bluuebunny/crossref_metadata_2025 huggingface dataset:
In utero ethanol exposure induces mitochondrial DNA damage and inhibits mtDNA repair in developing brain
Authors: Darbinian Nune , Darbinyan Armine , Merabova Nana , Kassem Myrna , Tatevosian Gabriel , Amini Shohreh , Goetzl Laura , Selzer Michael E.
Published: August 2023

Introduction

Mitochondrial dysfunction is postulated to be a central event in fetal alcohol spectrum disorders (FASD). People with the most severe form of FASD, fetal alcohol syndrome (FAS) are estimated to live only 34 years (95% confidence interval, 31 to 37 years), and adults who were born with any form of FASD often develop early aging. Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage, hallmarks of aging, are postulated central events in FASD. Ethanol (EtOH) can cause mtDNA damage, consequent increased oxidative stress, and changes in the mtDNA repair protein 8-oxoguanine DNA glycosylase-1 (OGG1). Studies of molecular mechanisms are limited by the absence of suitable human models and non-invasive tools.

Methods

We compared human and rat EtOH-exposed fetal brain tissues and neuronal cultures, and fetal brain-derived exosomes (FB-Es) from maternal blood. Rat FASD was induced by administering a 6.7% alcohol liquid diet to pregnant dams. Human fetal (11–21 weeks) brain tissue was collected and characterized by maternal self-reported EtOH use. mtDNA was amplified by qPCR. OGG1 and Insulin-like growth factor 1 (IGF-1) mRNAs were assayed by qRT-PCR. Exosomal OGG1 was measured by ddPCR.

Results

Maternal EtOH exposure increased mtDNA damage in fetal brain tissue and FB-Es. The damaged mtDNA in FB-Es correlated highly with small eye diameter, an anatomical hallmark of FASD. OGG1-mediated mtDNA repair was inhibited in EtOH-exposed fetal brain tissues. IGF-1 rescued neurons from EtOH-mediated mtDNA damage and OGG1 inhibition.

Conclusion

The correlation between mtDNA damage and small eye size suggests that the amount of damaged mtDNA in FB-E may serve as a marker to predict which at risk fetuses will be born with FASD. Moreover, IGF-1 might reduce EtOH-caused mtDNA damage and neuronal apoptosis.
Emerging therapeutic role of gut microbial extracellular vesicles in neurological disorders
Authors: Sun Bowen , Sawant Harshal , Borthakur Alip , Bihl Ji Chen
Published: August 2023

Extracellular vesicles (EVs) serve as cell-to-cell and inter-organ communicators by conveying proteins and nucleic acids with regulatory functions. Emerging evidence shows that gut microbial-released EVs play a pivotal role in the gut-brain axis, bidirectional communication, and crosstalk between the gut and the brain. Increasing pre-clinical and clinical evidence suggests that gut bacteria-released EVs are capable of eliciting distinct signaling to the brain with the ability to cross the blood–brain barrier, exerting regulatory function on brain cells such as neurons, astrocytes, and microglia, via their abundant and diversified protein and nucleic acid cargo. Conversely, EVs derived from certain species of bacteria, particularly from gut commensals with probiotic properties, have recently been shown to confer distinct therapeutic effects on various neurological disorders. Thus, gut bacterial EVs may be both a cause of and therapy for neuropathological complications. This review marshals the basic, clinical, and translational studies that significantly contributed to our up-to-date knowledge of the therapeutic potential of gut microbial-derived EVs in treating neurological disorders, including strokes, Alzheimer’s and Parkinson’s disease, and dementia. The review also discusses the newer insights in recent studies focused on developing superior therapeutic microbial EVs via genetic manipulation and/or dietary intervention.
A new diagnostic tool for brain disorders: extracellular vesicles derived from neuron, astrocyte, and oligodendrocyte
Authors: Wang Xueying , Yang Huihui , Liu Chunyu , Liu Kefu
Published: August 2023

Brain disorders are the leading cause of disability worldwide, affecting people’s quality of life and causing economic burdens. The current clinical diagnosis of brain disorders relies solely on individual phenotypes and lacks accurate molecular biomarkers. An emerging field of research centers around extracellular vesicles (EVs), nanoscale membrane vesicles which can easily cross the blood–brain barrier. EVs in the blood are derived from various tissues, including the brain. Therefore, purifying central nervous system (CNS)-derived EVs from the blood and analyzing their contents may be a relatively non-invasive way to analyze brain molecular alterations and identify biomarkers in brain disorders. Recently, methods for capturing neuron-derived EVs (NDEs), astrocyte-derived EVs (ADEs), and oligodendrocyte-derived EVs (ODEs) in peripheral blood were reported. In this article, we provide an overview of the research history of EVs in the blood, specifically focusing on biomarker findings in six major brain disorders (Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, depression, and autism spectrum disorder). Additionally, we discuss the methodology employed for testing CNS-derived EVs. Among brain disorders, Alzheimer’s disease has received the most extensive attention in EV research to date. Most studies focus on specific molecules, candidate proteins, or miRNAs. Notably, the most studied molecules implicated in the pathology of these diseases, such as Aβ, tau, and α-synuclein, exhibit good reproducibility. These findings suggest that CNS-derived EVs can serve as valuable tools for observing brain molecular changes minimally invasively. However, further analysis is necessary to understand the cargo composition of these EVs and improve isolation methods. Therefore, research efforts should prioritize the analysis of CNS-derived EVs’ origin and genome-wide biomarker discovery studies.
Machine learning for predicting breast-conserving surgery candidates after neoadjuvant chemotherapy based on DCE-MRI
Authors: Chen Zhigeng , Huang Manxia , Lyu Jianbo , Qi Xin , He Fengtai , Li Xiang
Published: August 2023

Purpose

This study aimed to investigate a machine learning method for predicting breast-conserving surgery (BCS) candidates, from patients who received neoadjuvant chemotherapy (NAC) by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) obtained before and after NAC.

Materials and methods

This retrospective study included 75 patients who underwent NAC and breast surgery. First, 3,390 features were comprehensively extracted from pre- and post-NAC DCE-MRIs. Then patients were then divided into two groups: type 1, patients with pathologic complete response (pCR) and single lesion shrinkage; type 2, major residual lesion with satellite foci, multifocal residual, stable disease (SD), and progressive disease (PD). The logistic regression (LR) was used to build prediction models to identify the two groups. Prediction performance was assessed using the area under the curve (AUC), accuracy, sensitivity, and specificity.

Results

Radiomics features were significantly related to breast cancer shrinkage after NAC. The combination model achieved an AUC of 0.82, and the pre-NAC model was 0.64, the post-NAC model was 0.70, and the pre-post-NAC model was 0.80. In the combination model, 15 features, including nine wavelet-based features, four Laplacian-of-Gauss (LoG) features, and two original features, were filtered. Among these selected were four features from pre-NAC DCE-MRI, six were from post-NAC DCE-MRI, and five were from pre-post-NAC features.

Conclusion

The model combined with pre- and post-NAC DCE-MRI can effectively predict candidates to undergo BCS and provide AI-based decision support for clinicians with ensured safety. High-order (LoG- and wavelet-based) features play an important role in our machine learning model. The features from pre-post-NAC DCE-MRI had better predictive performance.
Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial)
Authors: Garcia-Tejedor Amparo , Ortega-Exposito Carlos , Salinas Sira , Luzardo-González Ana , Falo Catalina , Martinez-Pérez Evelyn , Pérez-Montero Héctor , Soler-Monsó M. Teresa , Bajen Maria-Teresa , Benitez Ana , Ortega Raul , Petit Anna , Guma Anna , Campos Miriam , Plà Maria J. , Pernas Sonia , Peñafiel Judith , Yeste Carlos , Gil-Gil Miguel , Guedea Ferran , Ponce Jordi , Laplana Maria
Published: August 2023

Introduction

Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects.

Methods and analyses

This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival.

Discussion

This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity.

Ethics and dissemination

The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results.

Trial registration

ClinicalTrials.gov, identifier number NCT04889924.
Increase in pediatric recurrent fever evaluations during the first year of the COVID-19 pandemic in North America
Authors: Mansfield Leanne M. , Lapidus Sivia K. , Romero Samira Nazzar , Moorthy Lakshmi N. , Adler-Shohet Felice C. , Hollander Matthew , Cherian Julie , Twilt Marinka , Lionetti Geraldina , Mohan Smriti , DeLaMora Patricia A. , Durrant Karen L. , Muskardin Theresa Wampler , Correia Marques Mariana , Onel Karen B. , Dedeoglu Fatma , Gutierrez Maria J. , Schulert Grant ,   the CARRA Autoinflammatory Network Consortium for the CARRA PFAPA/Autoinflammatory Working Group
Published: August 2023

The impact of the COVID-19 pandemic on new diagnoses of recurrent fevers and autoinflammatory diseases is largely unknown. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA/AID Working Group aimed to investigate the impact of the COVID-19 pandemic on the number of pediatric patients evaluated for recurrent fevers and autoinflammatory diseases in North America. The absolute number of new outpatient visits and the proportion of these visits attributed to recurrent fever diagnoses during the pre-pandemic period (1 March 2019–29 February 2020) and the first year of the COVID-19 pandemic (1 March 2020–28 February 2021) were examined. Data were collected from 27 sites in the United States and Canada. Our results showed an increase in the absolute number of new visits for recurrent fever evaluations in 21 of 27 sites during the COVID-19 pandemic compared to the pre-pandemic period. The increase was observed across different geographic regions in North America. Additionally, the proportion of new visits to these centers for recurrent fever in relation to all new patient evaluations was significantly higher during the first year of the pandemic, increasing from 7.8% before the pandemic to 10.9% during the pandemic year (p < 0.001). Our findings showed that the first year of the COVID-19 pandemic was associated with a higher number of evaluations by pediatric subspecialists for recurrent fevers. Further research is needed to understand the reasons behind these findings and to explore non-infectious triggers for recurrent fevers in children.
Cost-effectiveness analysis of once-daily oral semaglutide versus placebo and subcutaneous glucagon-like peptide-1 receptor agonists added to insulin in patients with type 2 diabetes in China
Authors: Feng Zhen , Tong Wai Kei , Zhang Xinyue , Tang Zhijia
Published: August 2023

Introduction: Oral semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that improves glycated hemoglobin levels and body weight in patients with type 2 diabetes (T2DM). We aim to evaluate the cost-effectiveness of once-daily oral semaglutide in comparison to placebo and injectable GLP-1 RAs in Chinese patients with T2DM inadequately controlled on basal insulin.

Methods: The United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS OM2.1) was used to estimate the cost-effectiveness by calculating the incremental cost-effectiveness ratio (ICER). Baseline characteristics of the simulation cohort were obtained from the PIONEER 8 trial. Utility and safety inputs were derived from a network meta-analysis of 12 trials. Direct medical costs were retrieved from published literature and discounted at an annual rate of 5%. We used a willingness-to-pay (WTP) threshold of $36,528.3 per quality-adjusted life-year (QALY) gained. Scenario analysis, and one-way and probabilistic sensitivity analysis were performed.

Results: The effectiveness of oral semaglutide was 10.39 QALYs with a total cost of $30,223.10, while placebo provided 10.13 QALYs at a lower total cost of $20,039.19. Oral semaglutide was not cost-effective at an ICER of $39,853.22 and $88,776.61 per QALY compared to placebo and exenatide at the WTP. However, at an annual price of $1,871.9, it was cost-effective compared with dulaglutide, liraglutide, and lixisenatide. The model was most sensitive to the discount rate and annual cost of oral semaglutide. The price of oral semaglutide needed to be reduced to $1,711.03 per year to be cost-effective compared to placebo and other injectable GLP-1 RAs except for exenatide and semaglutide injection.

Conclusion: We found that once-daily oral semaglutide, at a comparable price of semaglutide injection, proves to be a cost-effective add-on therapy to insulin for Chinese patients with T2DM, especially when compared to subcutaneous GLP-1 RAs other than injectable semaglutide and exenatide. However, to achieve cost-effectiveness in comparison to placebo, further cost reduction of oral semaglutide is necessary. The estimated annual cost of $1,711.03 for oral semaglutide demonstrates a more cost-effective option than placebo, highlighting its potential value in the management of T2DM.
Development of a robust UPLC-MS/MS method for the quantification of riluzole in human plasma and its application in pharmacokinetics
Authors: Sun Zhuo , Liu Xin , Zuo Wei , Fu Qiang , Xu Tingting , Cui Liying , Zhang Bo , Peng Ying
Published: August 2023

Introduction: The aim of the present study was to establish a simple method for the determination of riluzole in human plasma by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and apply it for the determination of riluzole in amyotrophic lateral sclerosis (ALS) patients.

Methods: Samples were prepared by protein precipitation and were then gradient-eluted on a column of ACQUITY UPLC® HSS T3 by using 0.1% formic acid acetonitrile and 0.1% formic acid water as the mobile phase. Detection was performed on a Xevo TQ-S tandem mass spectrometer in the multiple-reaction monitoring mode using positive electrospray ionization. Validation was performed in the range of 5–800 ng/mL.

Results and discussion: Three batches of precision accuracy, selectivity, matrix effects, extraction recovery, and stability were also verified and met the requirements. The results showed that the method was reliable and successfully applied to the pharmacokinetics study of riluzole in Chinese amyotrophic lateral sclerosis patients. Meanwhile, in comparison with other prior published methods, our method has the advantages of simple sample preparation, relatively short running time, and small plasma sample consumption, which represented a high-throughput sample determination potential.
TRAIL and its receptors in cardiac diseases
Authors: Grisanti Laurel A.
Published: August 2023

Cardiovascular disease is a leading cause of death worldwide. Loss of cardiomyocytes that occurs during many types of damage to the heart such as ischemic injury and stress caused by pressure overload, diminishes cardiac function due to their limited regenerative capacity and promotes remodeling, which further damages the heart. Cardiomyocyte death occurs through two primary mechanisms, necrosis and apoptosis. Apoptosis is a highly regulated form of cell death that can occur through intrinsic (mitochondrial) or extrinsic (receptor mediated) pathways. Extrinsic apoptosis occurs through a subset of Tumor Necrosis Receptor (TNF) family receptors termed “Death Receptors.” While some ligands for death receptors have been extensively studied in the heart, such as TNF-α, others have been virtually unstudied. One poorly characterized cardiac TNF related ligand is TNF-Related Apoptosis Inducing Ligand (TRAIL). TRAIL binds to two apoptosis-inducing receptors, Death Receptor (DR) 4 and DR5. There are also three decoy TRAIL receptors, Decoy Receptor (DcR) 1, DcR2 and osteoprotegerin (OPG). While TRAIL has been extensively studied in the cancer field due to its ability to selectively induce apoptosis in transformed cell types, emerging clinical evidence points towards a role for TRAIL and its receptors in cardiac pathology. This article will highlight our current understanding of TRAIL and its receptors in normal and pathological conditions in the heart.
Critical weather limits for paddy rice under diverse ecosystems of India
Authors: Bal Santanu Kumar , Sattar Abdus , Nidhi  , Chandran Malamal Alickal Sarath , Subba Rao Abburi Venkata M. , Manikandan Narayanan , Banerjee Saon , Choudhary Jawahar L. , More Vijay G. , Singh Chandra B. , Sandhu Sandeep S. , Singh Vinod Kumar
Published: August 2023

Rice yields are largely influenced by variability in weather. Here, we demonstrate the effect of weather variables viz., maximum and minimum temperatures, rainfall, morning and evening relative humidity, bright sunshine hours on the yield of rice cv. Swarna, grown across five rice ecologies of India through field experiments during kharif (wet) season (Jun-Sept.). Critical thresholds of weather elements were identified for achieving above average, average and below average yield for each ecology. The investigation could determine how different weather elements individually and collectively affect rice yield in different rice ecosystems of India. While a sudden increase in minimum temperature by 8-10 °C (> 30 °C) during reproductive period resulted in 40-50 per cent yield reduction at Mohanpur, a sudden decrease (< 20 °C) caused yield decline at Dapoli. The higher yields may be attributed to a significant difference in bright sunshine hours between reproductive phases of above-average and below-average yield years (ranging from 2.8 to 7.8 hours during P5 stages and 1.7 to 5.1 during P4 stages). Rice cultivar Swarna performed differently at various sowing dates in a location as well as across locations (6650 kg ha-1 at Dapoli to 1101 kg ha-1 at Samastipur). It was also found that across all locations, the above average yield could be associated with higher range of maximum temperature compared to that of below average yield. Principal component analysis explained 77 per cent of cumulative variance among the variables at first growth stage, whereas 70 per cent at second growth stage followed by 74 per cent and 66 per cent at subsequent growth stages. We found that coastal locations, in contrast to inland ones, could maximize the yield potential of the cultivar Swarna, due to the longer duration of days between panicle initiation to physiological maturity. We anticipate that the location-specific thresholds of weather factors will encourage rice production techniques that are climate resilient.
Physiological and transcriptomic analysis reveal the crucial factors in heat stress response of red raspberry ‘Polka’ seedlings
Authors: Guo Juanjuan , Zhang Ruiyu , Cheng Siqi , Fu Ziqian , Jia Peng , Luan Haoan , Zhang Xuemei , Qi Guohui , Guo Suping
Published: August 2023

With global climate warming, recurring extreme heat and high temperatures irreversibly damage plants. Raspberries, known for their nutritional and medicinal value, are in high demand worldwide. Thus, it is important to study how high-temperature stress (HTS) affects raspberries. The physiological and biochemical responses and molecular genetic mechanisms of raspberry leaves to different HTS treatments were investigated: mild high temperature at 35°C (HT35), severe high temperature at 40°C (HT40), and the control at room temperature of 25°C (CK). The physiological results suggested that leaves in both the 35°C and 40°C treatments showed maximum relative conductivity at 4 d of stress, increasing by 28.54% and 43.36%, respectively, compared to CK. Throughout the stress period (0–4 d), malondialdehyde (MDA) and soluble protein contents of raspberry leaves increased under HT35 and HT40 treatments, while soluble sugar content first decreased and then increased. Catalase (CAT) activity increased, superoxide dismutase (SOD) activity first increased and then decreased, and peroxidase (POD) activity gradually decreased. Photosynthetic and fluorescence responses of raspberry leaves showed the most severe impairment after 4 d of stress. Transcriptomics results revealed significant alterations in 42 HSP family genes, two SOD-related differentially expressed genes (DEGs), 25 POD-related DEGs, three CAT-related DEGs, and 38 photosynthesis-related DEGs under HTS. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly enriched in photosynthesis-antenna proteins, pentose and glucuronide interconversion, phenylpropane biosynthesis, and indole alkaloid biosynthesis. HTS induced excessive ROS accumulation in raspberry leaves, causing oxidative damage in plant cells and subsequently reducing photosynthesis in raspberry leaves. This reduction in photosynthesis, in turn, affects photosynthetic carbon fixation and starch and sucrose metabolism, which, combined with phenol propane biosynthesis, mitigates the HTS-induced damage.
A prospective study on body image disturbances during pregnancy and postpartum: the role of cognitive reappraisal
Authors: Spinoni Marta , Singh Solorzano Claudio , Grano Caterina
Published: August 2023

Background

During pregnancy, body size rapidly modifies over a relatively short period. Literature emphasizes the need to identify the factors that influence body image during peripartum as the extent of women’s adaptation to these changes has significant repercussions on both mother’s and newborn’s health. Emotion regulation strategies (i.e., expressive suppression and cognitive reappraisal) were linked to body image in the general and clinical population, but no studies were conducted in the peripartum. The present study aims to investigate the longitudinal impact of prepartum body image disturbances on postpartum body image disturbances and to evaluate the mediational role of emotional regulation strategies.

Methods

A total of 133 pregnant women completed a three-phase longitudinal study. Women answered online questionnaires during the second (T1) and the third (T2) trimesters of pregnancy, and at about 6 months postpartum (T3).

Results

Findings indicated that body image disturbances at T1 were a significant predictor of body image disturbances in the postpartum (1 year after the first assessment). Moreover, cognitive reappraisal measured at T2 partially mediated this relationship: body image disturbances in the second trimester of pregnancy were linked to less use of cognitive reappraisal in the third trimester of pregnancy, and this, in turn, was associated with worse body image disturbances at 6 months after birth.

Conclusion

Findings of this longitudinal study highlight the importance of assessing body image disturbances during pregnancy to early identify women at risk, and suggest cognitive reappraisal as a possible target intervention.
Modeling intentionality in the human brain
Authors: Giotakos Orestis
Published: August 2023

This paper is focusing on a rather neglected issue that concerns both aspects of philosophy and neurobiology in relation to the concept of intentionality. Intentionality is concerned with the ‘directedness’ or ‘aboutness’ of mental phenomena towards an object. Despite the fact that in philosophy both concepts of aboutness and directedness are conceptually identical with intentionality, a careful neuroscientific approach can demonstrate that these two phenomena represent two distinct conceptual and neurobiological aspects of intentionality with complementary functions. We described the interaction between a series of intentionality and pathogenetic psychobiological factors, the corresponding brain topography, and the resulting clinical manifestation and psychopathology. A permanent failure of intentionality dominates in psychosis, which includes an inappropriateness of the intentional object or connection, from the outset, or even from the prodromal phase of the disorder. Affective disorders may result from imprecise interoceptive prediction error signals, due to a confused identification of the intentional object. In suicidal patients there is an emotional intentionality failure, characterized by an absence of intentional object or a loss of conscious access to normal intentional objects. We may model an ‘intentional system’ as a higher order system, with a monitoring and regulatory role attributed to the brain and behavior. Also, we may consider mental disorders as the result of a radical disruption of intentionality, due to an inappropriateness or lack of the intentional object or due to an inappropriate connection in some points of the suggested brain pathways of intentionality.
Autism Spectrum Disorders in forensic psychiatric investigations–patterns of comorbidity and criminality
Authors: Hofvander Björn , Nilsson Thomas , Ståhlberg Ola , Claesdotter Emma , Moberg Patricia , Ahlbäck Klara , Hildebrand Karlén Malin
Published: August 2023

Background

There are contradictory research findings regarding whether individuals with Autism Spectrum Disorders (ASDs) are more or less likely to commit crimes. The aims of the current study were to: (1) Describe psychiatric and crime-related characteristics of a large group of offenders with ASD who had undergone a Forensic Psychiatric Investigation (FPI). (2) Identify clinical subgroups among this group of offenders. (3) Investigate associations between the identified clinical subgroups and (a) psychiatric comorbidity (b) types of crimes and (c) criminal responsibility.

Methods

The study cohort consists of all subjects (n = 831) who received an ASD-diagnosis at an FPI between 2002 and 2018 in Sweden. Descriptive and clinical, as well as crime related variables were obtained from the FPIs. Non-parametric (Pearson χ2, Fisher's exact and Mann-Whitney U-test) inferential statistics were used for analyses of between-group differences and effect sizes were reported. A Latent Class Analysis was used to identify homogeneous subgroups (or classes) from categorical characteristics.

Results

The cohort consisted of 708 men and 123 women, aged 18 to 74 yrs. Two-thirds (66.7%) of the cohort had at least one other psychiatric diagnosis, the most prevalent was substance use disorder (SUD). A severe mental disorder, equivalent to lack of criminal responsibility, was most often reported among offenders with a comorbid diagnosis of schizophrenia spectrum disorder. The most common type of crime was violent crime. Three person-oriented clinical subgroups were identified; (1) ASD with few other diagnoses; (2) ASD and very high levels of SUDs, plus moderate levels of other externalizing disorders and psychotic psychopathology and (3) ASD and moderate to high levels of personality disorders (other than ASPD) and SUDs.

Conclusion

Our results highlight the importance of all parts of the CJS to be prepared to handle offenders with ASD, often with high levels of additional psychiatric problems. Traditional approaches in treatment or other psychosocial interventions for ASD may need to be adapted to at least three general clinical profiles– one with mainly neurodevelopmental problems, one with a spectrum of externalizing problems and one with complex personality related difficulties.
How is caring for grandchildren associated with grandparents’ health: the mediating effect of internet use
Authors: Wang Jie , Gu Rongxing , Zhang Lanxi , Zhang Li
Published: August 2023

Objective

Prior studies showed mixed results of the association between grandchild care and grandparents’ health. This research focused on the mechanisms behind the above link by studying how internet use served as a mediator through which grandchild care has impacted grandparents’ health. The study aimed to draw implications to improve health of grandparents who offer care to grandchildren.

Methods

Using a sample of 16,829 grandparents aged 50 through 80 from the 2018 wave of China Health and Retirement Longitudinal Study (CHARLS), the study relied on the KHB method to conduct the analysis. Grandparental health was measured by self-rated health (SRH), instrumental activity of daily living (IADL), life satisfaction and depression.

Results

Overall, grandchild care had a positive effect on grandparental health. Those who engaged in grandchild care were more likely to use internet. In addition, internet use mediated the ways in which grandchild care impacted grandparents’ health. Interne use generally promoted the positive influence of grandparental caregiving on grandparents’ health. Specifically, the mediating effects of watching videos and chatting through the internet were most pronounced among urban grandmothers. The mediating effects of watching news were most noticeable among both urban grandmothers and grandfathers.

Conclusion

Internet use served as a mediator in the association between grandchild child care and grandparental health. Promoting internet usage may be an effective way reducing the negative impact of grandchild care on grandparents’ mental health. It could also increase the positive effect of caregiving on grandparents’ SRH and functional independence. The study also underscored the importance of taking rural–urban context and gender role into consideration when studying intergenerational caregiving and Chinese grandparents’ health.
The impact of disability-related deprivation on employment opportunity at the neighborhood level: does family socioeconomic status matter?
Authors: Qiu Ning , Jiang Yuxiao , Sun Zongyao , Du Mengbing
Published: August 2023

Introduction

Difficulties in attaining employment significantly contribute to socioeconomic poverty among individuals with disabilities. However, our understanding of how socioeconomic deprivation experienced by individuals and families with disabilities influences employment opportunities remains incomplete. This study aims to explore the relationship between index of disability-related multiple deprivation (IDMD) and employment opportunities (EMPO), while also investigating the role of family socioeconomic status (FSES) in shaping this relation.

Methods

This study explores the heterogeneous effects of IDMD, FSES, and the interaction between IDMD*FSES on EMPO among four disabled population groups categorized by IDMD and FSES.

Results

Results reveal that IDMD has a significant negative impact on EMPO, suggesting that persons with disabilities are confronted with a poverty trap resulting from the relationship between IDMD and EMPO. Furthermore, FSES demonstrates an effective moderating role in the IDMD-EMPO relationship, with the greatest impact observed among disabled population groups characterized by high IDMD and low FSES.

Discussion

The findings suggest that family-level support is crucial for vulnerable groups of disabled individuals to overcome the poverty trap, surpassing the reliance on individual-level assistance alone. This study supports a paradigm shift in comprehending disability-related deprivation by acknowledging its association with families, thereby presenting opportunities to enhance the welfare of people with disabilities.
A Neural-Network-Based Competition between Short-Lived Particle Candidates in the CBM Experiment at FAIR
Authors: Belousov Artemiy , Kisel Ivan , Lakos Robin
Published: August 2023

Fast and efficient algorithms optimized for high performance computers are crucial for the real-time analysis of data in heavy-ion physics experiments. Furthermore, the application of neural networks and other machine learning techniques has become more popular in physics experiments over the last years. For that reason, a fast neural network package called ANN4FLES is developed in C++, which will be optimized to be used on a high performance computer farm for the future Compressed Baryonic Matter (CBM) experiment at the Facility for Antiproton and Ion Research (FAIR, Darmstadt, Germany). This paper describes the first application of ANN4FLES used in the reconstruction chain of the CBM experiment to replace the existing particle competition between Ks-mesons and Λ-hyperons in the KF Particle Finder by a neural network based approach. The raw classification performance of the neural network reaches over 98% on the testing set. Furthermore, it is shown that the background noise was reduced by the neural network-based competition and therefore improved the quality of the physics analysis.
Sensitivity of Yponomeuta padella and Yponomeuta cagnagella (Lepidoptera: Yponomeutidae) to a Native Strain of Steinernema feltiae (Filipjev, 1934)
Authors: Kucharska Kornelia , Mazurkiewicz Anna , Tumialis Dorota , Florczak Lidia , Zajdel Barbara , Skrzecz Iwona
Published: August 2023

The larvae of ermine moths from the Yponomeutidae family (Lepidoptera) feed on a range of species and varieties of fruit and ornamental trees. Some species of this family pose a serious threat to the environment, mainly because of the significant defoliation they cause but also due to the widespread use of insecticides used to control them. This study was designed to assess the sensitivity of Yponomeuta padella and Yponomeuta cagnagella larvae and pupae to a native strain of Steinernema feltiae ZAG15 nematodes under laboratory conditions and to test the biological activity of these nematodes against the larvae and pupae of these species in field studies. The following doses were used in the laboratory tests: 50 IJs/insect (Petri dish tests) and 100 IJs/insect (container tests). Petri dish and container tests were performed at 20 °C and 60% humidity. Mortality of two stages (larvae and pupae) was determined 3 days after treatment. In the field trials, the nematodes were applied at the following doses: 4000 IJs/web for the caterpillars of Y. padella and Y. cagnagella and 1000 IJs/web for the pupae of Y. padella and Y. cagnagella (this corresponded to approximately 200 IJs/insect). Nematodes were applied using a 1 L hand sprayer and a lance. The efficacy of the application was assessed after seven days. The results of our study showed that the larvae (81.7%) and pupae (88.3%) of Y. padella had a greater susceptibility to entomopathogenic nematodes (EPNs) than those of Y. cagnagella (50% and 33.3%, respectively). However, our promising laboratory results did not translate into results in field trials, where the application of EPNs proved to be ineffective.
Comparing the Grain Yields and Other Properties of Old and New Wheat Cultivars
Authors: Bilandžija Darija , Zgorelec Željka , Galić Marija , Grubor Mateja , Krička Tajana , Zdunić Zvonimir , Bilandžija Nikola
Published: August 2023

Selecting cultivars with greater biomass results in higher yields and greater carbon sequestration. Storage of atmospheric carbon in the plant/soil pool contributes not only to food security but also to mitigating climate change and other agroecological benefits. The objective of this study was to determine: (1) grain, residue, and root biomass yields; (2) harvest indexes; (3) residue-to-product ratio; (4) root-to-shoot ratio; (5) biomass carbon and nitrogen contents; and (6) C:N ratios for two new and two old winter wheat cultivars. The greatest yield difference was found between old Srpanjka (the lowest) and new Kraljica (the highest) cultivar where grain, residue, root, and total biomass yield was higher by 38%, 91%, 71%, and 64%, respectively. Total biomass was composed of 40–47% grain, 10–11% roots, 32–36% stems + leaves, 9–11% chaff, and 1–2% spindle. The range of HI was 0.45–0.53, RPR 0.91–1.25, and R:S ratio 0.12–0.13. For all cultivars, positive carbon and negative nitrogen balance within the plant pool was determined. Still, root biomass and rhizodeposition carbon remain open questions for a better understanding of agroecosystems’ C dynamics.
An Overview of Biostimulants’ Effects in Saline Soils
Authors: Lakhdar Abdelbasset , Trigui Mohamed , Montemurro Francesco
Published: August 2023

The unsustainable use of natural resources and their overexploitation continue to be major threats to global agriculture development. This practice increases the abiotic stresses, resulting both in crop yield losses and soil degradation. Low productivity is often associated with salinized soil, which is caused by the toxic and osmotic effects of soluble salt accumulation and, consequently, lack of organic matter. Conversely, there is a need to improve the current crop productivity to meet the increasing food demands. Among the current methodologies proposed to increase plant resistance to abiotic stress, the utilization in crop production of plant biostimulants has been recently proposed. These are organic products mainly based on algae, microorganisms, fulvic and humic acids, proteins, and amino acids that improve physiological plant performance, leading to increased crop productivity. Among their positive benefits, the application of plant biostimulants can also reduce the usage of conventional chemical fertilizers. The aim of this work was to present the effects of different biostimulants on saline conditions. In particular, in this review, we report and critically discuss the most recent research dealing with the effects of the application of plant biostimulants both on crop growth and on plant salinity resistance.
The Influence of Heat Stress on Chicken Immune System and Mitigation of Negative Impacts by Baicalin and Baicalein
Authors: Zmrhal Vladimir , Svoradova Andrea , Venusova Eva , Slama Petr
Published: August 2023

Heat stress (HS) in poultry husbandry is an important stressor and with increasing global temperatures its importance will increase. The negative effects of stress on the quality and quantity of poultry production are described in a range of research studies. However, a lack of attention is devoted to the impacts of HS on individual chicken immune cells and whole lymphoid tissue in birds. Oxidative stress and increased inflammation are accompanying processes of HS, but with deleterious effects on the whole organism. They play a key role in the inflammation and oxidative stress of the chicken immune system. There are a range of strategies that can help mitigate the adverse effects of HS in poultry. Phytochemicals are well studied and some of them report promising results to mitigate oxidative stress and inflammation, a major consequence of HS. Current studies revealed that mitigating these two main impacts of HS will be a key factor in solving the problem of increasing temperatures in poultry production. Improved function of the chicken immune system is another benefit of using phytochemicals in poultry due to the importance of poultry health management in today’s post pandemic world. Based on the current literature, baicalin and baicalein have proven to have strong anti-inflammatory and antioxidative effects in mammalian and avian models. Taken together, this review is dedicated to collecting the literature about the known effects of HS on chicken immune cells and lymphoid tissue. The second part of the review is dedicated to the potential use of baicalin and baicalein in poultry to mitigate the negative impacts of HS on poultry production.
Structure–Activity Relationships of Cationic Lipidoids against Escherichia coli
Authors: Jennings James , Ašćerić Dunja , Malanovic Nermina , Pabst Georg
Published: August 2023

Membrane-active molecules provide a promising strategy to target and kill pathogenic bacteria. Understanding how specific molecular features drive interactions with membrane components and subsequently cause disruption that leads to antimicrobial activity is a crucial step in designing next-generation treatments. Here, we test a library of lipid-like compounds (lipidoids) against Gram-negative bacteria Escherichia coli to garner in-depth structure–activity relationships using antimicrobial assays. Modular lipidoid molecules were synthesized in high-throughput, such that we could analyze 104 compounds with variable combinations of hydrophobic tails and cationic headgroups. Antibacterial activity was strongly correlated to specific structural features, including tail hydrophobicity and headgroup charge density, and also to the overall molecular shape and propensity for self-assembly into curved liquid crystalline phases. Dye permeabilization assays showed that E. coli membranes were permeabilized by lipidoids, confirming their membrane-active nature. The reduced permeabilization, as compared to Gram-positive Bacillus subtilis, alludes to the challenge of permeabilizing the additional outer membrane layer of E. coli. The effect of headgroup solubility in gemini-type lipidoids was also demonstrated, revealing that a headgroup with a more hydrophilic spacer between amine groups had enhanced activity against B. subtilis but not E. coli. This provides insight into features enabling outer membrane penetration and governing selectivity between bacterial species.
Off-Label Use of Ceftazidime/Avibactam for the Treatment of Pan-Drug-Resistant Klebsiella pneumoniae in a Neonate: Case Report and Literature Review
Authors: Mangarov Iliya , Georgieva Ralitsa , Petkova Valentina , Nikolova Irina
Published: August 2023

Background: Klebsiella pneumoniae is among the most common Gram-negative bacteria isolated to neonatal intensive care units (NICU) and one of the leading causes of morbidity and mortality. The ceftazidime/avibactam (CAZ-AVI) combination is approved for infections caused by aerobic Gram-negative organisms. It is licensed for use in infants over 3 months old. There are no safety and efficacy data regarding the administration of CAZ-AVI to infants younger than 3 months, except for a few case reports. Case presentation: This report describes a severely intoxicated 24-day-old, full-term, male neonate transferred to NICU level III from a secondary maternity hospital due to the deterioration of his general condition. On day four of admission, blood culture revealed the pan-drug-resistant (PDR) K. pneumoniae ss. pneumoniae, susceptible only to CAZ-AVI, which thus represented the only treatment option. Off-label CAZ-AVI was administered intravenously as a salvage therapy. Conclusions: In healthcare settings, treating resistant K. pneumoniae presents serious challenges, especially in NICU patients. The off-label treatment with CAZ-AVI for 17 days was safe and effective in this one-month-old patient. A year later, the patient was healthy with normal cognitive development.
The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy
Authors: Avakh Asiyeh , Grant Gary D. , Cheesman Matthew J. , Kalkundri Tejaswini , Hall Susan
Published: August 2023

Pseudomonas aeruginosa (P. aeruginosa) poses a grave clinical challenge due to its multidrug resistance (MDR) phenotype, leading to severe and life-threatening infections. This bacterium exhibits both intrinsic resistance to various antipseudomonal agents and acquired resistance against nearly all available antibiotics, contributing to its MDR phenotype. Multiple mechanisms, including enzyme production, loss of outer membrane proteins, target mutations, and multidrug efflux systems, contribute to its antimicrobial resistance. The clinical importance of addressing MDR in P. aeruginosa is paramount, and one pivotal determinant is the resistance-nodulation-division (RND) family of drug/proton antiporters, notably the Mex efflux pumps. These pumps function as crucial defenders, reinforcing the emergence of extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains, which underscores the urgency of the situation. Overcoming this challenge necessitates the exploration and development of potent efflux pump inhibitors (EPIs) to restore the efficacy of existing antipseudomonal drugs. By effectively countering or bypassing efflux activities, EPIs hold tremendous potential for restoring the antibacterial activity against P. aeruginosa and other Gram-negative pathogens. This review focuses on concurrent MDR, highlighting the clinical significance of efflux pumps, particularly the Mex efflux pumps, in driving MDR. It explores promising EPIs and delves into the structural characteristics of the MexB subunit and its substrate binding sites.
The Effect of Enrichment with Sour-Cherry Extracts on Gluten-Free Snacks Developed by Novel 3D Technologies
Authors: Nikolaou Evgenia N. , Karvela Evangelia D. , Papadopoulou Argyri , Karathanos Vaios T.
Published: August 2023

Gluten-free formulations (GF) were utilized as food inks enriched with sour-cherry powder (SCP) and lyophilized extract (SCLE), and their physicochemical, rheological, and thermomechanical properties were evaluated with respect to different leavening conditions. Post-printing drying was also assessed in terms of texture, color, and phenolic substances. SCP and SCLE enrichment decreased lightness by 15% and increased red hue by almost 30%, mainly in yeast formulations. SC addition reduced pH by more than 12% for SCP in both leavening conditions and at 10% to 12% for SCLE, depending on leavening agents. The SCLE addition doubled dynamic moduli and complex viscosity magnitudes and increased hardness at 75.7% compared to the control for baking-powder formulations. SC enrichment, compared to the control, increased the phenolic sum to more than 90% (87% SCLE, 96% SCP) in yeast formulations, presenting lower values (almost 70%) for baking powder. Antioxidant activity in 3D-printed snacks was positively influenced by SC incorporation, depending on the drying and leavening treatment. Phenolic content, in terms of total phenolic sum, origin, and composition, possibly impacts the product’s antioxidant activity by depicting antagonistic or synergistic phenomena. Ultimately, 3D printing is feasible for producing functional GF snacks enriched with sour-cherry extracts.