion, against our hypothesis, frequent social interactions may relate to accelerated epigenetic aging in individuals at risk for psychosis. We speculate that this may be explained by social‐cognitive impairments (perceiving social situations as overwhelming or excessively arousing) or ending up in less supportive or deviant social groups.
Bacteriophage‐based approach for treatment of urinary tract infections: a quick outlook
Authors: Grygorcewicz Bartłomiej , Gliźniewicz Marta , Jabłońska Joanna , Augustyniak Adrian , Olszewska Patrycja , Wojciuk Bartosz , Miłek Dominika , Serwin Natalia , Czajkowski Artur , Cecerska‐Heryć Elżbieta , Rakoczy Rafał , Cymbaluk‐Płoska Aneta
Published: November 2023

Urinary tract infections (UTIs) are among the most common bacterial infections affecting millions worldwide. The increasing emergence of antibiotic‐resistant bacteria has become a serious concern in managing UTIs. Therefore, there is a growing interest in using bacteriophages as an alternative or adjunct therapy for UTIs. Bacteriophages are viruses that infect and kill bacteria, making them a promising tool for treating UTIs caused by antibiotic‐resistant bacteria. This article provides a quick outlook on using bacteriophages to treat UTIs. We summarize the current understanding of the biology of bacteriophages, the challenges associated with developing phage‐based therapies, and the promising results of several case reports and clinical trials. We also highlight the potential of phage therapy as a valuable tool in the fight against antibiotic‐resistant UTIs. This quick outlook on a bacteriophage‐based approach for treating UTIs offers a timely and informative summary of the current research in this field.
Anti‐cathepsin D immunotherapy triggers both innate and adaptive anti‐tumour immunity in breast cancer
Authors: David Timothée , Mallavialle Aude , Faget Julien , Alcaraz Lindsay B. , Lapierre Marion , du Roure Pénélope Desroys , Laurent‐Matha Valérie , Mansouri Hanane , Jarlier Marta , Martineau Pierre , Roger Pascal , Guiu Séverine , Chardès Thierry , Liaudet‐Coopman Emmanuelle
Published: November 2023

Background and Purpose

Triple‐negative breast cancer (TNBC) has poorer outcomes than other breast cancers (BC), including HER2+ BC. Cathepsin D (CathD) is a poor prognosis marker overproduced by BC cells, hypersecreted in the tumour microenvironment with tumour‐promoting activity. Here, we characterized the immunomodulatory activity of the anti‐CathD antibody F1 and its improved Fab‐aglycosylated version (F1M1) in immunocompetent mouse models of TNBC (C57BL/6 mice harbouring E0771 cell grafts) and HER2‐amplified BC (BALB/c mice harbouring TUBO cell grafts).

Experimental Approach

CathD expression was evaluated by western blotting and immunofluorescence, and antibody binding to CathD by ELISA. Antibody anti‐tumour efficacy was investigated in mouse models. Immune cell recruitment and activation were assessed by immunohistochemistry, immunophenotyping, and RT‐qPCR.

Key Results

F1 and F1M1 antibodies remodelled the tumour immune landscape. Both antibodies promoted innate antitumour immunity by preventing the recruitment of immunosuppressive M2‐polarized tumour‐associated macrophages (TAMs) and by activating natural killer cells in the tumour microenvironment of both models. This translated into a reduction of T‐cell exhaustion markers in the tumour microenvironment that could be locally supported by enhanced activation of anti‐tumour antigen‐presenting cell (M1‐polarized TAMs and cDC1 cells) functions. Both antibodies inhibited tumour growth in the highly‐immunogenic E0771 model, but only marginally in the immune‐excluded TUBO model, indicating that anti‐CathD immunotherapy is more relevant for BC with a high immune cell infiltrate, as often observed in TNBC.

Conclusion and implication

Anti‐CathD antibody‐based therapy triggers the anti‐tumour innate and adaptive immunity in preclinical models of BC and is a promising immunotherapy for immunogenic TNBC.
Atypical Spitz tumor with SQSTM1::NTRK2 fusion: Report of a case with unique spindled cell features
Authors: Phillips Gregory S. , Mengden‐Koon Stephanie , Dhossche Julie , LeBoit Philip E. , Goldstein Alisa M. , Lee Ina , Raffeld Mark , Papanicolau‐Sengos Antonios , Sargen Michael R. , Chung Jina
Published: November 2023

A host of signature genetic alterations have been demonstrated in Spitz neoplasms, most notably fusions of kinase genes (including BRAF, ALK, ROS1, NTRK1, NTRK3, RET, MET, MAP3K8) or variants in HRAS. While there are multiple reports of rearrangements involving NTRK1 and NTRK3 in Spitz tumors, there are very few reports of NTRK2‐rearranged Spitz nevi in the literature. This report presents an NTRK2‐rearranged atypical Spitz tumor with spindled cell features. The patient was a 6‐year‐old female with a growing pigmented papule on the back. Histopathological evaluation revealed an asymmetric, biphasic, compound proliferation of melanocytes featuring an epithelioid cell population arranged as variably sized nests and single cells along the basal layer with extension down adnexa, as well as a population of spindled melanocytes with desmoplastic features and loss of Melan‐A expression in the dermis. There was partial loss of p16 expression in the epidermal component and diffuse loss in the dermal component. Immunohistochemistry for PRAME, ALK, NTRK1, HRAS Q61R, p53, and BRAF V600E were negative. A SQSTM1::NTRK2 fusion was identified by RNA sequencing. No TERT promoter hotspot variants were detected. This case report expands the known histopathologic spectrum of genetic alterations in Spitz neoplasms.
Incretin‐based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes: A systematic review and meta‐analysis of observational studies
Authors: Igweokpala Samuel , Sule Naheemot Olaoluwa , Douros Antonios , Yu Oriana H. Y. , Filion Kristian B.
Published: November 2023

Aim

The results from the SUSTAIN‐6 trial generated some uncertainty regarding the association between incretin‐based drugs [dipeptidyl peptidase‐4 (DPP‐4) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs)] and the risk of diabetic retinopathy. Our objective was to synthesize the available evidence from observational studies regarding the use of incretin‐based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes.

Materials and Methods

We systemically searched Cochrane Library, Embase and Medline to identify observational studies of interest. Risk of bias was assessed using the ROBINS‐I tool. Data from included studies were pooled using the DerSimonian and Laird random‐effect model with the Hartung‐Knapp extension.

Results

We included 14 studies in the systematic review, with 10 examining DPP‐4 inhibitors and seven examining GLP‐1 RAs. Nine studies investigated incident diabetic retinopathy, six investigated diabetic retinopathy progression and two investigated both outcomes. Seven studies were at moderate risk of bias, four at serious risk of bias and three at critical risk of bias. Data pooled across studies showed no association between the use of DPP‐4 inhibitors (risk ratio: 0.98, 95% confidence interval: 0.83, 1.17) or GLP‐1 RAs (risk ratio: 0.87, 95% confidence interval: 0.56, 1.34) and the risk of diabetic retinopathy.

Conclusion

This study suggests that the use of incretin‐based drugs is not associated with the risk of diabetic retinopathy among individuals with type 2 diabetes. However, these findings should be interpreted with caution considering the limited quality of some of the available evidence.
Personal preferences for treatment and care during and after a First Episode Psychosis: A qualitative study
Authors: van der Heijden‐Hobus Inge M. W. , Rosema Bram‐Sieben , Vorstman Jacob A. S. , Kas Martien J. H. , Franke Sigrid K. , Boonstra Nynke , Sommer Iris E. C.
Published: November 2023

Aim

A first episode of psychosis (FEP) is a stressful, often life‐changing experience. Scarce information is available about personal preferences regarding their care needs during and after a FEP. Whereas a more thorough understanding of these preferences is essential to aid shared decision‐making during treatment and improve treatment satisfaction.

Methods

Face‐to‐face interviews with participants in remission of a FEP were set up, addressing personal preferences and needs for care during and after a FEP. The interviews were conducted by a female and a male researcher, the latter being an expert with lived experience.

Results

Twenty individuals in remission of a FEP were interviewed, of which 16 had been hospitalized. The distinguished themes based on personal preferences were tranquillity, peace and quietness, information, being understood, support from significant others, and practical guidance in rebuilding one's life. Our findings revealed that the need for information and the need to be heard were often not sufficiently met. For 16/20 participants, the tranquillity of inpatient treatment of the FEP was predominantly perceived as a welcome safe haven. The presence and support of family and close friends were mentioned as an important factor in the process of achieving remission.

Conclusions

The current exploratory study showed that patients were able to indicate their personal needs. Important findings are the need for information and the need to be heard. Interestingly, hospitalization was mostly seen as an opportunity to achieve tranquillity. More lived experience expertise is needed to elucidate the needs of individuals in the early phase of a FEP to aid people who are recovering from their first psychosis in rebuilding their lives again.
Early phase psychosis and criminal conviction in United States adults
Authors: Webster Kyle D. , Gunter Tracy D. , Vohs Jenifer L. , Breier Alan
Published: November 2023

Aim

Individuals experiencing early phase psychosis (EPP) are at increased risk for legal involvement. In prior studies, between 14% and 75% of individuals with EPP reported a history of criminal offending behaviour, criminal charges, or criminal convictions. To better understand the frequency of criminal conviction in a specialty treatment clinic serving EPP clients, the research team supplemented self‐reported data from the clinic intake with information from publicly available databases.

Methods

In this sample of 309 adults, approximately one quarter of patients (n = 76) self‐reported a history of arrest, incarceration, probation, or parole within 6 months of enrolment in a treatment clinic. The research team expanded upon this and collected data from a public database of court proceedings in Indiana for all clinic participants before and after enrolment.

Results

Thirty‐nine percent (n = 122) had three or more traffic tickets or a conviction for an ordinance violation, misdemeanour, or felony in the state of Indiana as an adult. This is over two times the national average. Drug and alcohol related convictions were the most common single conviction type, and 29% (n = 89) of subjects experienced at least one incarceration.

Conclusions

These data highlight the need for specialty clinics to partner with professionals with expertise in the prevention and management of criminal behaviour. Future studies should examine risk factors for individuals experiencing EPP and criminal conviction.
Harnessing the power of regional baselines for broad‐scale genetic stock identification: A multistage, integrated, and cost‐effective approach
Authors: Hsu Bobby , Habicht Christopher
Published: November 2023

In mixed‐stock fishery analyses, genetic stock identification (GSI) estimates the contribution of each population to a mixture and is typically conducted at a regional scale using genetic baselines specific to the stocks expected in that region. Often these regional baselines cannot be combined to produce broader geographical baselines due to non‐overlapping populations and genetic markers. In cases where the mixture contains stocks spanning across a wide area, a broad‐scale baseline is created, but often at the cost of resolution. Here, we introduce a new GSI method to harness the resolution capabilities of baselines developed for regional applications in the analysis of mixtures containing individuals from a broad geographic range. This method employs a multistage framework that allows disparate baselines to be used in a single integrated process that produces estimates along with the propagated errors from each stage. All individuals in the mixture sample are required to be genotyped for all genetic markers in the baselines used by this model, but the baselines do not require overlap in genetic markers or populations representing the broad‐scale or regional baselines. We demonstrate the utility of our integrated multistage model using a synthesized data set made up of Chinook salmon, Oncorhynchus tshawytscha, from the North Bering Sea of Alaska. The results show an improved accuracy for estimates using an integrated multistage framework, compared to the conventional framework of using separate hierarchical steps. The integrated multistage framework allows GSI of a wide geographic area without first developing a large scale, high‐resolution genetic baseline or dividing a mixture sample into smaller regions beforehand. This approach is more cost‐effective than updating range‐wide baselines with all regionally important markers.
Preparation of bionic nacre by “freezing‐mineralization” and their electrical, thermal, and mechanical properties
Authors: Wu Canfeng , Li Yi , Yao Yingbang
Published: November 2023

Natural nacre has attracted a lot of attention due to its superior mechanical properties. It is generally made up of 95% flake calcium carbonate and 5% organic matter. In this work, we prepared the bionic nacre material using the “freezing‐mineralization” method. The bionic material exhibits a microstructure that is quite similar to that of natural material and shows a high dielectric constant. The thermal conductivity in the in‐plane direction reaches 1.15 W/(m•K) at ambient temperature, which is 2.25 times higher than the out‐of‐plane direction's, clearly demonstrating an anisotropic behavior. Additionally, the mechanical performance of the biomimetic material can be on par with that of natural materials with a maximum breakdown stress of 51.4 MPa. Our results prove that the “freezing‐mineralization” method is essential to developing bionic nacre materials.
Corrosion mechanism and behavior of nickel slag on semi‐rebonded magnesia‐chrome brick for top‐blown furnace
Authors: Zong Hongxing , Lu Miaomiao , Zheng Jianghua , Li Bin , Xin Yalou , Ren Xuegen , Du Xueyan
Published: November 2023

The corrosion behavior and mechanism of nickel slag on semi‐rebonded magnesia‐chrome brick are investigated. The variations in the specimens before and after corrosion were studied using microstructure, phase composition, and thermodynamic simulations. The results reveal that at high temperatures, the metal oxides in nickel slag easily react with Cr2O3 to generate Cr‐spinel, and the isolation layer forms a continuous phase on the surface of the refractory. The appearance of the isolation layer causes the nickel slag corrosion process on semi‐rebonded magnesia‐chrome brick to shift from direct to indirect corrosion controlled by ion diffusion, effectively blocking the continuous penetration of Ca2+ and Si4+ in the slag inside the refractories. As a result, the semi‐rebonded magnesia‐chrome brick resists nickel slag corrosion extremely well.
Potential role of epithelial–mesenchymal transition induced by periodontal pathogens in oral cancer
Authors: Ma Yiwei , Yu Yingyi , Yin Yuqing , Wang Liu , Yang Huishun , Luo Shiyin , Zheng Qifan , Pan Yaping , Zhang Dongmei
Published: November 2023

With the increasing incidence of oral cancer in the world, it has become a hotspot to explore the pathogenesis and prevention of oral cancer. It has been proved there is a strong link between periodontal pathogens and oral cancer. However, the specific molecular and cellular pathogenic mechanisms remain to be further elucidated. Emerging evidence suggests that periodontal pathogens‐induced epithelial–mesenchymal transition (EMT) is closely related to the progression of oral cancer. Cells undergoing EMT showed increased motility, aggressiveness and stemness, which provide a pro‐tumour environment and promote malignant metastasis of oral cancer. Plenty of studies proposed periodontal pathogens promote carcinogenesis via EMT. In the current review, we discussed the association between the development of oral cancer and periodontal pathogens, and summarized various mechanisms of EMT caused by periodontal pathogens, which are supposed to play an important role in oral cancer, to provide targets for future research in the fight against oral cancer.
The role of Department of Veterans Affairs community‐based outpatient clinics in enhancing rural access to geriatrics telemedicine specialty care
Authors: Pimentel Camilla B. , Dryden Eileen M. , Nearing Kathryn A. , Kernan Laura M. , Kennedy Meaghan A. , Hung William W. , Riley Jessica , Moo Lauren R.
Published: November 2023

Background

Half of the 4.7 M veterans who reside in rural communities and rely on U.S. Department of Veterans Affairs (VA) health care are older (≥65). Their rurality presents unique challenges, including a shortage of clinicians skilled in geriatric medicine. Community‐based outpatient clinics (CBOCs) help extend VA's geographic reach but are typically located in under‐resourced settings. Telemedicine may increase access to care, but little is known about CBOCs' capacity to leverage telemedicine to meet older patients' needs. We identified organizational barriers and facilitators to the use of geriatric telemedicine specialty care from the perspective of rural clinicians and staff.

Methods

From February–April 2020, we interviewed CBOC clinicians and staff (N = 50) from 13 rural CBOCs affiliated with four VA Geriatric Research Education and Clinical Centers. Semi‐structured interviews addressed patient population characteristics; CBOC location, staffing, and in‐house resources; use of VA specialty care services; and telemedicine use. We developed a codebook using an iterative process and Gale's Framework Method thematically organize and analyze data.

Results

Respondents perceived that their CBOCs serve a predominantly older patient population. Four characteristics enabled CBOCs to offer geriatric telemedicine specialty care: partnerships with larger VA Medical Center teams; social worker/telehealth clinical technician knowledge of geriatrics and telehealth resources; periodic outreach/education from geriatric specialists; and routine use of other telehealth services. Barriers included: constraints on clinic space and unstable internet for telemedicine visits; staffing challenges leading to limited familiarity with telemedicine resources; and clinician and staff perceptions of older veterans' preference for in‐person visits.

Conclusions

Telemedicine is an important modality to enhance access to care for an increasingly older and medically complex patient population. Although rural CBOCs provide a large portion of care to VA's growing geriatric population, staff are insufficiently trained in geriatrics, work in resource‐poor settings, and are largely unaware of VA telemedicine programs designed to support them.
Relationship between masseter muscle activity during wakefulness and temporomandibular disorder‐related symptoms
Authors: Maeda‐Iino Aya , Osako Yuki , Nakagawa Shoko , Takahashi Kotaro , Oga Yasuhiko , Furukawa‐Sainoki Minami , Harada Marina , Fukushima Mika , Miyawaki Shouichi
Published: November 2023

Background

Masseter muscle activity during wakefulness may be associated with temporomandibular disorder (TMD)‐related symptoms, psychosocial status and pain‐related disability; however, this relationship is unclear.

Objectives

This study aimed to determine the relationship between masseter muscle electromyography (EMG) burst/duration during wakefulness and TMD‐related symptoms, psychosocial status and pain‐related disability.

Methods

Sixty participants were assessed masseter muscle activity during wakefulness using a data‐logger‐type ultraminiature EMG system and TMD‐related symptoms, psychosocial status and pain‐related disability through Axis I and II of the diagnostic criteria for TMD (DC/TMD). EMG bursts lasting longer than 0.25 s but less than 2.0 s and those lasting longer than 2.0 s were classified as phasic and tonic bursts, respectively.

Results

Participants with palpation‐related pain in the temporalis and masseter muscles, as assessed through the DC/TMD examination form in Axis I, had more bursts (number/h) (p = .035 and p = .009, respectively) and longer duration (time/h) (p = .013 and p = .004, respectively) of tonic bursts of the masseter muscle during wakefulness. Participants with palpation‐related pain in the masseter muscles had higher oral behaviour scores during wakefulness using Axis II (p = .001), which affected the number and duration of tonic bursts of the masseter muscle activity during wakefulness (p = .011 and p = .007, respectively).

Conclusion

As tonic bursts mainly reflect clenching, individuals with pain in the masseter muscles by palpation may have a high frequency and longer duration of clenching, as well as a high frequency of oral behaviours during wakefulness.
Unique Moon sites could be ‘lost forever’ in mining rush
Authors: Clery Daniel
Published: November 2023

Researchers seek protection for pristine areas on Moon’s far side and polar regions
Simian immunodeficiency virus and storage buffer: Field-friendly preservation methods for RNA viral detection in primate feces
Authors: Wilde Tessa H. C. , Shukla Rajni Kant , Madden Christopher , Vodovotz Yael , Sharma Amit , McGraw W. Scott , Hale Vanessa L.
Published: November 2023

Wild non-human primates carry many types of RNA viruses, including simian immunodeficiency virus (SIV), simian foamy virus, simian T-cell leukemia virus, and hepatitis C virus. These viruses can also infect humans via zoonotic transmission through handling and consumption of primate bushmeat. Characterizing viral prevalence and shedding in natural hosts is critical to understand infection and transmission risks within and between primate species. Here, we sought to identify a robust “field-friendly” method (i.e., without freezing or refrigeration) for preserving viral RNA, specifically SIV, in primate fecal samples. Fecal samples were collected from a mantled guereza colobus (
Colobus guereza
) housed at the Columbus Zoo and Aquarium. Samples were homogenized and inoculated with three concentrations (low, medium, and high) of inactivated SIV and preserved in four different storage buffers (DNA/RNA Shield, RNA
later
, 95% Ethanol, and Viral Transport Medium). SIV viral RNA was then extracted from samples at four time points (1 week, 4 weeks, 8 weeks, and 12 weeks) to determine the efficacy of each buffer for preserving SIV RNA. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used for the detection and quantification of viral RNA. At all concentrations, DNA/RNA Shield yielded the highest average SIV virion concentrations. We then successfully validated this approach using fecal samples from known SIV-positive and SIV-negative sooty mangabeys (
Cercocebus atys
) housed at Emory National Primate Research Center. Our results indicate that DNA/RNA Shield is an optimal “field-friendly” buffer for preserving SIV RNA in fecal samples over time and may also be effective for preserving other RNA viruses in feces.

IMPORTANCE

Simian immunodeficiency virus (SIV), which originated in African monkeys, crossed the species barrier into humans and ultimately gave rise to HIV and the global HIV/AIDS epidemic. While SIV infects over 40 primate species in sub-Saharan Africa, testing for RNA viruses in wild primate populations can be challenging. Optimizing field-friendly methods for assessing viral presence/abundance in non-invasively collected biological samples facilitates the study of viruses, including potentially zoonotic viruses, in wild primate populations. This study compares SIV RNA preservation and recovery from non-human primate feces stored in four different buffers. Our results will inform future fieldwork and facilitate improved approaches to characterizing prevalence, shedding, and transmission of RNA viruses like SIV in natural hosts including wild-living non-human primates.